TW202408527A - Treatment or prevention of hiv infection - Google Patents

Abstract

The present invention relates to the treatment or prevention of HIV infection using rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, to a subcutaneous injection device, and to a method of administering rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension with a subcutaneous injection device.

Description

Treating or preventing HIV infection (Part 2)

Cross-references to related applications

This application claims priority from U.S. Provisional Patent Application Nos. 63/342994, 63/342972, and 63/342979, respectively, filed on May 17, 2022, the disclosures of which are hereby incorporated by reference. It is incorporated herein as if fully set forth herein.

The present invention relates to the treatment or prevention of HIV infection using rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, a subcutaneous injection device, and a subcutaneous injection device. Methods of administering rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension.

Treatment of human immunodeficiency virus (HIV) infection, known as the cause of acquired immunodeficiency syndrome (AIDS), remains a major medical challenge.

Currently available oral therapies require administration at least once daily. Therefore, people infected with HIV are reminded of their HIV-positive status every day, and daily administration may also lead to the disclosure of their HIV-positive status. Daily dosing requires the storage and transportation of large or bulky pills, and there is still a risk of patients forgetting to take their daily dose, thereby failing to adhere to the prescribed dosing regimen. In addition to reducing the effectiveness of treatment, this also leads to the emergence of viral resistance.

One type of HIV drug commonly used in highly active antiretroviral therapy (HAART) is non-nucleoside reverse transcriptase inhibitor (NNRTI). Rilpivirine is a NNRTI antiretroviral drug used to treat HIV infection. Rilpivirine is a second-generation NNRTI that has higher efficacy and a reduced side effect profile than older NNRTIs. Rilpivirine activity is mediated by non-competitive inhibition of HIV-1 reverse transcriptase.

Rilpivirine not only shows significant activity against wild-type HIV, but also shows significant activity against many of its mutant variants. Rilpivirine, its pharmacological activity, and many procedures for its preparation have been described in WO 03/16306.

Rilpivirine is approved for the treatment of HIV infection and is commercially available as single agent tablets (EDURANT®), each tablet containing 25 mg of rilpivirine base equivalent. For once-daily oral administration, as well as single-lozenge regimens for once-daily oral administration (COMPLERA ^® , ODEFSEY ^® , JULUCA ^® ).

WO2007/147882 discloses the intramuscular or subcutaneous injection of a therapeutically effective amount of rilpivirine in the form of micro- or nanoparticles, rilpivirine having a surface modifier adsorbed to its surface; and a pharmaceutically acceptable aqueous carrier; wherein the rilpivirine active ingredient is suspended.

The combined administration of rilpivirine long-release suspension for injection and cabotegravir long-release suspension for injection has been approved, for example, in the United States and Canada as co-pack CABENUVA®, and in For example, EU approval is REKAMBYS®. These are the first antiretroviral drugs available in long-acting injectable formulations, intended for administration at intervals greater than one day.

There remains a need to provide effective methods for preventing HIV transmission or treating HIV infection that require infrequent administration, that is, administration every few months or more.

In a first aspect, a rilpivirine or a pharmaceutically acceptable salt thereof for treating or preventing HIV infection in a subject is provided, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a suspension in the form of micron or nanoparticles, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min, And wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about seven months.

In a second aspect, a method for treating or preventing HIV infection in a subject is provided, the method comprising administering to the subject a therapeutically effective amount of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in a suspension, which is administered by subcutaneous injection at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three to seven months.

In a third aspect, a use of rilpivirine or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing HIV infection in a subject is provided, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in the form of micro- or nanoparticles in a suspension, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered to the subject by subcutaneous injection at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at time intervals of about three months to about seven months.

In a fourth aspect, a subcutaneous medical injection device is provided, comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, The volume is greater than 3 mL and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or pharmaceutically acceptable salt and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and the suspension at about 0.1 mL/min to about 15 mL/min. The flow rate is driven out of the discharge nozzle.

In a fifth aspect, a method of administering a pharmaceutical composition using a hypodermic injection device is provided, the method comprising: inserting a discharge nozzle of the hypodermic injection device into the subcutaneous layer of a patient; and causing a driver of the hypodermic injection device to inject a A volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is driven from the container of the injection device and the volume of rilpivirine in the form of micron or nanoparticles in suspension is driven from the container of the injection device at a rate of about 0.1 mL/min to about 15 mL/min. The flow rate of the suspension driven from the discharge nozzle is greater than 3 mL and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months.

In a sixth aspect, a method for preparing a subcutaneous injection device for injection is provided, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof being in the form of micro- or nanoparticles in a suspension, and the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months.

In a seventh aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and to deliver the rilpivirine or the pharmaceutically acceptable salt to the patient at a rate of about 0.1 mL/min to about 15 mL/min of the suspension driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain therapeutic levels of the rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months. The kit may include an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of a subcutaneous medical injection device, or the container may be pre-filled with the volume. In one aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and to deliver the rilpivirine or the pharmaceutically acceptable salt to the patient at a rate of about 0.1 mL/min to about 15 mL/min of the suspension is driven out of the discharge nozzle; and a drug supply device, which contains a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt thereof in a patient for at least three months, and wherein the kit comprises an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the subcutaneous medical injection device.

In an eighth aspect, a subcutaneous medical injection device is provided, comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 μm to about 6 μm, a D _v 50 of about 1.5 μm to about 2 μm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and at a speed of about 0.1 A flow rate of the suspension of about 10 mL/min to about 15 mL/min is driven out of the discharge nozzle.

In a ninth aspect, a method for administering a drug using a subcutaneous injection device is provided, the method comprising: inserting a discharge nozzle of the subcutaneous injection device into the subcutaneous layer of a patient; and causing an actuator of the subcutaneous injection device to drive a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in a suspension from a container of the injection device and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min, wherein the micro- or nanoparticles have a D _v 90 of about 4 μm to about 6 μm, a D _v 50 of about 1.5 μm to about 2 μm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months.

In a tenth aspect, a method of preparing a subcutaneous injection device for injection is provided, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, about 1.5 µm to about 2 µm D _v 50, and a D _v 10 of about 300 nm to about 500 nm, and the volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months.

In an eleventh aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of Lipid in the form of micron or nanoparticles in suspension. Warin or a pharmaceutically acceptable salt thereof, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _{v 50 of about 1.5 µm to about 2 µm, and a D v} 50 of about 300 nm to about D _v 10 at 500 nm, a volume that is 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver The rilpivirine or pharmaceutically acceptable salt is delivered subcutaneously to the patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container at about 0.1 mL/min A flow rate of the suspension to about 15 mL/min is driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or its pharmaceutical counterpart in the form of micron or nanoparticles in the suspension. Acceptable salts, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm. , the volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months. The kit may comprise an introducer for introducing this volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of a subcutaneous medical injection device, or the container may be prefilled with this volume. In one aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine in the form of micron or nanoparticles in suspension or a pharmaceutically acceptable salt thereof, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D v 50 of about 300 nm to about 500 nm D _v 10, the volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or pharmaceutically acceptable salt subcutaneously delivering rilpivirine or a pharmaceutically acceptable salt to a patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container at about 0.1 mL/min to about A flow rate of the suspension of 15 mL/min is driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or its pharmaceutically acceptable form in the form of micron or nanoparticles in the suspension Salts, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the The volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months, and wherein the set includes a method for administering such volume of rilpivirine or An introducer for introducing a pharmaceutically acceptable salt thereof into the container of the subcutaneous medical injection device.

Rilpivirine

Rilpivirine (4-[[4-[[4-[(1E)-2-cyanovinyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]-amino ]-benzonitrile; TMC278) has the following structural formula:

"Rilpivirine" means rilpivirine having the structural formula shown above (that is, the free base form).

As used in the present invention, rilpivirine or its pharmaceutically acceptable salt is in the form of micron or nanoparticles in suspension, that is, rilpivirine or its pharmaceutically acceptable salt in suspension. Micron or nanoparticles of salts, especially micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof suspended in a pharmaceutically acceptable carrier (such as, for example, a pharmaceutically acceptable aqueous carrier) particle.

Pharmaceutically acceptable salts of rilpivirine refer to those in which the counter ion is pharmaceutically acceptable. Pharmaceutically acceptable salts are meant to include the therapeutically active non-toxic acid addition salt forms that rilpivirine is capable of forming. Such salt forms may be conveniently obtained by treating rilpivirine with appropriate acids, such as inorganic acids, such as hydrohalic acids, such as hydrochloric acid, hydrobromic acid, and the like; sulfuric acid; nitric acid; phosphoric acid and the like; or organic acids such as acetic acid, propionic acid, glycolic acid, 2-hydroxypropionic acid, 2-hydroxypropionic acid, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, malic acid , tartaric acid, 2-hydroxy-1,2,3-propanetricarboxylic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, 4-methyl-benzenesulfonic acid, cyclohexaneaminesulfonic acid, 2-hydroxybenzene Formic acid, 4-amino-2-hydroxybenzoic acid, and similar acids.

In a preferred embodiment, the rilpivirine or its pharmaceutically acceptable salt used in the present invention is rilpivirine.

Those skilled in the art will appreciate that the size of a micro- or nanoparticle should be below a maximum dimension above which administration by subcutaneous or intramuscular injection becomes impeded or even no longer possible. The maximum dimension is determined, for example, by limitations imposed by needle diameter or by the body's adverse reactions to large particles, or both.

In a preferred embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is in the form of nanoparticles.

Two embodiments of rilpivirine or pharmaceutically acceptable salts thereof with preferred particle sizes are contemplated herein.

In a first preferred particle size embodiment, the micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof have a D _v 90 of less than or about 2 μm. In this embodiment, the micron or nanoparticles may have a D _v 90 of about 100 nm to about 2 μm. In this embodiment, the micron or nanoparticles may have a D _v 90 of 200 nm to about 2 μm. In this embodiment, the micron or nanoparticles may have a D _v 90 of 300 nm to about 2 μm. In this embodiment, the micron or nanoparticles may have a D _v 90 of 400 nm to about 2 μm. In this embodiment, the micron or nanoparticles may have a D _v 90 of 500 nm to about 2 μm. Preferably, in this embodiment, the micro- or nanoparticles have a D _v 90 of 500 nm to about 1,600 nm, or a D _v 90 of 500 nm to about 1,000 nm, such as about 800 nm. More preferably, in this embodiment, the particles have a D _v 90 of about 500 nm to about 700 nm, even more preferably about 500 nm to about 650 nm, and most preferably about 525 nm to about 644 nm.

As used herein, the term "D _v 90" means the diameter below which 90% by volume of a population of particles are found. As used herein, the term "D _v 50" means the diameter below which 50% by volume of a population of particles are found. As used herein, the term "D _v 10" means the diameter below which 10% by volume of a population of particles are found.

In a first preferred particle size embodiment, the micro- or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof may have a D _v 50 of less than or about 1,000 nm. In this embodiment, the micro- or nanoparticles may have a D _v 50 of about 10 nm to about 1,000 nm. In this embodiment, the micro- or nanoparticles may have a D _v 50 of about 50 nm to about 700 nm. In this embodiment, the micro- or nanoparticles may have a D _v 50 of about 100 nm to about 600 nm. In this embodiment, the micro- or nanoparticles may have a D _v 50 of about 150 nm to about 500 nm. Preferably, in this embodiment, the micro- or nanoparticles have a D _v 50 of about 200 nm to about 500 nm.

In a first preferred particle size embodiment, the micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof may have a D _v 10 of less than or about 500 nm. In this embodiment, the micron or nanoparticles may have a D _v 10 of about 10 nm to about 500 nm. In this embodiment, the micron or nanoparticles may have a D _v 10 of about 25 nm to about 400 nm. In this embodiment, the micron or nanoparticles may have a D _v 10 of about 50 nm to about 300 nm. In this embodiment, the micron or nanoparticles may have a D _v 10 of about 50 nm to about 200 nm. Preferably, in this embodiment, the micron or nanoparticles have a D _v 10 of about 75 nm to about 200 nm.

Preferably, in this embodiment, the micro- or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof have a D _v 90 of about 500 nm to about 1,600 nm, a D _v 50 of about 200 nm to about 500 nm, and a D _v 10 of about 75 nm to about 200 nm.

Alternatively, the micro- or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof have a D _v 90 of about 500 nm to about 1,000 nm, a D _v 50 of about 200 nm to about 500 nm, and a D _v 10 of about 75 nm to about 200 nm.

Alternatively, the particles have _{a Dv90} of about 500 nm to about 700 nm, a _Dv50 of about 200 nm to about 500 nm, and _{a Dv10} of about 75 nm to about 200 nm.

In a second preferred particle size embodiment, the micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof may have a D _v 90 of about 1 µm to about 10 µm. In this embodiment, the micron or nanoparticles may have a D _v 90 of about 2 µm to about 9 µm. In this embodiment, the micron or nanoparticles may have a D _v 90 of about 3 µm to about 8 µm. In this embodiment, the micron or nanoparticles may have a D _v 90 of about 3 µm to about 7 µm. Preferably, in this embodiment, the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm. Optimally, in this embodiment, the particles have a D _v 90 of about 5 µm to about 6 µm, such as about 5 µm or about 6 µm.

In a second preferred particle size embodiment, the micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof have a _Dv50 of less than or about 3 µm. In this embodiment, the micron or nanoparticles may have a _Dv50 of less than about 2.5 µm. In this embodiment, the micron or nanoparticles may have a _Dv50 of about 1 µm to about 2.5 µm. In this embodiment, the micron or nanoparticles may have a _Dv50 of about 1.2 µm to about 2.2 µm. Preferably, in this embodiment, the micron or nanoparticles have a _Dv50 of about 1.5 µm to about 2 µm.

In a second preferred particle size embodiment, the micro- or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof may have a D _v 10 of less than or about 1000 nm. In this embodiment, the micro- or nanoparticles may have a D _v 10 of about 10 nm to about 1000 nm. In this embodiment, the micro- or nanoparticles may have a D _v 10 of about 100 nm to about 700 nm. In this embodiment, the micro- or nanoparticles may have a D _v 10 of about 200 nm to about 600 nm. Preferably, in this embodiment, the micro- or nanoparticles have a D _v 10 of about 300 nm to about 500 nm.

Preferably, in this embodiment, the micro- or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm.

As used herein, D _v 10, D _v 50, and D _v 90 are determined by conventional laser diffraction techniques, such as in accordance with ISO 13320:2009.

Laser diffraction relies on the principle that particles will scatter light at angles that depend on changes in size of the particles, and a collection of particles will produce a pattern of scattered light defined by intensity and angle, which can be correlated to the particle size distribution. Many laser diffraction instruments are commercially available for rapid and reliable determination of particle size distribution. For example, particle size distribution can be measured by a conventional Malvern Mastersizer™ 3000 particle size analyzer from Malvern Instruments. The Malvern Mastersizer™ 3000 Particle Size Analyzer operates by projecting a laser beam of helium-neon gas through a transparent tank containing particles of interest suspended in an aqueous solution. The light striking the particles is scattered through an angle inversely proportional to the particle size, and an array of light detectors measures the light intensity at several predetermined angles, and the measured intensity at different angles is processed by a computer using standard theoretical principles to determine the particle size distribution. . Laser diffraction values can be obtained using wet dispersions of particles in distilled water.

Other methods commonly used in the art to measure D _v 10, D _v 50, and D _v 90 include disk centrifugation, scanning electron microscopy (SEM), sedimentation field flow fractionation, and photon correlation spectroscopy.

