CN111110634A - Chloroquine phosphate inhalation aerosol and preparation method thereof - Google Patents
Chloroquine phosphate inhalation aerosol and preparation method thereof Download PDFInfo
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- CN111110634A CN111110634A CN202010106332.3A CN202010106332A CN111110634A CN 111110634 A CN111110634 A CN 111110634A CN 202010106332 A CN202010106332 A CN 202010106332A CN 111110634 A CN111110634 A CN 111110634A
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
- A61K9/124—Aerosols; Foams characterised by the propellant
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Abstract
The invention belongs to the technical field of medicines, and discloses chloroquine phosphate inhalation aerosol and a preparation method thereof. The chloroquine phosphate inhalation aerosol is composed of an active ingredient chloroquine phosphate, a propellant, a flavoring agent, a pH regulator, water for injection and the like in a certain proportion, and the aerosol inhalation is administrated through an oral cavity, directly acts on the lung and realizes targeted administration. The inhalation preparation of the invention can target focus, has accurate dosage and quick effect, can quickly improve the pulmonary infection condition, is beneficial to improving the adaptability of an infected person, simultaneously avoids absorption through gastrointestinal tract and reduces the side effect of the gastrointestinal tract.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to chloroquine phosphate inhalation aerosol and a preparation method thereof.
Background
Aiming at 2019-nCoV, no specific antiviral drug exists at present all over the world, the specific antiviral drug is mainly used for symptomatic treatment of symptoms of patients, no effective antiviral drug exists, and a proper antiviral drug needs to be quickly found according to the current epidemic situation, so that the medicine has important significance for treating infectors, controlling epidemic spread and reducing fatality rate at a reasonable medicine application time.
2019-nCoV virus and SARS coronavirus have similar receptor binding path, and through the molecular mechanism of the binding interaction of S-protein and human ACE2 receptor, ACE2 exists in pulmonary alveoli and small intestine epithelial cells, and is expressed on the surfaces of arteriovenous epithelial cells and arterial smooth muscle cells of all organs, wherein the respiratory tract epithelial cells are distributed most, so that the respiratory tract and the lung are most susceptible to infection.
By analyzing the symptoms of patients, the symptoms of upper respiratory tract such as nasal obstruction, nasal discharge, sore throat and the like are not obvious, and the 2019-nCoV virus of the upper respiratory tract (including nasopharynx part and oropharynx part) of most patients is negative in detection, and the 2019-nCoV virus can be detected only by collecting alveolar lavage fluid, which shows that the virus has extremely high affinity to lung, so that the medicine needs to directly reach a target point, namely alveolus.
Chloroquine phosphate is a drug for the treatment of malaria and autoimmune diseases and has been used clinically for over 70 years. Previous research shows that chloroquine phosphate has antimalarial effect and broad-spectrum antiviral and immunoregulatory effect, and is used mainly in treating chloroquine sensitive malignant malaria, vivax malaria and malaria quartana, preventing malaria, treating intestinal amebiasis, connective tissue disease, photosensitive diseases (such as erythema solare), etc. Mechanistically, chloroquine blocks viral infection by increasing the endosomal pH required for virus/cell fusion. In 2004, in a study on SARS virus, foreign scientists claimed that chloroquine could inhibit SARS virus replication in vitro. And scientific research institutions in China at recent years also show that chloroquine can effectively inhibit the replication of the novel coronavirus at the cellular level.
It has been found that the new coronavirus enters human cell membrane by binding to ACE2 receptor of human cell through S protein. And chloroquine can change the structure of a new coronavirus entering a human cell receptor ACE2 or inhibit the combination of a virus surface S protein and ACE2, so that the virus is inhibited from propagating in a human body. Mention is made in the "guidelines for rapid diagnosis and treatment of pneumonia infected with novel coronavirus (2019-nCoV) (sixth edition): chloroquine phosphate tablets, 500mg for an adult, 2 times per day, are contemplated. Therefore, the chloroquine phosphate inhalant is possibly the first micromolecule compound inhalant for treating the coronavirus, is directly targeted to the lung for administration, quickly takes effect and improves the cure rate of patients.
The aerosol is a mixed solution of a drug-containing solution or suspension and a proper propellant, which are jointly packaged in a pressure-resistant container with a special valve system, and when the aerosol is used, the content is sprayed out in a fine mist shape by the pressure of the propellant, and a patient actively inhales the aerosol to play a local or systemic treatment role.
The inhalation aerosol has the advantages that the inhalation aerosol can not be replaced by other formulations and has a certain position in clinical treatment, the advantages of the aerosol mainly comprise ① having quick-acting and positioning effects, for example, the aerosol for treating asthma can enable drug particles to directly enter the lung, the aerosol can show effect after being inhaled for 2min, ② drugs can be sealed in a container to keep clean and aseptic drugs, the container is light-tight and is not in direct contact with oxygen and moisture in the air, so that the stability of the drugs is improved, ③ drugs can be prevented from being damaged by gastrointestinal tracts and liver first pass effect after being absorbed by the lung, ④ can accurately control the dose by using a quantitative valve, and ⑤ is convenient to use.
Although aerosols have the above advantages, the formulations contain propellants as the driving force for the drug in the aerosol. Common propellants are both chlorofluorocarbons (CFC, freon) and Hydrofluorocarbons (HFA). Due to the depletion of the ozone layer and the environmental impact of CFCs, the montreal convention in 1997 mandates that countries prohibit the use of such propellants and refrigerants in 2003.
The physical and chemical properties of the new propellant Hydrofluoroalkane (HFA), such as properties and boiling point, are similar to those of CFC with low boiling point, and the HFA which does not damage the atmospheric ozone layer because of no chlorine is gradually used. Currently, the HFA propellants used in foreign countries are tetrafluoroethane (HFA-314a) and heptafluoropropane (HFA-277).
Chloroquine Phosphate (Chloroquine Phosphate) is white crystalline powder, odorless, bitter, and light-sensitive, and the aqueous solution is acidic (pH about 4.5). The chloroquine phosphate is completely taken orally, the Tmax is 1-2 h, the blood concentration is maintained for a long time, and the half-life period is 2.5-10 days. The concentration of chloroquine in erythrocytes is 10-20 times of that in blood plasma, chloroquine is more combined with tissue protein, and the concentration in liver, spleen, kidney and lung is 200-700 times higher than that in blood plasma. The metabolic conversion of chloroquine in vivo is carried out in the liver, and the main metabolite is the deethylchloroquine, which still has antimalarial effect.
The product is easily dissolved in water and has good permeability, and belongs to BCS1 class drugs. Meanwhile, the blood concentration is maintained for a long time, the half-life period is long and is about 2.5-10 days, the main metabolite of the compound is the deethylchloroquine, and the compound still has an active effect. The chloroquine phosphate has high pulmonary affinity, and the pulmonary concentration is far higher than that in blood plasma, so that the chloroquine phosphate is very suitable for being used for preparing pulmonary inhalation preparations for treating pulmonary virus infection.
The invention discloses a chloroquine phosphate inhalation aerosol, which takes water for injection as a solvent, adds a flavoring agent to improve the problem of bitter taste of active ingredients, simultaneously adds a pH regulator to change the pH of the liquid medicine to reduce the irritation of pulmonary administration, is designed into a quantitative aerosol, can fill the liquid medicine into a sealed pressure-resistant container, and avoids the instability of the liquid medicine when exposed to light. The aerosol directly acts on alveolus, and has the advantages of short material exchange distance, high speed