In one embodiment, the suspension contains about 100 to about 500 mg/mL rilpivirine or a pharmaceutically acceptable salt thereof. In one embodiment, the suspension contains about 150 to about 450 mg/mL rilpivirine or a pharmaceutically acceptable salt thereof. In one embodiment, the suspension contains about 200 to about 400 mg/mL rilpivirine or a pharmaceutically acceptable salt thereof. In one embodiment, the suspension contains about 250 to about 350 mg/mL rilpivirine or a pharmaceutically acceptable salt thereof, such as about 300 mg/mL, especially 300 mg/mL rilpivirine.

In one embodiment, the micro- or nanoparticles have one or more surface modifiers adsorbed to their surface.

The surface modifier can be selected from known organic and inorganic pharmaceutical excipients, including various polymers, low molecular weight oligomers, natural products, and surfactants. Specific surface modifiers that can be used in the present invention include non-ionic and anionic surfactants. Representative examples of surface modifiers include gelatin, casein, lecithin, salts or acid forms of negatively charged phospholipids (such as phosphatidylglycerol, phosphatidyl inosite, phosphatidyl serine, phosphoric acid, and salts thereof, such as alkaline metal salts, such as sodium salts thereof, such as sodium egg phosphatidylglycerol, such as the product available under the trade name Lipoid™ EPG), gum arabic, stearic acid, benzalkonium chloride, polyoxyethylene alkyl ethers (such as macrogol ethers, such as cetomacrogol ether 1000), and polyoxyethylene alkyl ethers. 1000)), polyoxyethylene castor oil derivatives; polyoxyethylene stearate, colloidal silica, sodium lauryl sulfate, sodium carboxymethyl cellulose, bile salts (such as sodium taurocholate, sodium deoxytaurocholate, sodium deoxycholate); methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, polyvinyl alcohol (PVA), poloxamer (such as Pluronic™ F68, F108, and F127, which are block copolymers of ethylene oxide and propylene oxide); tyloxapol; vitamin E-TGPS (alpha-tocopheryl polyethylene glycol succinate, particularly alpha-tocopheryl polyethylene glycol 1000 succinate); poloxamines, such as Tetronic™ 908 (T908), which are tetrafunctional block copolymers derived from the sequential addition of ethylene oxide and propylene oxide to ethylenediamine; dextran; lecithin; dioctyl sodium sulfosuccinate, such as the product sold under the trade name Aerosol OT™ (AOT); sodium lauryl sulfate (Duponol™ P); Triton™ X-200; polyoxyethylene sorbitan fatty acid esters (Tweens™ 20, 40, 60, and 80); sorbitan esters of fatty acids (Span™ 20, 40, 60, and 80 or Arlacel™ 20, 40, 60, and 80); polyethylene glycol (such as those sold under the trade names Carbowax™ 3550 and 934); sucrose stearate and sucrose distearate mixtures, such as those sold under the trade names Crodesta™ F110 or Crodesta™ SL-40; hexyldecyltrimethylammonium chloride (CTAC); polyvinylpyrrolidone (PVP). If desired, two or more surface modifiers may be used in combination.

In one embodiment, the surface modifier is selected from poloxamers, α-tocopherol polyethylene glycol succinate, polyoxyethylene sorbitan fatty acid esters, and salts or acid forms of negatively charged phospholipids. In one embodiment, the surface modifier is selected from Pluronic™ F108, vitamin E TGPS (α-tocopherol polyethylene glycol succinate, particularly α-tocopherol polyethylene glycol 1000 succinate), polyoxyethylene sorbitan fatty acid esters (such as Tween™ 80), and phosphatidylglycerol, phosphatidyl inositol, phosphatidyl serine, phosphoric acid, and salts thereof (such as alkaline metal salts, such as sodium salts thereof, such as sodium egg phosphatidylglycerol, such as products available under the trade name Lipoid™ EPG).

In one embodiment, the surface modifier is moxamer, specifically Pluronic™ F108. Pluronic™ F108 corresponds to poloxamer 338 and is a polyoxyethylene, polyoxypropylene block copolymer, which generally conforms to the formula HO-[CH ₂ CH ₂ O] _x -[CH(CH ₃ )CH ₂ O] _y -[CH ₂ CH ₂ O] _z -H, where the average values of x, y, and z are 128, 54, and 128 respectively. Other commercial names for poloxamer 338 are Hodag Nonionic™ 1108-F and Synperonic™ PE/F108. In one embodiment, the surface modifying agent includes a combination of polyoxyethylene sorbitan fatty acid ester and phospholipid glycerol salt (especially sodium glyceryl egg phospholipid).

In one embodiment, the relative amount (w/w) of rilpivirine or its pharmaceutically acceptable salt to the surface modifier is about 1:2 to about 20:1, particularly about 1:1 to about 10:1, such as about 4:1 to about 6:1, preferably about 6:1. The surface modifier is preferably a poloxamer, such as poloxamer 338.

In one embodiment, the micron or nanoparticles of the present invention comprise rilpivirine or a pharmaceutically acceptable salt thereof as defined herein and one or more surface modifiers as defined herein, wherein rilpivir The amount of Lin or its pharmaceutically acceptable salt is at least about 50% by weight of micron or nanoparticles, at least about 80% by weight of micron or nanoparticles, at least about 85% by weight of micron or nanoparticles, micron or At least about 90% by weight of nanoparticles, at least about 95% by weight of micron or nanoparticles, or at least about 99% by weight of micron or nanoparticles, especially between 80% and 90% by weight of micron or nanoparticles %, or between 85% and 90% by weight of micron or nanoparticles.

In one embodiment, the suspension includes a pharmaceutically acceptable carrier in which micron or nanoparticles of rilpivirine or a pharmaceutically acceptable salt thereof are suspended. Pharmaceutically acceptable aqueous carriers include sterile water, such as water for injection, optionally mixed with other pharmaceutically acceptable ingredients. The latter includes any ingredients used in injectable formulations. These ingredients may be selected from one or more of suspending agents, buffers, pH adjusters, preservatives, isotonic agents, surface modifiers, chelating agents, and similar ingredients. In one embodiment, the ingredients are selected from one or more of suspending agents, buffers, pH adjusters, and optionally preservatives and isotonic agents. Particular ingredients may act as two or more of these agents simultaneously, for example acting as a preservative and a buffering agent, or acting as a buffering agent and an isotonic agent. In one embodiment, the components are selected from one or more of buffers, pH adjusters, isotonic agents, chelating agents, and surface modifying agents. In one embodiment, the components are selected from one or more of buffers, pH adjusters, isotonic agents, and chelating agents.

In one embodiment, the suspension further comprises a buffer and/or a pH adjuster. Suitable buffers and pH adjusters should be used in an amount sufficient to render the dispersion neutral to very slightly alkaline (up to pH 8.5), preferably in the pH range of 7 to 7.5. Specific buffers are salts of weak acids. The buffer and pH adjuster that can be added can be selected from tartaric acid, citric acid, glycine, sodium lactate/lactic acid, ascorbic acid, sodium citrate/citric acid, sodium acetate/acetic acid, sodium bicarbonate/carbonic acid, sodium succinate/succinic acid, sodium benzoate/benzoic acid, sodium phosphate, tris(hydroxymethyl)amino-methane, sodium bicarbonate/sodium carbonate, ammonium hydroxide, benzenesulfonic acid, Sodium benzoate/benzoic acid, diethanolamine, delta-gluconolactone, hydrochloric acid, hydrogen bromide, lysine, methanesulfonic acid, monoethanolamine, sodium hydroxide, tromethamine, gluconic acid, glyceric acid, gluratic acid, glutamine, ethylenediaminetetraacetic acid (EDTA), triethanolamine, including mixtures thereof. In one embodiment, the buffer is a sodium phosphate buffer, such as sodium dihydrogen phosphate monohydrate. In one embodiment, the pH adjuster is sodium hydroxide.

In one embodiment, the suspension additionally contains a preservative. Preservatives include antimicrobials and antioxidants, which may be selected from the group consisting of: benzoic acid, benzyl alcohol, butylated hydroxymethoxybenzene (BHA), dibutylated hydroxytoluene (BHT), chlorobutanol ( chlorbutol), gallate, hydroxybenzoate, EDTA, phenol, chlorocresol, m-cresol, benzethonium chloride, myristyl-γ-methylpyridinium chloride ( myristyl-γ-piccolinium chloride), phenylmercuric acetate, and thimerosal. Free radical scavengers include BHA, BHT, vitamin E, and ascorbyl palmitate, and mixtures thereof. Oxygen scavengers include sodium ascorbate, sodium sulfite, L-cysteine, acetyl cysteine, methionine, thioglycerol, acetone sodium bisulfite, isoascorbic acid, and hydroxypropylcyclodextrin . Chelating agents include sodium citrate, sodium EDTA, citric acid, and malic acid. In one embodiment, the chelating agent is citric acid, such as citric acid monohydrate.

In one embodiment, the suspension further comprises an isotonic agent. An isotonic agent (isotonizing agent/isotonifier) may be present to ensure the isotonicity of the pharmaceutical composition of the present invention, and includes sugars such as glucose, dextrose, sucrose, fructose, trehalose, lactose; polyhydric sugar alcohols, preferably tribasic or higher sugar alcohols such as glycerol, erythritol, arabitol, xylitol, sorbitol, and mannitol. Alternatively, sodium chloride, sodium sulfate, or other suitable inorganic salts may be used to make the solution isotonic. These isotonic agents may be used alone or in combination. The suspension conveniently comprises 0 to 10% (w/v), in particular 0 to 6% isotonic agent. Because electrolytes can affect colloid stability, nonionic isotonic agents such as glucose and mannitol are of concern.

In one embodiment, each administration comprises up to about 150 mL of a suspension described herein. In another embodiment, each administration comprises about 3 mL to about 150 mL of a suspension. In another embodiment, each administration comprises about 3 mL to about 100 mL of a suspension. In another embodiment, each administration comprises about 3 mL to about 15 mL of a suspension. In another embodiment, each administration comprises about 5 mL to about 25 mL of a suspension. In another embodiment, each administration comprises about 6 mL to about 20 mL of a suspension. In another embodiment, each administration comprises about 6 mL to about 18 mL of a suspension. In another embodiment, each administration comprises about 6 mL to about 15 mL of a suspension. In another embodiment, each administration comprises about 6 mL to about 12 mL of a suspension. In another embodiment, each administration comprises about 9 mL to about 18 mL of suspension. In another embodiment, each administration comprises about 9 mL to about 15 mL of suspension. In another embodiment, each administration comprises about 9 mL to about 12 mL of suspension. In another embodiment, each administration comprises about 8 mL to about 10 mL of suspension. In another embodiment, each administration comprises about 3 mL of suspension. In another embodiment, each administration comprises about 4 mL of suspension. In another embodiment, each administration comprises about 5 mL of suspension. In another embodiment, each administration comprises about 6 mL of suspension. In another embodiment, each administration comprises about 7 mL of suspension. In another embodiment, each administration comprises about 8 mL of suspension. In another embodiment, each administration comprises about 9 mL of suspension. In another embodiment, each administration comprises about 12 mL of suspension. In another embodiment, each administration comprises about 15 mL of suspension. In another embodiment, each administration comprises about 18 mL of suspension.

In one embodiment, for the treatment of HIV infection, the dose to be administered can be calculated based on about 300 mg to about 1200 mg/month, or about 350 mg to about 900 mg/month. Preferably, the dose to be administered can be calculated based on about 350 mg to about 550 mg/month, or about 400 mg to about 500 mg/month, or 450 mg/month. Alternatively, the dose to be administered can be calculated based on about 500 mg to about 700 mg/month, or about 550 mg to about 650 mg/month, or 600 mg/month. The dose for other dosing regimens can be easily calculated by multiplying the monthly dose by the number of months between each administration. For example, when the dose is 450 mg/month, when the time interval between each administration is 3 months, the dose to be administered for each administration is 1350 mg, when the time interval between each administration is 4 months, the dose to be administered for each administration is 1800 mg, when the time interval between each administration is 5 months, the dose to be administered for each administration is 2250 mg, when the time interval between each administration is 6 months, the dose to be administered for each administration is 2700 mg, and when the time interval between each administration is 7 months, the dose to be administered for each administration is 3150 mg. For example, when the dosage is 600 mg/month, when the time interval between each administration is 3 months, the dose to be administered for each administration is 1800 mg, when the time interval between each administration is 4 months, the dose to be administered for each administration is 2400 mg, when the time interval between each administration is 5 months, the dose to be administered for each administration is 3000 mg, when the time interval between each administration is 6 months, the dose to be administered for each administration is 3600 mg, and when the time interval between each administration is 7 months, the dose to be administered for each administration is 4200 mg. The indicated "mg" corresponds to mg of rilpivirine. Therefore, for example, 1 mg of rilpivirine corresponds to 1.1 mg of rilpivirine hydrochloride.

In one embodiment, for the treatment of HIV infection, the dose to be administered may be calculated based on about 300 mg to about 1200 mg/4 weeks (28 days), or about 350 mg to about 900 mg/4 weeks (28 days). Preferably, the dosage to be administered may be based on about 350 mg to about 550 mg/4 weeks (28 days), or about 400 mg to about 500 mg/4 weeks (28 days), or 450 mg/4 weeks (28 days). )calculate. Alternatively, the dosage to be administered may be based on about or about 500 mg to about 700 mg/4 weeks (28 days), or about 550 mg to about 650 mg/4 weeks (28 days), or 600 mg/4 weeks (28 days). days) calculation. Dosage for other dosing regimens can be readily calculated by multiplying the weekly or daily dose by the number of weeks between administrations. For example, when the dose is 450 mg/4 weeks, and the time interval between administrations is 12 weeks, the dose to be administered for each administration is 1350 mg, and the time interval between administrations is 1350 mg. In the case of 16 weeks, the dose to be administered for each administration is 1800 mg. In the case of 20 weeks between administrations, the dose to be administered for each administration is 2250 mg. If the time interval between each administration is 24 weeks, the dose to be administered for each administration is 2700 mg, and if the time interval between each administration is 28 weeks, the dose to be administered for each administration is 2700 mg. 3150 mg. The "mg" indicated corresponds to mg of rilpivirine (that is, rilpivirine in its free base form). Thus, as an example, 1 mg of rilpivirine (that is, rilpivirine in its free base form) corresponds to 1.1 mg of rilpivirine hydrochloride.

In one embodiment, a suspension of rilpivirine or a pharmaceutically acceptable salt thereof as described herein is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. . In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension from about 0.25 mL/min to about 9 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension from about 0.3 mL/min to about 6 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension from about 0.5 mL/min to about 3 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension from about 0.5 mL/min to about 2 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 9 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 6 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 3 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 2 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 1 mL/min. In another embodiment, the suspension of rilpivirine is administered by subcutaneous injection at a flow rate of the suspension of about 0.5 mL/min.

In some embodiments, the flow rate is constant throughout the administration, for example, the flow rate varies no more than ±10%, or no more than ±5% throughout the administration.

In one embodiment, the desired flow rate is achieved by administering a suspension of rilpivirine or a pharmaceutically acceptable salt thereof as described herein by subcutaneous injection using a subcutaneous medical injection device that provides a constant flow rate, such as an on-body injection device, an off-body injection device, or a handheld injection device. Suitable subcutaneous medical injection devices are further discussed herein. In one embodiment, a suspension of rilpivirine or a pharmaceutically acceptable salt thereof as described herein is administered by using a B. Braun Perfusor syringe pump.

In one embodiment, a suspension of rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection into a single injection site.

In one embodiment, each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month, rilpivirine is administered by subcutaneous injection at a flow rate of about 0.5 mL/min to about 6 mL/min of suspension, and the volume of suspension administered is about 6 mL to 12 mL. Preferably, rilpivirine is administered intermittently at intervals of six months. Preferably, rilpivirine is administered at a constant rate.

In one embodiment, each administration of rilpivirine is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month, rilpivirine is administered by subcutaneous injection at a flow rate of about 0.5 mL/min to about 3 mL/min of suspension, and the volume of suspension administered is about 8 mL to 10 mL. Preferably, rilpivirine is administered intermittently at intervals of six months. Preferably, rilpivirine is administered at a constant rate.

In a preferred embodiment, each administration of rilpivirine is calculated based on a dose of about 450 mg/month of rilpivirine, which is administered by subcutaneous injection at a rate of about 0.1 mL/min to about 2 The flow rate of the suspension in mL/min was administered at six-month intervals, and the volume of the suspension administered was approximately 9 mL. Preferably, rilpivirine is administered at a constant rate.

In the case of preventing HIV infection, each administration of rilpivirine or a pharmaceutically acceptable salt thereof may comprise the same dosage as the therapeutic administration as described above.

In one embodiment, the amount of rilpivirine or a pharmaceutically acceptable salt thereof used in the pharmaceutical composition is such that the plasma concentration of rilpivirine in a subject is maintained at a level above about 12 ng/mL, preferably in the range of about 12 ng/mL to about 100 ng/mL, more preferably about 12 ng/mL to about 50 ng/mL, for at least 3 months after administration, or at least 4 months after administration, or at least 5 months after administration, or at least 6 months after administration, or at least 7 months after administration. In a preferred embodiment, the amount of rilpivirine or a pharmaceutically acceptable salt thereof used in the pharmaceutical composition is such that the plasma concentration of rilpivirine in a subject is maintained at a level of 12 ng/mL to 100 ng/mL for at least 6 months.

In a specific embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as micro- or nanoparticles in a suspension and administered, wherein the formulation comprises the following components: Rilpivirine or a pharmaceutically acceptable salt thereof, in particular rilpivirine; A surface modifier as defined herein, in particular poloxamer 338; An isotonic agent, in particular glucose monohydrate; A buffer, in particular sodium dihydrogen phosphate; A chelating agent, in particular citric acid monohydrate; A pH adjusting agent, in particular sodium hydroxide; and Water, in particular water for injection.

In another specific embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as micro- or nanoparticles in a suspension and administered, wherein the formulation comprises the following components: rilpivirine or a pharmaceutically acceptable salt thereof, in particular rilpivirine; poloxamer 338; glucose monohydrate; sodium dihydrogen phosphate; citric acid monohydrate; sodium hydroxide; and water, in particular water for injection.

In one embodiment, the aqueous suspension may comprise by weight, based on the total volume of the suspension: (a) 3% to 50% (w/v), or 10% to 40% (w/v), or 10% to 30% (w/v) rilpivirine or its pharmaceutically acceptable salt ;especially rilpivirine; (b) 0.5% to 10% (w/v), or 0.5% to 5% (w/v), or 0.5% to 2% (w/v) surface modifiers; especially Poloxamer 338 ; (c) 0% to 10% (w/v), or 0% to 5% (w/v), or 0% to 2% (w/v), or 0% to 1% (w/v) one or more buffers; in particular sodium dihydrogen phosphate; (d) 0% to 10% (w/v), or 0% to 6% (w/v), or 0% to 5% (w/v), or 0% to 3% (w/v), or 0% to 2% (w/v) isotonic agents; especially glucose monohydrate; (e) 0% to 2% (w/v), or 0% to 1% (w/v), or 0% to 0.5% (w/v), or 0% to 0.1% (w/v) pH adjusters; especially sodium hydroxide; (f) 0% to 2% (w/v), or 0% to 1% (w/v), or 0% to 0.5% (w/v), or 0% to 0.1% (w/v) Chelating agents; especially citric acid monohydrate; (g) 0% to 2% (w/v) preservatives; and (h) Water for injection in an amount sufficient to add to 100%.

In one embodiment, the aqueous suspension may comprise by weight, based on the total volume of the suspension: (a) 3% to 50% (w/v), or 10% to 40% (w/v), or 10% to 30% (w/v) rilpivirine or its pharmaceutically acceptable salt ;especially rilpivirine; (b) 0.5% to 10% (w/v), or 0.5% to 5% (w/v), or 0.5% to 2% (w/v) surface modifiers; especially Poloxamer 338 ; (c) 0% to 10% (w/v), or 0% to 5% (w/v), or 0% to 2% (w/v), or 0% to 1% (w/v) one or more buffers; in particular sodium dihydrogen phosphate; (d) 0% to 10% (w/v), or 0% to 6% (w/v), or 0% to 5% (w/v), or 0% to 3% (w/v), or 0% to 2% (w/v) isotonic agents; especially glucose monohydrate; (e) 0% to 2% (w/v), or 0% to 1% (w/v), or 0% to 0.5% (w/v), or 0% to 0.1% (w/v) pH adjusters; especially sodium hydroxide; (f) 0% to 2% (w/v), or 0% to 1% (w/v), or 0% to 0.5% (w/v), or 0% to 0.1% (w/v) Chelating agents; especially citric acid monohydrate; and (g) Water for injection in an amount sufficient to add to 100%.

In a specific embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is formulated into a suspension of micro- or nanoparticles (and administered), wherein the suspension comprises the following components: (a) rilpivirine (300 mg); (b) poloxamer 338 (50 mg); (c) glucose monohydrate (19.25 mg); (d) sodium dihydrogen phosphate (2.00 mg); (e) citric acid monohydrate (1.00 mg); (f) sodium hydroxide (0.866 mg); and (g) water for injection (up to 1 mL). Use of rilpivirine or a pharmaceutically acceptable salt thereof in the present invention

Rilpivirine or a pharmaceutically acceptable salt thereof for treating or preventing HIV infection in a subject, wherein the rilpivirine or the pharmaceutically acceptable salt thereof is in the form of micro- or nanoparticles in a suspension, wherein the rilpivirine or the pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min, and wherein the rilpivirine or the pharmaceutically acceptable salt thereof is administered intermittently at time intervals of about three months to about seven months.

Accordingly, the uses of rilpivirine for treatment or prophylaxis described herein involve multiple administrations of rilpivirine or a pharmaceutically acceptable salt thereof, and the administration of rilpivirine or a pharmaceutically acceptable salt thereof The time interval between the salt and the subsequent administration of rilpivirine or a pharmaceutically acceptable salt thereof (i.e., the dosing interval) is from about three months to about seven months. That is, rilpivirine according to the present invention or a pharmaceutically acceptable salt thereof is administered to a subject as described herein, and then, after a period of three to seven months, rilpivirine according to the present invention is administered. Wareing or a pharmaceutically acceptable salt thereof is administered again to a subject as defined herein.

In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof for treating or preventing HIV infection in a subject, wherein rilpivirine or a pharmaceutically acceptable salt thereof is in the form of micro- or nanoparticles in a suspension, wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of about 0.1 mL/min to about 15 mL/min of the suspension, and wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about two years. In one embodiment, the interval is about three months to about eighteen months. In one embodiment, the interval is about three months to about one year. In one embodiment, the interval is about three months to about seven months. In one embodiment, the interval is about three months to about six months. In one embodiment, the time interval is about six months to about one year. In one embodiment, the time interval is about one year. In one embodiment, the time interval is about three months. In one embodiment, the time interval is about six months.

As used herein in connection with the methods and uses for treatment or prevention described herein, the term "is administered/are administered" may encompass the term "is to be administered/are to be administered".

In a preferred embodiment, the subject is a human. More preferably, the subject is an adult infected with HIV. Most preferably, the subject is an adult infected with HIV who has been virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable retroviral regimen for, for example, at least 20 weeks.

In one embodiment, the time interval is about three months to about two years. In one embodiment, the time interval is about three months to about eighteen months. In one embodiment, the time interval is about three months to about one year. In one embodiment, the time interval is about three months to about six months. In one embodiment, the time interval is about six months to about one year. In one embodiment, the time interval described herein is about one year. In one embodiment, the time interval described herein is about three months to about seven months. In one embodiment, the time interval described herein is about three months. In one embodiment, the time interval described herein is about four months. In one embodiment, the time interval described herein is about five months. In one embodiment, the time interval described herein is about six months. In one embodiment, the time interval described herein is about seven months.

Rilpivirine or its pharmaceutically acceptable salt of the present invention is used to treat or prevent HIV infection in a subject. Rilpivirine or a pharmaceutically acceptable salt thereof is administered in a therapeutically effective amount. "Therapeutically effective amount" means an amount sufficient to provide a therapeutic effect.

In a specific embodiment, rilpivirine or a pharmaceutically acceptable salt thereof for use in the present invention is rilpivirine, and rilpivirine is used to treat HIV infection in a subject as described herein, The suspension includes a pharmaceutically acceptable aqueous carrier, and rilpivirine is suspended in the aqueous carrier in the form of micron or nanoparticles. Preferably, the micron or nanoparticles have a diameter of about 500 nm to about 1,600 nm. D _v 90, a D _v 50 of about 200 nm to about 500 nm, and a D _v 10 of about 75 nm to about 200 nm, or micron or nanoparticles having a D _v 90 of about 4 µm to about 6 µm, about 1.5 D _v 50 from µm to about 2 µm, and D _v 10 from about 300 nm to about 500 nm, and preferably the surface modifier (such as poloxamer 338) is adsorbed to the surface of the micron or nanoparticles .

In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof of the present invention is used in a method for treating or preventing HIV type 1 (HIV-1) infection in a subject, one of which is described herein. Embodiments relate to the use of rilpivirine, or a pharmaceutically acceptable salt thereof, as defined herein, for the treatment or prevention of HIV type 1 (HIV-1) infection in a subject.

As used herein, the term "treatment of HIV infection" relates to the treatment of a subject infected with HIV. The term "treatment of HIV infection" also relates to the treatment of diseases associated with HIV infection (such as AIDS) or other conditions associated with HIV infection, including thrombocytopenia, Kaposi's sarcoma, and infections of the central nervous system characterized by progressive demyelination leading to dementia and symptoms such as progressive dysarthria, ataxia, and disorientation; and other conditions also associated with HIV infection, such as peripheral neuropathy, progressive generalized lymphadenopathy (PGL), and AIDS-related complex (ARC).

As used herein, the term "prevention of HIV infection" refers to preventing or preventing a subject (who is not infected with HIV) from becoming infected with HIV. The source of infection can be of various kinds, it can be an HIV-containing substance, especially HIV-containing body fluids (such as blood or semen), or it can be another subject infected with HIV. Prevention of HIV infection is about preventing the spread of the virus from HIV-containing substances or from HIV-infected individuals to uninfected persons, or about preventing the entry of the virus into the bodies of uninfected persons. The HIV virus can be transmitted by any known cause of HIV transfer, such as through sexual transmission or through blood contact with an infected subject, such as a health care worker providing care to an infected subject. Transfer of HIV can also occur through contact with HIV-infected blood, such as when processing blood samples or transfusing blood. It can also occur through contact with infected cells, such as when conducting laboratory experiments with HIV-infected cells.

The term "treatment of HIV infection" means treatment that reduces the viral load of HIV (expressed as the number of viral RNA copies in a specified volume of serum). The more effective the treatment, the lower the viral load. Preferably, the viral load should be reduced to the lowest possible level, such as less than about 200 copies/mL, especially less than about 100 copies/mL, and more particularly less than 50 copies/mL. , if possible, below the detection limit of the virus. A reduction in viral load of one, two, or even three orders of magnitude (eg, a reduction of about 10 to about 10 ² , or more, such as about 10 ³ ) is an indicator of the effectiveness of the treatment. Another parameter that measures the effectiveness of HIV treatment is the CD4 count, which in normal adults ranges from 500 to 1500 cells/µl. A low CD4 count is an indicator of HIV infection, and once it falls below approximately 200 cells/µl, AIDS may develop. An increase in CD4 count (eg, an increase of approximately 50, 100, 200, or more cells per µl) is also an indicator of the effectiveness of anti-HIV treatment. The CD4 count should specifically increase to a level above about 200 cells/µl, or above about 350 cells/µl. The extent of HIV infection can be diagnosed using viral load or CD4 count, or both. Another parameter to measure the effectiveness of HIV treatment is the maintenance of virological suppression (HIV-1 RNA <50 copies/mL) in an HIV-infected subject when treated in accordance with the present invention.

The term "treatment of HIV infection" and similar terms refer to treatment that reduces viral load, or increases CD4 count, or both, as described above. In one embodiment, the term "treatment of HIV infection" and similar terms refer to treatment that reduces viral load, or increases CD4 count, or maintains virological suppression in a subject infected with HIV, or two or more of these three, as described above. The term "prevention of HIV infection" and similar terms refer to a decrease in the relative number of new infections in a population exposed to a source of HIV infection (e.g., HIV-containing substances, or HIV-infected subjects). Effective prevention can be measured, for example, by measuring whether the relative number of newly infected individuals is reduced in a mixed population of HIV-infected and uninfected individuals when comparing uninfected individuals treated with the pharmaceutical composition of the invention to untreated uninfected individuals. This reduction can be measured by statistical analysis of the number of infected and uninfected individuals in a given population over time.

In a second aspect of the present invention, there is provided a method for treating or preventing HIV infection in a subject, the method comprising administering to the subject a therapeutically effective amount of an enzyme in the form of micron or nanoparticles in a suspension. Rilpivirine or a pharmaceutically acceptable salt thereof, which is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof Acceptable salts are administered intermittently at intervals of about three to seven months.

It will be understood that all embodiments described herein related to the first aspect (eg, embodiments related to rilpivirine in the present invention and the use of rilpivirine in the present invention) are equally applicable to the present invention. This second aspect is also disclosed herein in connection with this second aspect of the invention.

In a third aspect, there is provided a use of rilpivirine or a pharmaceutically acceptable salt thereof for manufacturing a medicament for treating or preventing HIV infection in a subject, wherein the rilpivirine or a pharmaceutically acceptable salt thereof The salt is in the form of micron or nanoparticles in a suspension, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 0.1 mL/min to about 15 mL/min of the suspension. The flow rate of the liquid is administered to the subject, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about seven months.

It will be understood that all embodiments described herein related to the first aspect (eg, embodiments related to rilpivirine in the present invention and the use of rilpivirine in the present invention) are equally applicable to the present invention. This third aspect is also disclosed herein in connection with this third aspect of the invention.

In one embodiment, the methods or uses described herein are used in combination with one or more other active agents, in particular one or more other antiretroviral agents, in particular one or more other antiretroviral agents of another class. , such as, for example, integrase strand transfer inhibitor (Integrase Strand Transfer Inhibitor, INSTI) antiretroviral drugs, such as, for example, cabotegravir (cabotegravir). In one embodiment, the one or more other antiretroviral agents (e.g., cabotegravir) are administered as a subcutaneous injection, particularly as an injectable micro or nano suspension, for about three to about seven months. Time interval is given. In one embodiment, the one or more other antiretroviral agents (e.g., cabotegravir) are administered at the same intermittent time intervals as rilpivirine or a pharmaceutically acceptable salt thereof as described herein. For example, rilpivirine or its pharmaceutically acceptable salt and other antiretroviral agents are administered for about three months, or about four months, or about five months, or about six months, or about seven weeks. Administered intermittently at monthly intervals. In one embodiment, rilpivirine, or a pharmaceutically acceptable salt thereof, and one or more other antiretroviral agents (eg, cabotegravir) are administered simultaneously or sequentially by subcutaneous injection. In one embodiment, rilpivirine, or a pharmaceutically acceptable salt thereof, and one or more other antiretroviral agents (eg, cabotegravir) are administered simultaneously by subcutaneous injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof and one or more other antiretroviral agents (eg, cabotegravir) are administered sequentially by subcutaneous injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered first, followed by cabotegravir injection. In one embodiment, cabotegravir injection is administered first, followed by rilpivirine or a pharmaceutically acceptable salt thereof.

In one embodiment, one or more other antiretroviral agents, in particular one or more other antiretroviral agents of another class are integrase inhibitors. Subcutaneous medical injection device containing rilpivirine or a pharmaceutically acceptable salt thereof according to the present invention

Generally, the rilpivirine or its pharmaceutically acceptable salt as used in the present invention is provided in a subcutaneous medical injection device. The subcutaneous medical injection device has a form that allows the rilpivirine or its pharmaceutically acceptable salt as used in the present invention to be dispensed from the subcutaneous medical injection device when needed.

In one embodiment, a subcutaneous medical injection device includes a container and a discharge nozzle connected to an actuator, the discharge nozzle being sized to deliver rilpivirine or a pharmaceutically acceptable salt subcutaneously to a patient. The container can contain rilpivirine or a pharmaceutically acceptable salt thereof as used in the present invention, and the actuator is configured to drive rilpivirine or a pharmaceutically acceptable salt thereof from the container and out of the discharge nozzle at a flow rate of about 0.1 mL/min to about 15 mL/min of suspension. In some examples, the container can be removably coupled to the housing of the subcutaneous injection device.

According to a fourth aspect of the present invention, the container contains a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to be present in the patient. Maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt for at least three months.

According to an eighth aspect of the present invention, the container contains a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months.

According to an embodiment of the present invention, a subcutaneous medical injection device may be a wearable device, an extracorporeal device, or a handheld device. A wearable device (also referred to as a "wearable device" and a "patch pump") includes a container and an actuator, both of which are adhered to the injection site. This article describes an example of a wearable device with reference to FIGS. 3A and 3B. Extracorporeal devices include actuators that are not adhered to the injection site, such as infusion pumps and injection pumps. This article describes an example of an extracorporeal device with reference to FIGS. 5 and 6. A handheld device includes an injection device that must be held against the injection site by hand, such as a syringe and an auto-injector. An example of a handheld device is described with reference to FIGS. 1 and 2.

Therefore, there are many different types of subcutaneous medical injection devices that form embodiments of the present invention, including: syringes, auto-injectors, syringe pumps, infusion pumps, and patch pumps.

Such subcutaneous medical injection devices may have rilpivirine or its pharmaceutically acceptable salt in the form of micro- or nanoparticles in suspension in the container of the subcutaneous medical injection device. Alternatively, such subcutaneous medical injection devices may be combined with a drug supply device so that the drug supply device provides the drug to the subcutaneous medical injection device via an introducer. For example, a vial may be used to provide rilpivirine or its pharmaceutically acceptable salt to the container of an automatic syringe via a discharge nozzle. In any case, the subcutaneous medical injection device contains rilpivirine or its pharmaceutically acceptable salt in its container before delivering the drug to the patient.

In one embodiment, the discharge nozzle may include an injection needle or catheter. The discharge nozzle may be 23-gauge to 25-gauge (inner diameter approximately 0.330 mm to 0.250 mm), such as 23-gauge, 24-gauge, or 25-gauge. The discharge nozzle may have a length of about 12.7 mm to about 19.1 mm long.

In one embodiment, the discharge nozzle may include a syringe needle or catheter. The discharge nozzle may have a specification of 21-gauge to 25-gauge (inner diameter of about 0.514 mm to about 0.250 mm), such as 21-gauge, 22-gauge, 23-gauge, 24-gauge, or 25-gauge. The discharge nozzle may have a length of about 12.7 mm to about 19.1 mm long.

In one embodiment, the subcutaneous medical injection device is a syringe or syringe pump, which may include a discharge nozzle, which may include an injection needle, a catheter, or an infusion set. The discharge nozzle may be 23-gauge to 25-gauge (inner diameter approximately 0.330 mm to 0.250 mm), such as 23-gauge, 24-gauge, or 25-gauge. The discharge nozzle may have a length of about 12.7 mm to about 19.1 mm long.

In one embodiment, the subcutaneous drug injection device is a syringe or a syringe pump, which may include a discharge nozzle, which may include a syringe needle, a catheter, or an infusion set. The discharge nozzle may have a specification of 21 to 25 (inner diameter of about 0.514 mm to about 0.250 mm), such as 21, 22, 23, 24, or 25. The discharge nozzle may have a length of about 12.7 mm to about 19.1 mm.

In one embodiment, a subcutaneous medical injection device may have a housing that houses a container and an actuator.

In one embodiment, a subcutaneous medical injection device may include a container in the form of one of a vial, a cartridge, a syringe body, and an expandable member. The container may be removably coupled to the housing of the hypodermic device, or may be fixedly attached to or integral with the housing.

In one embodiment, the container of the subcutaneous medical injection device may contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. In one embodiment, the container of the subcutaneous medical injection device may contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, 45 mL, 50 mL, 55 mL, or 60 mL.

The release of rilpivirine or its pharmaceutically acceptable salt from the container can be initiated by the user. To achieve this, one embodiment of the subcutaneous medical injection device may have a trigger for initiating the release of rilpivirine or its pharmaceutically acceptable salt from the container by the actuator. This allows controlled administration of rilpivirine or its pharmaceutically acceptable salt to the patient.

One embodiment of a subcutaneous injection device may include a metering mechanism that measures the dose released from the container by the driver. In this manner, the subcutaneous medical injection device can provide known dose sizes. Dose selector available. The dose selector enables the user to select a dose of the drug, which dose is measured by a metering mechanism. This allows control over the size of the dose.

In one embodiment, a subcutaneous medical injection device may have at least one environmental sensor configured to sense information related to the environment in which the device is located, such as the temperature of the environment.

In one embodiment, the subcutaneous medical injection device may include at least one drug sensor configured to sense information related to rilpivirine or a pharmaceutically acceptable salt thereof contained in the subcutaneous medical injection device. .

In one embodiment, a subcutaneous injection device may include a device indicator configured to present information regarding the status of the subcutaneous injection device and/or rilpivirine or a pharmaceutically acceptable salt thereof contained therein. .

In one embodiment, a subcutaneous medical injection device may be enclosed in a package. The package may include an environmental sensor and/or a device indicator as described herein.

In one embodiment, a subcutaneous medical injection device may include a device operation prevention mechanism that may prevent and/or stop the actuator from releasing rilpivirine or a pharmaceutically acceptable salt thereof from the container. This prevents unintentional delivery of rilpivirine or a pharmaceutically acceptable salt thereof.

In one embodiment, a subcutaneous medical injection device may include a user interface that may be configured to present information about the subcutaneous medical injection device to a user of the subcutaneous medical injection device and/or enable the user to control certain aspects of the subcutaneous medical injection device, including an overview of drug administration and dose size.

In one embodiment, a subcutaneous medical injection device may include at least one device sensor that senses information about the device. As an example, a subcutaneous medical injection device may have a sensor configured to sense the actual dose delivered by the driver.

One embodiment of the subcutaneous injection device may include a power supply to provide power to one or more components of the subcutaneous injection device when needed. The power supply may be a power source integrated with the device, and/or a mechanism for connecting the subcutaneous medical injection device to an external power source.

In a fifth aspect, a method of administering a pharmaceutical composition using a subcutaneous injection device is provided. The method includes: inserting a discharge nozzle of the subcutaneous injection device into the subcutaneous layer of a patient; causing a driver of the subcutaneous injection device to transfer a volume Rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is driven from the container of the injection device and the suspension is dispersed at about 0.1 mL/min to about 15 mL/min. The flow rate of liquid driven from the discharge nozzle is greater than 3 mL and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in the patient for at least three months. In one embodiment, this method may be repeated at intervals of at least three months.

In an embodiment of the fifth aspect of the invention, the method may include, after inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient, and causing the driver of the hypodermic injection device to discharge the volume of Rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is driven from the container of the injection device and driven out of the discharge nozzle to enable fluid to flow between the discharge nozzle and The injection device flows between the containers.

In an alternative embodiment of the fifth aspect, the method may include allowing fluid to flow between the discharge nozzle and the container of the injection device before inserting the discharge nozzle of the subcutaneous injection device into the subcutaneous layer of the patient and before causing the actuator of the subcutaneous injection device to drive the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension from the container of the injection device and out of the discharge nozzle.

In a sixth aspect, a method of preparing a subcutaneous injection device for injection is provided, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or its pharmaceutically acceptable salt in the form of micron or nanoparticles in suspension, and the volume is greater than 3 mL and sufficient to maintain therapeutic levels of rilpivirine or its pharmaceutically acceptable salt in patients At least three months.

In an embodiment of the sixth aspect, introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device includes introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof Draw into the container of the hypodermic injection device. In another embodiment of the sixth aspect, introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device includes introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof Saline is injected into the container of the hypodermic injection device. In another embodiment of the sixth aspect, introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device includes inserting a container into the hypodermic injection device, the container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof Rilpivirine or its pharmaceutically acceptable salt.

In an embodiment of the sixth aspect, a subcutaneous injection device includes a discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient. In an embodiment of the sixth aspect, the subcutaneous injection device includes a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof.

In a seventh aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and to deliver the rilpivirine or the pharmaceutically acceptable salt to the patient at a rate of about 0.1 mL/min to about 15 mL/min of the suspension is driven from the discharge nozzle; and the kit comprises a drug supply device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain therapeutic levels of the rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months. The kit may comprise an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of a subcutaneous medical injection device, or the container may be pre-filled with the volume. In one aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and to deliver the rilpivirine or the pharmaceutically acceptable salt to the patient at a rate of about 0.1 mL/min to about 15 mL/min of the suspension is driven out of the discharge nozzle; and the kit comprises a drug supply device, the drug supply device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months, and wherein the kit comprises an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the subcutaneous medical injection device.

In a ninth aspect, a method for administering a drug using a subcutaneous injection device is provided, the method comprising: inserting a discharge nozzle of the subcutaneous injection device into the subcutaneous layer of a patient; and causing an actuator of the subcutaneous injection device to drive a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in a suspension from a container of the injection device and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min, wherein the micro- or nanoparticles have a D _v 90 of about 4 μm to about 6 μm, a D _v 50 of about 1.5 μm to about 2 μm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months.

In a tenth aspect, a method of preparing a subcutaneous injection device for injection is provided, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, about 1.5 µm to about 2 µm D _v 50, and a D _v 10 of about 300 nm to about 500 nm, and the volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months.

In an eleventh aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 μm to about 6 μm, a D _v 50 of about 1.5 μm to about 2 μm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain a therapeutic level of the rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or a pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or a pharmaceutically acceptable salt from the container and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min; and a drug delivery device containing a volume of the rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D v of about 300 nm to about 500 nm D _v 10, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of the rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months. The kit may comprise an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of a subcutaneous medical injection device, or the container may be pre-filled with the volume. In one aspect, a kit is provided, comprising: a subcutaneous medical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 μm to about 6 μm, a D _v 50 of about 1.5 μm to about 2 μm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain a therapeutic level of the rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or a pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or a pharmaceutically acceptable salt from the container and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min; and a drug delivery device containing a volume of the rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D v of about 300 nm to about 500 nm in D _v 10, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of the rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months, and wherein the kit comprises an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the subcutaneous medical injection device.

It will be understood that all embodiments described herein related to the fourth and eighth aspects (for example, embodiments related to subcutaneous medical injection devices) are equally applicable to the fifth, sixth, seventh, ninth, and ninth aspects of the present invention. The tenth and eleventh aspects are also disclosed herein in connection with the fifth, sixth, seventh, ninth, tenth and eleventh aspects of the present invention.

Similarly, it will be understood that all embodiments described herein in connection with the fifth aspect (e.g., a method of administering a pharmaceutical composition using a subcutaneous injection device) are equally applicable to the ninth aspect of the present invention, that is, they are also disclosed herein in connection with the ninth aspect of the present invention.

Similarly, it will be understood that all embodiments described herein in relation to the sixth aspect (e.g., a method for preparing a subcutaneous injection device for injection) are equally applicable to the tenth aspect of the present invention, that is, they are also disclosed herein in relation to the tenth aspect of the present invention.

The following specific types of subcutaneous medical injection devices, methods of administering drugs using the subcutaneous medical injection devices, methods of preparing the subcutaneous injection devices for injection, and kits including a drug delivery device and the subcutaneous medical injection devices will now be described. As will be understood by one of ordinary skill in the art, when the following description refers to a "drug", the "drug" is: a) a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in a patient for at least three months; or b) a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or its pharmaceutically acceptable salt in the patient for at least three months. Syringe

Figure 1 shows a subcutaneous medical injection device in the form of a syringe 100. Syringe 100 is of a conventional type and includes a container in the form of a syringe body 110 ending at one end with a discharge nozzle in the form of an injection needle 112 . The syringe body 110 contains the medicament according to the invention. Syringe 100 further includes a driver in the form of plunger 114 . A plunger may be used to manually actuate the contents of syringe 100 from syringe body 110 and out of injection needle 112 at a flow rate of about 0.1 mL/min to about 15 mL/min. Alternatively, the contents of the syringe may be automatically discharged at a flow rate of about 0.1 mL/min to about 15 mL/min, as will be described with reference to automatic injectors and syringe pumps set forth below.

Alternatively, fluid flow between the discharge nozzle in the form of the injection needle 112 and the container in the form of the syringe body 110 may be achieved by removing the cap of the injection needle 112 . After removing the cap from the injection needle, the injection needle can be inserted into the patient's subcutaneous layer and the plunger 114 can be used to drive the contents of the syringe from the syringe body 110 and out of the injection needle 112 .

As will be understood by one of ordinary skill in the art, a user may introduce a volume of medication into a syringe body 110 by inserting an injection needle 112 into a medication delivery device containing a medication according to the present invention and pulling a plunger 114 to draw the medication from the medication delivery device, through the injection needle 112 and into the syringe body 110. Automatic syringe

Figure 2 shows an example of a subcutaneous medical injection device in the form of an auto-injector 200, with a housing 230 containing the syringe. The syringe is of a known type and includes a container in the form of a syringe body 210 ending with an injection needle 212 at one end. Injection needle 212 is sized to deliver the drug (ie, rilpivirine or a pharmaceutically acceptable salt thereof according to the present invention) subcutaneously from the container to the patient. The syringe body 210 contains the medicament according to the invention. The conventional plunger normally used to manually discharge the contents of the syringe has been removed and replaced with an actuator 220 configured to drive the contents of the syringe body 210 from about 0.1 mL/min to about 15 mL /min flow rate is driven from the injection needle 212. The driver includes a drive element 214 (as will be described below) that terminates at a plug 222 . This drive element 214 confines the medicament to be administered within the syringe body 210.

As shown, the housing includes a return spring 242 that biases the syringe from an extended position where the injection needle 212 extends from the aperture in the housing 230 to where the injection needle 212 is contained within the housing 230 retracted position. A return spring 242 acts on the syringe via a sleeve 241 .

A trigger 251 is provided and, when operated, serves to separate the drive sleeve 226 from the housing 230, causing it to move relative to the housing 230 under the influence of the drive spring 227. The drive from the drive spring 227 is transmitted to the syringe 210 via the drive sleeve 226 and the drive element 214 to advance the syringe from its retracted position to its extended position and discharge its contents through the needle 212, thereby acting as an actuator. The actuation accomplishes this task by acting directly on the medication and the syringe. Initially the hydrostatic force of the fluid of the drug and to a lesser extent the static friction between the stopper 222 and the syringe body 210 ensure that they are pushed together until the return spring 242 reaches its bottom point or the syringe body 210 encounters some other obstacle that impedes its movement.

Since the static friction between the driving element 214 and the syringe body 210 and the hydrostatic force acting through the drug to be administered are not sufficient to resist the full driving force generated by the driving spring 227, at this time, the driving element 214 begins to move in the syringe. The body 210 moves within, and the drug begins to be discharged through the injection needle 212 at a flow rate of about 0.1 mL/min to about 15 mL/min. However, the dynamic friction between the drive element 214 and the syringe body 210 and the hydrostatic forces acting through the drug to be administered are sufficient to maintain the return spring 214 in its compressed state, so the hypodermic needle 212 remains extended.

When the drive element 214 reaches the end of its travel in the syringe body 210, the drive element 214 is unlatched from the drive sleeve 226 so that the force generated by the drive spring 227 is no longer transmitted to the syringe 210.

At this point, the only force acting on the syringe 210 will be the return force from the return spring 242. Therefore, the syringe 210 is now returned to its retracted position and the injection cycle is completed. All of this only occurs after the cap is removed from the end of the housing 230 and the needle cover is removed from the syringe 210. Removing the cap allows fluid to flow between the discharge nozzle in the form of an injection needle and the container in the form of the syringe body 210.

As will be appreciated by one of ordinary skill in the art, a user may introduce a volume of medication into the syringe body by inserting the syringe 210 into a subcutaneous injection device, the syringe 210 containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof according to the present invention.

Although the foregoing description relates to one example of an autoinjector, the present invention is not limited to this one autoinjector. Those skilled in the art will appreciate that various other modifications of the autoinjector may be used with the present invention. For example, the autoinjector may be pneumatic, electric, or powered by a torsion spring. Patch Pump

Figure 3A shows an example of a subcutaneous medical injection device in the form of a patch pump 300.

The patch pump 300 includes a housing 330 having a bottom side 332 and an injection button 351 having a return spring 342 .

Patch pump 300 also includes a container in the form of an expandable member 310, such as a balloon or bladder. Expandable member 310 is formed from an elastic material such that it is configured to retain a volume of drug under pressure and provide elasticity to expel the drug from expandable member 310 . Patch pump 300 also includes a discharge nozzle in the form of an injection needle 312 which further includes a side hole 313 . Patch pump 300 further includes internal tubing 314 configured to provide fluid communication between expandable member 310 and injection needle 312, as will be described below.

In use, the patch pump 300 is placed on the patient so that the bottom side 332 contacts the patient's skin. The bottom side 332 may include an adhesive that is configured to releasably attach the patch pump 300 to the patient's skin. Then, the injection button 351 is depressed to insert the needle 312 into the patient's subcutaneous layer to the injection site. Depressing the injection button 351 also aligns the internal tubing 314 with the side hole 313, so that the expandable member 310 is fluidly connected to the injection needle 312. In this way, the user enables fluid to flow between the discharge nozzle in the form of the injection needle 312 and the container in the form of the expandable member 310. The user can enable the fluid to flow after inserting the injection needle 312 into the subcutaneous layer of the patient, or before inserting the injection needle into the subcutaneous layer of the patient. A stop (not shown) may be provided to limit the injection depth reached by the injection needle 312. Due to the pressure from the expandable member 310, the drug is driven out of the injection needle 312. In this way, the elastic material of the expandable member 310 provides a driver that is configured to drive the drug from the expandable member 310 and out of the injection needle 312 at a flow rate of about 0.1 mL/min to about 15 mL/min. Once the expandable member 310 has driven out all the drug, the injection button 351 can be released and the return spring 342 will push the injection button to the final post-injection position.

As one of ordinary skill in the art will understand, a user may introduce a volume of drug into the expandable member 310 by injecting the volume of rilpivirine or a pharmaceutically acceptable salt thereof subcutaneously In the container of the injection device.

Although the foregoing description relates to an example of a patch pump, the present invention is not limited to this patch pump. Those of ordinary skill in the art will appreciate that various other modifications to the patch pump may be used with the present invention. For example, the container may contain a syringe or vial.

Figure 3B shows another example of a patch pump 400. Patch pump 400 includes a housing 430 having a bottom side 432 and an injection button 451.

Patch pump 400 also includes a container in the form of a vial or cartridge 410, a discharge nozzle in the form of an injection needle 412, and a driver in the form of a drive spring 427, and stopper 422. In use, patch pump 400 is placed on the patient such that bottom side 432 is in contact with the patient's skin, and injection needle 412 is inserted into the patient's subcutaneous layer into the injection site. The injection button can be pulled up so that the drive spring 427 acts on the stopper 422 to drive the stopper 422 through the vial and drive the drug from the vial or cartridge 410 through the line 413 at a rate of between about 0.1 mL/min to about 15 mL/min. The flow rate is driven from the injection needle 412.

As will be appreciated by one of ordinary skill in the art, a user may introduce a volume of drug into the syringe body by inserting a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device.

Although the foregoing description relates to one example of a patch pump, the present invention is not limited to this one patch pump. One of ordinary skill in the art will appreciate that various other modifications of the patch pump may be used with the present invention. For example, the driver may be gas or electric. Subcutaneous Infusion Set

FIG. 4 shows a subcutaneous medication injection device in the form of a subcutaneous infusion set 500. The subcutaneous infusion set 500 includes a housing 530, a discharge nozzle in the form of an injection needle 512, and tubing 513 configured to provide fluid communication between a container containing a medication and the injection needle 512. The arrow indicates the connection between the injection needle 512 and the container containing the medication. Optionally, the subcutaneous infusion set 512 includes wings 515, 516 configured to limit the injection depth reached by the injection needle 512.

The tubing 513 includes a connection feature (e.g., a Y-connector or a luer connection) configured to connect the tubing 513 to a container fluid containing a drug, and an actuator configured to drive the drug from the container and out of the injection needle 512. For example, the container and the actuator may include one or more of the following: a syringe, such as the syringe 100 described with reference to FIG. 1; a syringe pump, such as the syringe pump 600 described with reference to FIG. 5; and an infusion pump, such as the infusion pump described with reference to FIG. 6.

In use, the subcutaneous infusion set 500 is placed on the patient's skin such that the injection needle 512 is inserted into the patient's subcutaneous layer into the injection site. The user may enable fluid to flow between the injection needle 512 and the container via the tubing 513 after the injection needle 512 is inserted into the patient's subcutaneous layer, or before the injection needle 512 is inserted into the patient's subcutaneous layer. Next, a driver is used to drive the drug from the container and out of the injection needle 512 at a flow rate of about 0.1 mL/min to about 15 mL/min. For example, plunger 114 may be used to drive medication from syringe body 100 through tubing 513 and out of injection needle 512. In another example, syringe pump 600 may be used to drive medication from syringe 610 through tubing 613 and out of injection needle 512. In another example, an infusion pump 700 may be used to drive medication from reservoir 710 through infusion line 712 and out of injection needle 512 .

Although the foregoing description relates to an example of a subcutaneous infusion set, the present invention is not limited to such a subcutaneous infusion set. Those of ordinary skill in the art will appreciate that various other modifications to the subcutaneous infusion set may be used with the present invention. Injection pump

In some cases, medical patients require precise delivery of continuous medication or precise delivery of medication at set cycle intervals. Syringe pumps provide controlled drug infusion by facilitating the administration of drugs at precise rates so that drug concentrations remain within therapeutic margins without the need for frequent attention. The syringe pump can be non-pulsatile.

Figure 5 shows an example of a subcutaneous medical injection device in the form of a syringe pump 600. Syringe pump 600 includes a container in the form of a syringe 610 configured to hold a volume of medication, and a syringe holder 630 configured to hold the syringe. Injector 610 is in fluid communication with line 613 and the discharge nozzle (indicated by the arrow in Figure 5). Syringe pump 600 further includes a driver in the form of plunger 614, and a motor-driven actuator 616 that pushes plunger 614 into syringe 610 to drive medication from syringe 610. Syringe pump 600 further includes a housing 696 that contains a motor for driving actuator 616 and a processor and memory for controlling the motor. Housing 696 may also include user interfaces 680, 681 that may be used to set usage parameters of syringe pump 600. Syringe pump 600 can be powered by a battery pack or mains power.

During use, syringe 610 is placed into syringe holder 630. The syringe pump may include a sensor configured to sense whether the syringe is correctly placed within syringe holder 630 and prevent use of the syringe unless the syringe is correctly placed within syringe holder 630. As will be understood by those of ordinary skill in the art, the user can insert the tubing 613 into a medication delivery device containing a medication according to the present invention and pull the plunger 614 to withdraw the medication from the medication delivery device. A volume of medication is introduced into syringe body 610 through tubing 613 and into syringe body 610 .

Then, the user interface 680, 681 can be used to operate the syringe pump 600. For example, the user interface can be used to select the speed and duration at which the motor should operate. In another example, the user interface can be used to indicate what kind of drug is in the syringe, and then the syringe pump 600 will operate according to the predetermined settings.

Next, the motor drives the actuator 616, which pushes the plunger 614 into the syringe 610 to drive the drug from the syringe 610 and through the tubing 613. The tubing 613 is connected to a discharge nozzle, which is configured to deliver the drug to the patient subcutaneously at a flow rate of 0.1 mL/min to about 15 mL/min. For example, the tubing 613 can be connected to a subcutaneous infusion set, such as the subcutaneous infusion set described with reference to FIG.

The syringe pump 600 may also include safety features. For example, the syringe pump 600 may be configured to provide visual or audible alarms in the following events: the pressure in the tubing 613 is too high or too low, the syringe pump 600 battery is empty or nearly empty, the syringe 610 is nearly empty, and/or the syringe holder 630 detects that the syringe 610 is not installed correctly.

Although the foregoing description relates to an example of a syringe pump, the invention is not limited to such a syringe pump. Those of ordinary skill in the art will appreciate that various other modifications to the syringe pump may be used with the present invention. For example, the processor may be preprogrammed so that the syringe pump does not need to include a user interface. infusion pump

Similar to syringe pumps, infusion pumps provide controlled infusion of medication by facilitating administration of medication at a precise rate so that drug concentrations remain within therapeutic limits without the need for frequent attention.

Figure 6 shows a subcutaneous medical injection device in the form of an infusion pump 700. Infusion pump 700 includes a container in the form of a reservoir 710 for containing medication to be delivered, and a driver including a pump 716 adapted to dispense the medication contained in the reservoir such that the medication can be delivered. Delivered to patient. Medication is delivered from the reservoir upon actuation of pump 716 via infusion line 712, which may take the form of a cannula or subcutaneous infusion set, such as the one described with reference to FIG. 4 . Pump 716 may take the form of an elastomeric pump, a peristaltic pump, or an osmotic pump. Pump 716 is configured to drive drug from reservoir 716 and out of the discharge nozzle at a flow rate of about 0.1 mL/min to about 15 mL/min.

Actuation of the pump 716 is controlled by a processor 796 electrically coupled to the pump. The processor can be programmed by a user via a user interface 780 so that the infusion pump 700 can provide medication to a patient in a controlled manner. The user can input parameters such as infusion duration and delivery rate according to the present invention. The programmed parameters for controlling the pump 716 are stored in and retrieved from a memory 797 that communicates with the processor 796. The user interface 780 can take the form of a touch screen or a keypad.

Power supply 795 provides power to infusion pump 700 and may take the form of a power supply integrated with infusion pump 700 and/or a mechanism for connecting infusion pump 700 to an external power source. Infusion pumps can take various forms, including stationary bedside devices, as well as ambulatory infusion pumps designed to be portable or wearable. The integrated power supply 795 is particularly beneficial for portable infusion pumps.

As will be appreciated by one of ordinary skill in the art, introducing a drug according to the present invention into the infusion pump 700 may include inserting a reservoir 710 containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a subcutaneous injection device.

Although the foregoing description relates to one example of an infusion pump, the present invention is not limited to such an infusion pump. One of ordinary skill in the art will appreciate that various other modifications to the infusion pump described may be used with the present invention. For example, the processor may be pre-programmed so that the infusion pump does not have to include a user interface. General Definitions

The term "comprising" encompasses "including" as well as "consisting", for example, a composition "comprising" X may consist of X alone, or may include something additional, such as X + Y. The term "comprising" as used herein also encompasses "consisting essentially of", for example, a composition "comprising" X may consist of X and any other components that do not materially affect the basic characteristics of the composition.

The term "about" in relation to a value Y is optional and means, for example, Y ± 10%.

When a time interval is expressed in a specified number of months, it runs from a given numbered date in a given month to the same numbered date in the month following the specified number of months. When the same numbered date does not exist in the month after the specified number of months, the time interval will be extended to the next month for the same number of days, which is the number of days that should be run if the same numbered date exists in the month after the specified number of months. number of days.

When a time interval is expressed as a number of years, it runs from a given date in a given year to the same numbered date in the year after the specified number of years. When the same number of days does not exist in the year after the specified number of years, the interval runs the same number of days as it would have if the same numbered date existed in the month after the specified number of years. In other words, if a time interval begins on February 29 of a given year, but ends in a year that does not have a February 29, then the time period ends on March 1 of that year instead.

The term "about" in connection with these definitions means that the time interval may end on a date that is ± 10% of the time interval.

In one embodiment, a time interval may start up to 7 days before or after the start of the time interval and end up to 7 days before or after the end of the time interval.

All references cited herein are incorporated by reference in their entirety. The invention will now be described with reference to the following numbered items. For the avoidance of doubt, these numbered terms do not limit the scope of the invention. Modifications may be made while remaining within the scope and spirit of the invention. 1. A rilpivirine or a pharmaceutically acceptable salt thereof for treating or preventing HIV infection in a subject, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in the form of microns or nanometers in suspension in the form of particles, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min, and wherein the rilpivir Lin or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about seven months. 2. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein the time interval is about six months. 3. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1 or 2, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 300 mg to Dosage calculations for rilpivirine in the range of approximately 1200 mg/month. 4. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 350 mg to Dosage calculations for rilpivirine in the range of approximately 900 mg/month. 5. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 350 mg to Dosage calculations for rilpivirine in the range of approximately 550 mg/month. 6. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 400 mg to Dosage calculations for rilpivirine in the range of approximately 500 mg/month. 7. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on about 450 mg/month Dosage calculation of rilpivirine. 8. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 4, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on about 500 Dosage calculations for rilpivirine in the range of mg to approximately 700 mg/month. 9. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 8, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 550 mg to about 650 mg/ Rilpivirine dose calculation within the range of months. 10. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 9, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on about 600 mg/month of rilpivir Lin's dose calculation. 11. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof includes about 1350 mg in each administration, and The time interval is approximately three months. 12. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof includes about 1800 mg in each administration, and The time interval is approximately four months. 13. The rilpivirine or a pharmaceutically acceptable salt thereof of embodiment 1, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof includes about 2250 mg in each administration, and wherein This time interval is approximately five months. 14. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1 or 2, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof includes approximately 2700 mg, and the interval is approximately six months. 15. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof includes about 3150 mg in each administration, and The time interval is approximately seven months. 16. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a rate of about 0.25 mL/min to The suspension was administered at a flow rate of approximately 9 mL/min. 17. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 0.3 mL/min. The suspension was administered at a flow rate of approximately 6 mL/min. 18. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 0.5 mL/min. The suspension was administered at a flow rate of approximately 3 mL/min. 19. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 0.5 mL/min The suspension was administered at a flow rate of approximately 2 mL/min. 20. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 16, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 9 mL The flow rate of the suspension is /min. 21. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 17, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 6 mL The flow rate is /min. 22. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 18, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 3 mL The flow rate of the suspension is /min. 23. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 19, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 2 mL The flow rate of the suspension is /min. 24. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 19, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 1 mL The flow rate of the suspension is /min. 25. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of embodiments 1 to 19, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at about 0.5 mL The flow rate of the suspension is /min. 26. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the volume of the suspension administered is from about 3 mL to about 150 mL. 27 Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the volume of the suspension administered is from about 6 mL to about 12 mL. 28. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the volume of the suspension administered is from about 8 mL to about 10 mL. 29. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the volume of the suspension administered is about 9 mL. 30. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 350 mg to about 550 mg/ Calculation of dosages of rilpivirine within the range of 3 months, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.3 mL/min to about 6 mL/min. is administered, and the volume of the suspension administered is about 6 mL to 12 mL. 31. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 1, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dosage of from about 350 mg to about 550 mg/ Calculation of dosages of rilpivirine within the range of 3 months, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.5 mL/min to about 3 mL/min. is administered, and the volume of the suspension administered is about 8 mL to 10 mL. 32. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the micron or nanoparticles have a surface modifier adsorbed to their surface. 33. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 32, wherein the surface modifier is poloxamer. 34. Rilpivirine or a pharmaceutically acceptable salt thereof as used in embodiment 33, wherein the poloxamer is bound to poloxamer 338. 35. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 36. Rilpivirine or a pharmaceutically acceptable salt thereof as used in embodiment 35, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles The particles have a Dv90 of about 500 nm to about 1,600 nm. 37. Rilpivirine or a pharmaceutically acceptable salt thereof as used in embodiment 35 or 36, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm. Nanoparticles have a Dv50 of about 200 nm to about 500 nm. 38. Rilpivirine or a pharmaceutically acceptable salt thereof as used in embodiment 35, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 39. Rilpivirine or a pharmaceutically acceptable salt thereof as used in embodiment 35 or 38, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have Dv50 from about 1.5 µm to about 2 µm. 40. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the suspension comprises a pharmaceutically acceptable aqueous carrier, the rilpivirine or a pharmaceutically acceptable salt thereof of salt suspended in it. 41. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the treatment or prevention of HIV infection is the treatment of HIV infection. 42. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the HIV infection is HIV type 1 (HIV-1) infection. 43. Rilpivirine or a pharmaceutically acceptable salt thereof for use in any one of the preceding embodiments, wherein the subject is a human. 44. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is rilpivirine. 45. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered subcutaneously by using a subcutaneous medical injection device. Administered by injection. 46. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any one of the preceding embodiments, wherein the flow rate is constant throughout the administration. 47. Rilpivirine or a pharmaceutically acceptable salt thereof as used in any of the preceding embodiments, wherein the suspension is co-administered with an HIV inhibitor of another class to the NNRTI rilpivirine. 48. Rilpivirine or a pharmaceutically acceptable salt thereof as used in Example 47, wherein the HIV inhibitor to which the NNRTI rilpivirine is another class is an integrase inhibitor. 49. A method of treating or preventing HIV infection in a subject, the method comprising administering rilpivirine or a pharmaceutically acceptable salt thereof to the subject, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in the form of In the form of micron or nanoparticles in a suspension, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. is administered, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about seven months. 50. The method of embodiment 49, wherein the time interval is about six months. 51. The method of embodiment 49 or 50, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose of rilpivirine in the range of about 300 mg to about 1200 mg/month. Dose Calculation. 52. The method of any one of embodiments 49 to 51, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 350 mg to about 900 mg/month. Piverine dose calculation. 53. The method of any one of embodiments 49 to 52, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 350 mg to about 550 mg/month. Piverine dose calculation. 54. The method of any one of embodiments 49 to 53, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 400 mg to about 500 mg/month. Piverine dose calculation. 55. The method of any one of embodiments 49 to 54, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of about 450 mg/month of rilpivirine. 56. The method of any one of embodiments 49 to 52, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 500 mg to about 700 mg/month. Piverine dose calculation. 57. The method of embodiment 56, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 550 mg to about 650 mg/month. . 58. The method of embodiment 57, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of about 600 mg/month of rilpivirine. 59. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 1350 mg in each administration, and wherein the time interval is about three months. 60. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 1800 mg in each administration, and wherein the time interval is about four months. 61. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 2250 mg in each administration, and wherein the time interval is about five months. 62. The method of embodiment 49 or embodiment 50, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 2700 mg in each administration, and wherein the time interval is about six moon. 63. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 3150 mg in each administration, and wherein the time interval is about seven months. 64. The method of any one of embodiments 49 to 63, wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.25 mL/min to about 9 mL/min. Flow rate dosing. 65. The method of any one of embodiments 49 to 64, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.3 mL/min to about 6 mL/min. The flow rate is given. 66. The method of any one of embodiments 49 to 65, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.5 mL/min to about 3 mL/min. The flow rate is given. 67. The method of any one of embodiments 49 to 66, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.5 mL/min to about 2 mL/min. The flow rate is given. 68. The method of any one of embodiments 49 to 64, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 9 mL/min. 69. The method of any one of embodiments 49 to 65, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of about 6 mL/min. 70. The method of any one of embodiments 49 to 66, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 3 mL/min. 71. The method of any one of embodiments 49 to 67, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 2 mL/min. 72. The method of any one of embodiments 49 to 67, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 1 mL/min. 73. The method of any one of embodiments 49 to 67, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.5 mL/min. 74. The method of any one of embodiments 49 to 73, wherein the volume of the suspension administered is from about 3 mL to about 150 mL. 75. The method of any one of embodiments 49 to 74, wherein the volume of the suspension administered is from about 6 mL to about 12 mL. 76. The method of any one of embodiments 49 to 75, wherein the volume of the suspension administered is from about 8 mL to about 10 mL. 77. The method of any one of embodiments 49 to 76, wherein the volume of the suspension administered is about 9 mL. 78. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month. , wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.3 mL/min to about 6 mL/min, and wherein the administered suspension The volume is approximately 6 mL to 12 mL. 79. The method of embodiment 49, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month. , wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.5 mL/min to about 3 mL/min, and wherein the administered suspension The volume is approximately 8 mL to 10 mL. 80. The method of any one of embodiments 49 to 79, wherein the micron or nanoparticles have a surface modifier adsorbed to their surface. 81. The method of embodiment 80, wherein the surface modifying agent is moxamer. 82. The method of embodiment 81, wherein the poloxamer is moored to poloxamer 338. 83. The method of any one of embodiments 49 to 82, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 84. The method of embodiment 83, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 85. The method of embodiment 83 or 84, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. Dv50. 86. The method of embodiment 83, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 87. The method of any one of embodiments 83 to 84 and 86, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv10 of about 1.5 µm to about 2 Dv50 in µm. 88. The method of any one of embodiments 49 to 87, wherein the suspension comprises a pharmaceutically acceptable aqueous carrier in which the rilpivirine or a pharmaceutically acceptable salt thereof is suspended. 89. The method of any one of embodiments 49 to 88, wherein the treatment or prevention of HIV infection is treatment of HIV infection. 90. The method of any one of embodiments 49 to 89, wherein the HIV infection is HIV type 1 (HIV-1) infection. 91. The method of any one of embodiments 49 to 90, wherein the subject is human. 92. The method of any one of embodiments 49 to 91, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is rilpivirine. 93. The method of any one of embodiments 49 to 92, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection using a subcutaneous medical injection device. 94. The method of any one of embodiments 49 to 93, wherein the flow rate is constant throughout the administration process. 95. The method of any one of embodiments 49 to 94, wherein the suspension is co-administered with an HIV inhibitor of another class to the NNRTI rilpivirine. 96. The method of embodiment 95, wherein the HIV inhibitor to which the NNRTI rilpivirine is another class is an integrase inhibitor. 97. The use of rilpivirine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating or preventing HIV infection in a subject, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in a suspension in the form of micron or nanoparticles, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min, and wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered intermittently at intervals of about three months to about seven months. 98. The use of embodiment 97, wherein the time interval is about six months. 99. The use of embodiment 97 or 98, wherein each administration of the rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose of rilpivirine in the range of about 300 mg to about 1200 mg/month. Dose Calculation. 100. The use of any one of embodiments 97 to 99, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 350 mg to about 900 mg/month. Piverine dose calculation. 101. The use of any one of embodiments 97 to 100, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 350 mg to about 550 mg/month. Piverine dose calculation. 102. The use of any one of embodiments 97 to 101, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 400 mg to about 500 mg/month. Piverine dose calculation. 103. The use of any one of embodiments 97 to 102, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of about 450 mg/month of rilpivirine. 104. The use of any one of embodiments 97 to 100, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is based on a dose in the range of about 500 mg to about 700 mg/month. Piverine dose calculation. 105. The use of 104, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 550 mg to about 650 mg/month. 106. The use of embodiment 105, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of about 600 mg/month of rilpivirine. 107. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 1350 mg in each administration, and wherein the time interval is about three months. 108. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 1800 mg in each administration, and wherein the time interval is about four months. 109. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 2250 mg in each administration, and wherein the time interval is about five months. 110. The use of embodiment 97 or embodiment 98, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 2700 mg in each administration, and wherein the time interval is about six moon. 111. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof includes about 3150 mg in each administration, and wherein the time interval is about seven months. 112. The use of any one of embodiments 97 to 111, wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.25 mL/min to about 9 mL/min. Flow rate dosing. 113. The use of any one of embodiments 97 to 112, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.3 mL/min to about 6 mL/min. The flow rate is given. 114. The use of any one of embodiments 97 to 113, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.5 mL/min to about 3 mL/min. The flow rate is given. 115. The use of any one of embodiments 97 to 114, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection of the suspension at about 0.5 mL/min to about 2 mL/min. The flow rate is given. 116 The use of any one of embodiments 97 to 112, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 9 mL/min. 117. The use of any one of embodiments 97 to 113, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of about 6 mL/min. 118. The use of any one of embodiments 97 to 114, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 3 mL/min. 119. The use of any one of embodiments 97 to 115, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 2 mL/min. 120. The use of any one of embodiments 97 to 115, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 1 mL/min. 121. The use of any one of embodiments 97 to 115, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.5 mL/min. 122. The use of any one of embodiments 97 to 121, wherein the volume of the suspension administered is from about 3 mL to about 150 mL. 123. The use of any one of embodiments 97 to 122, wherein the volume of the suspension administered is from about 6 mL to about 12 mL. 124. The use of any one of embodiments 97 to 123, wherein the volume of the suspension administered is from about 8 mL to about 10 mL. 125. The use of any one of embodiments 97 to 124, wherein the volume of the suspension administered is about 9 mL. 126. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month. , wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.3 mL/min to about 6 mL/min, and wherein the administered suspension The volume is approximately 6 mL to 12 mL. 127. The use of embodiment 97, wherein each administration of rilpivirine or a pharmaceutically acceptable salt thereof is calculated based on a dose of rilpivirine in the range of about 350 mg to about 550 mg/month. , wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection at a flow rate of the suspension of about 0.5 mL/min to about 3 mL/min, and wherein the administered suspension The volume is approximately 8 mL to 10 mL. 128. The use of any one of embodiments 97 to 127, wherein the micron or nanoparticles have a surface modifier adsorbed to their surface. 129. The use of embodiment 128, wherein the surface modifier is moxamer. 130. Use as in embodiment 129, wherein the poloxamer is moored to poloxamer 338. 131. The use of any one of embodiments 97 to 130, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 132. The use of embodiment 131, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 μm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 133. The use of embodiment 131 or 132, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. Dv50. 134. The use of embodiment 131, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 135. The use of embodiment 131 or 134, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 136. The use of any one of embodiments 97 to 135, wherein the suspension comprises a pharmaceutically acceptable aqueous carrier, and the rilpivirine or a pharmaceutically acceptable salt thereof is suspended therein. 137. The use of any one of embodiments 97 to 136, wherein the treatment or prevention of HIV infection is treatment of HIV infection. 138. The use of any one of embodiments 97 to 137, wherein the HIV infection is HIV type 1 (HIV-1) infection. 139. The use of any one of embodiments 97 to 138, wherein the subject is a human. 140. The use of any one of embodiments 97 to 139, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is rilpivirine. 141. The use of any one of embodiments 97 to 140, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is administered by subcutaneous injection using a subcutaneous medical injection device. 142. The use of any one of embodiments 97 to 141, wherein the flow rate is constant throughout the administration process. 143. The use of any one of embodiments 97 to 142, wherein the suspension is co-administered with an HIV inhibitor of another class to the NNRTI rilpivirine. 144. Use as in embodiment 143, wherein the HIV inhibitor to which the NNRTI rilpivirine is another class is an integrase inhibitor. 145. A subcutaneous pharmaceutical injection device, comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 3 mL and Sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; A discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient ; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and from the discharge nozzle at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. Drive it out. 146. The subcutaneous medical injection device of embodiment 145, wherein the discharge nozzle has an inner diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 147. The subcutaneous medical injection device of any one of embodiments 145 to 146, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. 148. The subcutaneous medical injection device of any one of embodiments 145 to 147, wherein the discharge nozzle is an injection needle or catheter. 149. The subcutaneous medical injection device of any one of embodiments 145 to 148, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 150. The subcutaneous medical injection device of any one of embodiments 145 to 149, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 151. The subcutaneous medical injection device of any one of embodiments 145 to 150, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. 152. The subcutaneous medical injection device of any one of embodiments 145 to 150, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. 153. The subcutaneous medical injection device of any one of embodiments 145 to 152, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 154. The subcutaneous medical injection device of any one of embodiments 145 to 153, wherein the rilpivirine suspension further contains one of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. Or more. 155. The subcutaneous medical injection device of any one of embodiments 145 to 154, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 156. The subcutaneous medical injection device of embodiment 155, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. Dv90. 157. The subcutaneous medical injection device of embodiment 155 or 156, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 200 nm. Dv50 at 500 nm. 158. The subcutaneous medical injection device of embodiment 155, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 159. The subcutaneous medical injection device of embodiment 155 or 158, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. . 160. A method of administering a pharmaceutical composition using a subcutaneous injection device, the method comprising: inserting a discharge nozzle of the subcutaneous injection device into the subcutaneous layer of a patient; and causing a driver of the subcutaneous injection device to displace a volume of a suspension into a Rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles is driven from the container of the injection device and the suspension is dispensed from the suspension at a flow rate of about 0.1 mL/min to about 15 mL/min. The discharge nozzle is actuated to a volume greater than 3 mL and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in the patient for at least three months. 161. The method of embodiment 160, comprising after inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient and causing the driver of the hypodermic injection device to displace the volume of microns in suspension or Rilpivirine or a pharmaceutically acceptable salt thereof in the form of nanoparticles is driven from the container of the injection device and driven out of the discharge nozzle to enable fluid to flow between the discharge nozzle and the container of the injection device flow between. 162. The method of embodiment 160, comprising prior to inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient and causing the driver of the hypodermic injection device to displace the volume of microns in suspension or Rilpivirine or a pharmaceutically acceptable salt thereof in the form of nanoparticles is driven from the container of the injection device and driven out of the discharge nozzle to enable fluid to flow between the discharge nozzle and the container of the injection device flow between. 163. The method of any one of embodiments 160 to 162, wherein the method comprises repeating the method of embodiment 160 at intervals of at least three months. 164. The method of any one of embodiments 160 to 163, wherein the driver of the subcutaneous injection device is caused to drive the rilpivirine or pharmaceutically acceptable salt from the container of the injection device at about 0.1 mL/ The step of driving the suspension from the discharge nozzle at a flow rate of from min to about 15 mL/min is performed before settling of the rilpivirine or pharmaceutically acceptable salt thereof. 165. The method of any one of embodiments 160 to 164, wherein the discharge nozzle has an inside diameter of 23 to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 166. The method of any one of embodiments 160 to 165, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm long. 167. The method of any one of embodiments 160 to 166, wherein the discharge nozzle is an injection needle or catheter. 168. The method of any one of embodiments 160 to 167, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 169. The method of any one of embodiments 160 to 168, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 170. The method of any one of embodiments 160 to 169, wherein the subcutaneous pharmaceutical injection device is a syringe, an auto-injector, or a patch pump. 171. The method of any one of embodiments 160 to 169, wherein the subcutaneous pharmaceutical injection device includes one or more of the following: a syringe, a subcutaneous pharmaceutical infusion set, a syringe pump, and an infusion pump. 172. The method of any one of embodiments 160 to 171, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 173. The method of any one of embodiments 160 to 172, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . 174. The method of any one of embodiments 160 to 172, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 175. The method of embodiment 174, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 176. The method of embodiment 174, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv50 of about 200 nm to about 500 nm. 177. The method of embodiment 174, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 178. The method of embodiment 174, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 179. A method of preparing a subcutaneous injection device for injection, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof The salt is in the form of micron or nanoparticles in suspension, and the volume is greater than 3 mL and is sufficient to maintain therapeutic levels of the rilpivirine or pharmaceutically acceptable salt in the patient for at least three months. 180. The method of embodiment 179, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises withdrawing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. into the container of the hypodermic injection device. 181. The method of embodiment 179, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises injecting the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the hypodermic injection device. 182. The method of embodiment 179, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device comprises inserting a container into the hypodermic injection device, the container containing the volume of rilpivirine. Waring or its pharmaceutically acceptable salt. 183. The method of any one of embodiments 179 to 182, wherein the subcutaneous injection device includes a discharge nozzle sized to subcutaneously deliver the rilpivirine or a pharmaceutically acceptable salt thereof to the patient. 184. The method of embodiment 183, wherein the discharge nozzle has an inside diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 185. The method of embodiment 183 or 184, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. 186. The method of any one of embodiments 183 to 185, wherein the discharge nozzle is an injection needle or catheter. 187. The method of any one of embodiments 179 to 186, wherein the hypodermic injection device includes a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. 188. The method of embodiment 187, wherein the container comprises one of a vial, a cartridge, a syringe body, and an expandable member. 189. The method of any one of embodiments 179 to 188, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 190. The method of embodiment 189, wherein the subcutaneous medical injection device is a syringe, an auto-injector, or a patch pump. 191. The method of embodiment 189, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. 192. The method of any one of embodiments 179 to 191, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 193. The method of any one of embodiments 179 to 192, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . 194. The method of any one of embodiments 179 to 193, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 195. The method of embodiment 194, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 196. The method of embodiment 194 or embodiment 195, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. nm of Dv50. 197. The method of embodiment 194, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 198. The method of embodiment 194 or 197, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 199. A kit, comprising: a subcutaneous pharmaceutical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable drug thereof in the form of micron or nanoparticles in suspension. Acceptable salts in a volume greater than 3 mL and sufficient to maintain therapeutic levels of rilpivirine or pharmaceutically acceptable salts in patients for at least three months; Discharge nozzles sized to deliver the rilpivirine or pharmaceutically acceptable salts subcutaneously delivering a pharmaceutically acceptable salt thereof to a patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container at about 0.1 mL/min to about 15 mL/min. A flow rate of the suspension of min is driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in the suspension, The volume is greater than 3 mL and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in the patient for at least three months, and wherein the set includes a method for administering the volume of rilpivirine or a pharmaceutically acceptable salt thereof An introducer for introducing an acceptable salt into the container of the subcutaneous medical injection device. 200. The kit of embodiment 199, wherein the discharge nozzle has an inner diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 201. The kit of any one of embodiments 199 to 200, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm long. 202. The kit of any one of embodiments 199 to 201, wherein the discharge nozzle is an injection needle or a catheter. 203. The kit of any one of embodiments 199 to 202, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 204. The kit of any one of embodiments 199 to 203, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 205. The kit of any one of embodiments 199 to 204, wherein the subcutaneous pharmaceutical injection device is a syringe, an auto-injector, or a patch pump. 206. The kit of any one of embodiments 199 to 204, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. 207. The kit of any one of embodiments 199 to 206, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 208. The set of any one of embodiments 200 to 207, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. By. 209. The kit of any one of embodiments 199 to 208, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 210. The kit of embodiment 209, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. . 211. The set of embodiment 209 or 210, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. Dv50. 212. The kit of embodiment 209, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 213. The set of embodiments 209 or 212, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 214. A subcutaneous medical injection device, comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles Nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient maintaining therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and from the discharge nozzle at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. Come out. 215. The subcutaneous medical injection device of embodiment 214, wherein the discharge nozzle has an inner diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 216. The subcutaneous medical injection device of any one of embodiments 214 to 215, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. 217. The subcutaneous medical injection device of any one of embodiments 214 to 216, wherein the discharge nozzle is an injection needle or catheter. 218. The subcutaneous medical injection device of any one of embodiments 214 to 217, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 219. The subcutaneous medical injection device of any one of embodiments 214 to 218, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 220. The subcutaneous medical injection device of any one of embodiments 214 to 219, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. 221. The subcutaneous medical injection device of any one of embodiments 214 to 219, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. 222. The subcutaneous medical injection device of any one of embodiments 214 to 221, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 223. The subcutaneous medical injection device of any one of embodiments 214 to 222, wherein the rilpivirine suspension further contains one of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. Or more. 224. The subcutaneous medical injection device of any one of embodiments 214 to 223, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 225. The subcutaneous medical injection device of embodiment 224, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. Dv90. 226. The subcutaneous medical injection device of embodiment 224 or 225, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 200 nm. Dv50 at 500 nm. 227. The subcutaneous medical injection device of embodiment 224, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 228. The subcutaneous medical injection device of embodiment 224 or 227, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. . 229. A method of administering a pharmaceutical using a hypodermic injection device, the method comprising: inserting a discharge nozzle of the hypodermic injection device into the subcutaneous layer of a patient; and causing a driver of the hypodermic injection device to dispense a volume of Rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles is driven from the container of the injection device and discharged from the suspension at a flow rate of about 0.1 mL/min to about 15 mL/min. driven out of a nozzle, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, The volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months. 230. The method of embodiment 229, comprising after inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient and causing the driver of the hypodermic injection device to displace the volume of microns or nanometers in suspension. Rilpivirine or its pharmaceutically acceptable salt in the form of nanoparticles is driven from the container of the injection device and driven out of the discharge nozzle, enabling fluid to flow between the discharge nozzle and the container of the injection device. flow between. 231. The method of embodiment 229, comprising prior to inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient and causing the driver of the hypodermic injection device to displace the volume of microns or nanometers in suspension. Rilpivirine or its pharmaceutically acceptable salt in the form of nanoparticles is driven from the container of the injection device and driven out of the discharge nozzle, enabling fluid to flow between the discharge nozzle and the container of the injection device. flow between. 232. The method of any one of embodiments 229 to 231, wherein the method comprises repeating the method of embodiment 229 at intervals of at least three months. 233. The method of any one of embodiments 229 to 232, wherein the driver of the subcutaneous injection device is caused to drive the rilpivirine or pharmaceutically acceptable salt from the container of the injection device at about 0.1 mL/ The step of driving the suspension from the discharge nozzle at a flow rate of from min to about 15 mL/min is performed before settling of the rilpivirine or pharmaceutically acceptable salt thereof. 234. The method of any one of embodiments 229 to 233, wherein the discharge nozzle has an inside diameter of 23 to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 235. The method of any one of embodiments 229 to 234, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm long. 236. The method of any one of embodiments 229 to 235, wherein the discharge nozzle is an injection needle or catheter. 237. The method of any one of embodiments 229 to 236, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 238. The method of any one of embodiments 229 to 237, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 239. The method of any one of embodiments 229 to 238, wherein the subcutaneous pharmaceutical injection device is a syringe, an auto-injector, or a patch pump. 240. The method of any one of embodiments 229 to 238, wherein the subcutaneous pharmaceutical injection device includes one or more of the following: a syringe, a subcutaneous pharmaceutical infusion set, a syringe pump, and an infusion pump. 241. The method of any one of embodiments 229 to 240, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 242. The method of any one of embodiments 229 to 241, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . 243. The method of any one of embodiments 229 to 242, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 244. The method of embodiment 243, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 245. The method of embodiment 244, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv50 of about 200 nm to about 500 nm. 246. The method of embodiment 243, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 247. The method of embodiment 243 or 246, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 248. A method of preparing a subcutaneous injection device for injection, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof The salts are in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and A D _v 10 of about 300 nm to about 500 nm, and the volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months. 249. The method of embodiment 248, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises withdrawing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. into the container of the hypodermic injection device. 250. The method of embodiment 248, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises injecting the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the hypodermic injection device. 251. The method of embodiment 248, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device comprises inserting a container into the hypodermic injection device, the container containing the volume of rilpivirine. Waring or its pharmaceutically acceptable salt. 252. The method of any one of embodiments 248 to 251, wherein the subcutaneous injection device includes a discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient. 253. The method of embodiment 252, wherein the discharge nozzle has an inner diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 254. The method of embodiment 252 or 253, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. 255. The method of any one of embodiments 252 to 254, wherein the discharge nozzle is an injection needle or catheter. 256. The method of any one of embodiments 248 to 255, wherein the subcutaneous injection device includes a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. 257. The method of embodiment 256, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 258. The method of any one of embodiments 248 to 257, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 259. The method of embodiment 258, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. 260. The method of any one of embodiments 248 to 258, wherein the subcutaneous pharmaceutical injection device includes one or more of the following: a syringe, a subcutaneous pharmaceutical infusion set, a syringe pump, and an infusion pump. 261. The method of any one of embodiments 256 to 260, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 262. The method of any one of embodiments 256 to 261, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . 263. The method of any one of embodiments 248 to 262, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 264. The method of embodiment 263, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. 265. The method of embodiment 263 or embodiment 264, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. nm of Dv50. 266. The method of embodiment 263, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 267. The method of embodiment 263 or 266, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. 268. A kit, comprising: a subcutaneous pharmaceutical injection device, comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable drug thereof in the form of micron or nanoparticles in suspension. Acceptable salts, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, The volume is 2 mL or greater and is sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or pharmaceutically acceptable salt subcutaneously delivering an acceptable salt to a patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container at about 0.1 mL/min to about 15 mL/min. The flow rate of the suspension is driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in the suspension, wherein the For micron or nanoparticles having a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume is 2 mL or is larger and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt thereof in the patient for at least three months, and wherein the set includes a volume for administering that volume of rilpivirine or a pharmaceutically acceptable salt thereof The salt is introduced into the introducer of the container of the subcutaneous medical injection device. 269. The kit of embodiment 268, wherein the discharge nozzle has an inner diameter of 23 gauge to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. 270. The kit of any one of embodiments 268 to 269, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm long. 271. The kit of any one of embodiments 268 to 270, wherein the discharge nozzle is an injection needle or a catheter. 272. The kit of any one of embodiments 268 to 271, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. 273. The kit of any one of embodiments 268 to 272, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a handheld injection device. 274. The kit of any one of embodiments 268 to 273, wherein the subcutaneous medical injection device is a syringe, an auto-injector, or a patch pump. 275. The kit of any one of embodiments 268 to 273, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. 276. The kit of any one of embodiments 268 to 275, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. 277. The set of any one of embodiments 268 to 276, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. By. 278. The kit of any one of embodiments 268 to 277, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. 279. The kit of embodiment 278, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. . 280. The kit of embodiment 278 or 279, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. Dv50. 281. The kit of embodiment 278, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. 282. The kit of embodiment 278 or 281, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm.

100: syringe 110: syringe body 112: injection needle 114: plunger 200: automatic syringe 210: syringe body; syringe 212: injection needle; needle; hypodermic needle 214: drive element 220: drive 222: stopper 226: drive sleeve 227: drive spring 230: housing 241: sleeve 242: return spring 251: trigger 300: patch pump 310: expandable component 312: injection needle; needle 313: side hole 314: internal pipeline 330: housing 332: bottom side 342: Return spring 351: Injection button 400: Patch pump 410: Vial or box 412: Injection needle 413: Tubing 422: Stopper 427: Drive spring 430: Housing 432: Bottom 451: Injection button 500: Hypodermic infusion set 512: Injection needle 513: Tubing 515,516: Wings 530: Housing 600: Injection pump 610: Syringe; syringe body 613: Tubing 614: Plunger 616: Actuator 630: Syringe holder 680,681: User interface 696: Housing 700: Infusion pump 710: Storage tank 712: Infusion line 716: Pump 780: User interface 795: Power supply 796: Processor 797: Memory

The invention will be described by way of example only with reference to the accompanying drawings. [Figure 1 ]: Subcutaneous medical injection device in the form of a syringe. [Figure 2 ]: Subcutaneous medical injection device in the form of an auto-injector. [Figure 3A ]: Subcutaneous medical injection device in the form of a patch pump. [Figure 3B ]: Subcutaneous medical injection device in the form of a patch pump. [Figure 4 ] : Subcutaneous medical injection device in the form of a subcutaneous infusion set. [Figure 5 ]: Subcutaneous medical injection device in the form of a syringe pump. [Figure 6 ]: Subcutaneous medical injection device in the form of an infusion pump. Disclosure of the invention

This application has been written in chapters to improve readability. However, this does not mean that each chapter should be read independently. Instead, unless otherwise specified, each section should be read with cross-reference to other sections, i.e., the entire application as a whole. No artificial separation of embodiments is intended unless explicitly stated.

Therefore, all embodiments described herein in relation to the first aspect of the invention apply equally to the other aspects described herein, that is also in relation to/in combination with the other aspects described herein. reveal.

Claims (138)

A subcutaneous medical injection device comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in a suspension, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or the pharmaceutically acceptable salt subcutaneously to the patient; and an actuator configured to drive the rilpivirine or the pharmaceutically acceptable salt from the container and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min. The subcutaneous medical injection device of claim 1, wherein the discharge nozzle has an inner diameter of No. 21 to No. 25, especially No. 23 to No. 25, such as No. 23, No. 24, or No. 25. A subcutaneous medical injection device as described in any one of claims 1 to 2, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm. The subcutaneous medical injection device according to any one of claims 1 to 3, wherein the discharge nozzle is an injection needle or a catheter. The subcutaneous medical injection device according to any one of claims 1 to 4, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. A subcutaneous medical injection device as described in any one of claims 1 to 5, wherein the subcutaneous injection device is an on-body injection device, an off-body injection device, or a handheld injection device. The subcutaneous medical injection device as described in any one of claims 1 to 6, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. The subcutaneous medical injection device as described in any one of claims 1 to 6, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The subcutaneous medical injection device according to any one of claims 1 to 8, wherein the volume of rilpivirine or its pharmaceutically acceptable salt in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The subcutaneous medical injection device according to any one of claims 1 to 9, wherein the rilpivirine suspension further contains one of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. Or more. A subcutaneous medical injection device as described in any one of claims 1 to 10, wherein the micro- or nanoparticles have a Dv90 of about 100 nm to about 10 µm. A subcutaneous medical injection device as described in claim 11, wherein the micro- or nano-particles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micro- or nano-particles have a Dv90 of about 500 nm to about 1,600 nm. A subcutaneous medical injection device as described in claim 11 or 12, wherein the micro- or nano-particles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micro- or nano-particles have a Dv50 of about 200 nm to about 500 nm. A subcutaneous medical injection device as described in claim 11, wherein the micro- or nano-particles have a Dv90 of about 4 µm to about 6 µm. A subcutaneous medical injection device as described in claim 11 or 14, wherein the micro- or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A method of administering a pharmaceutical composition using a subcutaneous injection device, the method comprising: Insert the discharge nozzle of the hypodermic device into the patient's subcutaneous layer; and causing the driver of the hypodermic injection device to drive a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension from the container of the injection device at approximately 0.1 mL/ min to about 15 mL/min of the suspension driven from the discharge nozzle, the volume being greater than 3 mL and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months . The method of claim 16, comprising, after inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient, and causing the driver of the hypodermic injection device to displace the volume of microns in suspension. or rilpivirine or a pharmaceutically acceptable salt thereof in the form of nanoparticles, before being driven from the container of the injection device and driven out of the discharge nozzle, enabling fluid to pass between the discharge nozzle and the injection device flow between containers. The method of claim 16, comprising prior to inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient, and causing the driver of the hypodermic injection device to displace the volume of microns in suspension. or rilpivirine or a pharmaceutically acceptable salt thereof in the form of nanoparticles, before being driven from the container of the injection device and driven out of the discharge nozzle, enabling fluid to pass between the discharge nozzle and the injection device flow between containers. The method of any one of claims 16 to 18, wherein the method includes repeating the method of claim 16 at intervals of at least three months. The method according to any one of claims 16 to 19, wherein the driver of the hypodermic injection device is caused to drive the rilpivirine or pharmaceutically acceptable salt from the container of the injection device at about 0.1 mL/ The step of driving the suspension from the discharge nozzle at a flow rate of from min to about 15 mL/min is performed before settling of the rilpivirine or pharmaceutically acceptable salt thereof. A method as described in any of claims 16 to 20, wherein the discharge nozzle has an inner diameter of 21 to 25, particularly 23 to 25, such as 23, 24, or 25. The method of any one of claims 16 to 21, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. A method as claimed in any one of claims 16 to 22, wherein the discharge nozzle is an injection needle or a catheter. A method as described in any of claims 16 to 23, wherein the container comprises one of a vial, a box, a syringe body, and an expandable member. A method as described in any one of claims 16 to 24, wherein the subcutaneous injection device is a portable injection device, an extracorporeal injection device, or a handheld injection device. The method according to any one of claims 16 to 25, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. A method as described in any one of claims 16 to 25, wherein the subcutaneous medical injection device comprises one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The method according to any one of claims 16 to 27, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The method according to any one of claims 16 to 28, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . The method of any one of claims 16 to 28, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The method of claim 30, wherein the micro- or nanoparticles have a Dv90 of about 500 nm to about 6 μm, optionally wherein the micro- or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. The method of claim 30, wherein the micro- or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micro- or nanoparticles have a Dv50 of about 200 nm to about 500 nm. The method of claim 30, wherein the micro- or nano-particles have a Dv90 of about 4 µm to about 6 µm. The method of claim 30 or 33, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A method for preparing a subcutaneous injection device for injection, the method comprising: Introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension into the subcutaneous injection device, the volume being greater than 3 mL and sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months. The method of claim 35, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises drawing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of the subcutaneous injection device. The method of claim 35, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises injecting the volume of rilpivirine or a pharmaceutically acceptable salt thereof into a container of the subcutaneous injection device. The method of claim 35, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device includes inserting a container into the hypodermic injection device, the container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof Waring or its pharmaceutically acceptable salt. The method of any one of claims 35 to 38, wherein the subcutaneous injection device includes a discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient. The method of claim 39, wherein the discharge nozzle has an inner diameter of 21 to 25, particularly 23 to 25, such as 23, 24, or 25. The method of claim 39 or 40, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm. A method as described in any of claims 39 to 41, wherein the discharge nozzle is an injection needle or a catheter. The method of any one of claims 35 to 42, wherein the subcutaneous injection device comprises a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. The method of claim 43, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. The method according to any one of claims 35 to 44, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a hand-held injection device. The method of claim 45, wherein the subcutaneous drug injection device is a syringe, an automatic syringe, or a patch pump. The method of claim 45, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The method of any one of claims 35 to 47, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The method according to any one of claims 35 to 48, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . The method of any one of claims 35 to 49, wherein the micro- or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The method of claim 50, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. The method of claim 50 or claim 51, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 500 nm. nm of Dv50. The method of claim 50, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. The method of claim 50 or 53, wherein the micro- or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A set that contains: Subcutaneous medical injection device, which contains: A container configured to contain a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain the benefit in a patient. Therapeutic levels of pitirine or a pharmaceutically acceptable salt for at least three months; A discharge nozzle sized to deliver the rilpivirine or pharmaceutically acceptable salt subcutaneously to the patient; and A driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and out of the discharge nozzle at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. ;and Drug delivery device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, the volume being greater than 3 mL and sufficient to maintain the rilpivir in the patient a therapeutic level of rilpivirine or a pharmaceutically acceptable salt thereof for at least three months, and optionally wherein the set includes a device for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous medical injection device An introducer in the container, particularly wherein the set includes an introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the subcutaneous medical injection device. The kit of claim 55, wherein the discharge nozzle has an inner diameter of 21 to 25 gauge, particularly 23 to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. The set of any one of claims 55 to 56, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. A kit as described in any of claims 55 to 57, wherein the discharge nozzle is an injection needle or a catheter. The kit of any one of claims 55 to 58, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. A kit as described in any of claims 55 to 59, wherein the subcutaneous injection device is a portable injection device, an extracorporeal injection device, or a handheld injection device. The kit according to any one of claims 55 to 60, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. The set according to any one of claims 55 to 60, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The kit of any one of claims 55 to 62, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The kit of any one of claims 55 to 63, wherein the rilpivirine suspension further comprises one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifier. The kit of any one of claims 55 to 64, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The kit of claim 65, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. . The kit of claim 65 or 66, wherein the micro- or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micro- or nanoparticles have a Dv50 of about 200 nm to about 500 nm. The kit of claim 65, wherein the micro- or nano-particles have a Dv90 of about 4 µm to about 6 µm. The kit of claim 65 or 68, wherein the micro- or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A subcutaneous medical injection device comprising: a container containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles Having a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm in a volume that is 2 mL or greater and sufficient to be used in the patient maintaining therapeutic levels of rilpivirine or pharmaceutically acceptable salt for at least three months; a discharge nozzle sized to subcutaneously deliver the rilpivirine or pharmaceutically acceptable salt to the patient; and a driver , which is configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and from the discharge nozzle at a flow rate of the suspension from about 0.1 mL/min to about 15 mL/min. The subcutaneous medical injection device of claim 70, wherein the discharge nozzle has an inner diameter of 21 to 25 gauge, particularly 23 to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. The subcutaneous medical injection device according to any one of claims 70 to 71, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm. A subcutaneous medical injection device as described in any of claims 70 to 72, wherein the discharge nozzle is an injection needle or a catheter. The subcutaneous medical injection device according to any one of claims 70 to 73, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. The subcutaneous medical injection device as described in any one of claims 70 to 74, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a hand-held injection device. The subcutaneous medical injection device as described in any one of claims 70 to 75, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. A subcutaneous medical injection device as described in any one of claims 70 to 75, wherein the subcutaneous medical injection device comprises one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The subcutaneous medical injection device according to any one of claims 70 to 77, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The subcutaneous medical injection device according to any one of claims 70 to 78, wherein the rilpivirine suspension further contains one of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. Or more. The subcutaneous medical injection device according to any one of claims 70 to 79, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The subcutaneous medical injection device of claim 80, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. Dv90. The subcutaneous medical injection device of claim 80 or 81, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv10 of about 200 nm to about 200 nm. Dv50 at 500 nm. A subcutaneous medical injection device as described in claim 80, wherein the micro- or nano-particles have a Dv90 of about 4 µm to about 6 µm. A subcutaneous medical injection device as described in claim 80 or 83, wherein the micro- or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A method of administering pharmaceuticals using a hypodermic injection device, the method comprising: inserting a discharge nozzle of the hypodermic injection device into the subcutaneous layer of a patient; and causing a driver of the hypodermic injection device to inject a volume of micron or micron in suspension Rilpivirine or a pharmaceutically acceptable salt thereof in the form of nanoparticles is driven from the container of the injection device and from the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min. out, wherein the micron or nanoparticles have a _Dv 90 of about 4 µm to about 6 µm, a _Dv 50 of about 1.5 µm to about 2 µm, and _{a Dv} 10 of about 300 nm to about 500 nm, the volume is 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months. The method of claim 85, comprising, after inserting the discharge nozzle of the hypodermic injection device into the subcutaneous layer of the patient, and causing the driver of the hypodermic injection device to displace the volume of microns or nanometers in suspension. Rilpivirine or its pharmaceutically acceptable salt in the form of nanoparticles is driven from the container of the injection device and driven out of the discharge nozzle, enabling fluid to flow between the discharge nozzle and the container of the injection device. flow between. A method as described in claim 85, comprising allowing fluid to flow between the discharge nozzle and the container of the injection device before inserting the discharge nozzle of the subcutaneous injection device into the subcutaneous layer of the patient and before causing the actuator of the subcutaneous injection device to drive the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles suspended in a liquid from the container of the injection device and out of the discharge nozzle. The method of any one of claims 85 to 87, wherein the method includes repeating the method of claim 85 at intervals of at least three months. A method as described in any one of claims 85 to 88, wherein the step of causing the actuator of the subcutaneous injection device to drive the rilpivirine or the pharmaceutically acceptable salt from the container of the injection device and out of the discharge nozzle at a flow rate of the suspension of about 0.1 mL/min to about 15 mL/min is performed before the rilpivirine or the pharmaceutically acceptable salt thereof settles. The method of any one of claims 85 to 89, wherein the discharge nozzle has an inner diameter of 21 to 25 gauge, in particular 23 to 25 gauge, such as 23 gauge, 24 gauge, or 25 gauge. The method of any one of claims 85 to 90, wherein the discharge nozzle has a length from 12.7 mm to about 19.1 mm. A method as claimed in any one of claims 85 to 91, wherein the discharge nozzle is an injection needle or catheter. The method of any one of claims 85 to 92, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. A method as described in any one of claims 85 to 93, wherein the subcutaneous injection device is a portable injection device, an extracorporeal injection device, or a handheld injection device. The method according to any one of claims 85 to 94, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. The method of any one of claims 85 to 94, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The method according to any one of claims 85 to 96, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The method according to any one of claims 85 to 97, wherein the rilpivirine suspension further contains one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifying agent. . The method of any one of claims 85 to 98, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The method of claim 99, wherein the micro- or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micro- or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. The method of claim 100, wherein the micron or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micron or nanoparticles have a Dv50 of about 200 nm to about 500 nm. The method of claim 99, wherein the micro- or nanoparticles have a Dv90 of about 4 µm to about 6 µm. The method of claim 99 or 102, wherein the micro- or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A method for preparing a subcutaneous injection device for injection, the method comprising: introducing a volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device, the rilpivirine or a pharmaceutically acceptable salt thereof being in the form of micro- or nanoparticles in suspension, wherein the micro- or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, and the volume is 2 mL or greater and is sufficient to maintain a therapeutic level of the rilpivirine or the pharmaceutically acceptable salt in a patient for at least three months. The method of claim 104, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises withdrawing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the hypodermic injection device. The method of claim 104, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous injection device comprises injecting the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the container of the hypodermic injection device. The method of claim 104, wherein introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the hypodermic injection device includes inserting a container into the hypodermic injection device, the container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof Waring or its pharmaceutically acceptable salt. The method of any one of claims 104 to 107, wherein the subcutaneous injection device comprises a discharge nozzle sized to deliver the rilpivirine or a pharmaceutically acceptable salt subcutaneously to the patient. The method of claim 108, wherein the discharge nozzle has an inner diameter of 21-25, particularly 23-25, such as 23, 24, or 25. The method of claim 108 or 109, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm. The method of any one of claims 108 to 110, wherein the discharge nozzle is an injection needle or catheter. The method of any one of claims 104 to 111, wherein the subcutaneous injection device comprises a container containing the volume of rilpivirine or a pharmaceutically acceptable salt thereof. The method of claim 112, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. The method of any one of claims 104 to 113, wherein the subcutaneous injection device is a body-worn injection device, an extracorporeal injection device, or a hand-held injection device. The method of claim 114, wherein the subcutaneous medical injection device is a syringe, an automatic injector, or a patch pump. The method of any one of claims 104 to 114, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The method of any one of claims 112 to 116, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The method of any one of claims 112 to 117, wherein the rilpivirine suspension further comprises one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifier. The method of any one of claims 104 to 118, wherein the micron or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The method of claim 119, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. The method of claim 119 or claim 120, wherein the micro- or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micro- or nanoparticles have a Dv50 of about 200 nm to about 500 nm. The method of claim 119, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. The method of claim 119 or 122, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm. A kit comprising: a subcutaneous pharmaceutical injection device comprising: a container configured to contain a volume of rilpivirine or a pharmaceutically acceptable formulation thereof in the form of micron or nanoparticles in suspension salt, wherein the micron or nanoparticles have a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume is 2 mL or greater and sufficient to maintain therapeutic levels of rilpivirine or a pharmaceutically acceptable salt in the patient for at least three months; a discharge nozzle sized to deliver the rilpivirine or pharmaceutically acceptable salt subcutaneously delivering the received salt to the patient; and a driver configured to drive the rilpivirine or pharmaceutically acceptable salt from the container and displace the suspension at about 0.1 mL/min to about 15 mL/min. a flow rate of liquid driven from the discharge nozzle; and a drug delivery device containing a volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micron or nanoparticles in suspension, wherein the micron or nanoparticles having a D _v 90 of about 4 µm to about 6 µm, a D _v 50 of about 1.5 µm to about 2 µm, and a D _v 10 of about 300 nm to about 500 nm, the volume being 2 mL or greater and sufficient to maintain the therapeutic level of rilpivirine or a pharmaceutically acceptable salt thereof in the patient for at least three months, and optionally wherein the set includes a method for administering the volume of rilpivirine or a pharmaceutically acceptable salt thereof An introducer for introducing the salt into the container of the subcutaneous medical injection device, particularly wherein the set includes the introducer for introducing the volume of rilpivirine or a pharmaceutically acceptable salt thereof into the subcutaneous medical injection device. Importer in the container. A kit as described in claim 124, wherein the discharge nozzle has an inner diameter of 21-25, particularly 23-25, such as 23, 24, or 25. A kit as described in any of claims 124 to 125, wherein the discharge nozzle has a length of 12.7 mm to about 19.1 mm long. A kit as described in any of claims 124 to 126, wherein the discharge nozzle is an injection needle or a catheter. The kit of any one of claims 124 to 127, wherein the container includes one of a vial, a cartridge, a syringe body, and an expandable member. The kit according to any one of claims 124 to 128, wherein the hypodermic injection device is a body-worn injection device, an extracorporeal injection device, or a hand-held injection device. The kit according to any one of claims 124 to 129, wherein the subcutaneous medical injection device is a syringe, an auto-injector, or a patch pump. The set according to any one of claims 124 to 129, wherein the subcutaneous medical injection device includes one or more of the following: a syringe, a subcutaneous medical infusion set, a syringe pump, and an infusion pump. The kit of any one of claims 124 to 131, wherein the volume of rilpivirine or a pharmaceutically acceptable salt thereof in the form of micro- or nanoparticles in suspension is greater than 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL. The kit of any one of claims 124 to 132, wherein the rilpivirine suspension further comprises one or more of a buffer, a pH adjuster, an isotonic agent, a chelating agent, and a surface modifier. The kit of any one of claims 124 to 133, wherein the micro- or nanoparticles have a Dv90 of about 100 nm to about 10 µm. The kit of claim 134, wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 6 µm, optionally wherein the micron or nanoparticles have a Dv90 of about 500 nm to about 1,600 nm. . The kit of claim 134 or 135, wherein the micro- or nanoparticles have a Dv10 of about 75 nm to about 200 nm, and/or wherein the micro- or nanoparticles have a Dv50 of about 200 nm to about 500 nm. The kit of claim 134, wherein the micron or nanoparticles have a Dv90 of about 4 µm to about 6 µm. The kit of claim 134 or 137, wherein the micron or nanoparticles have a Dv10 of about 300 nm to about 500 nm, and/or wherein the particles have a Dv50 of about 1.5 µm to about 2 µm.

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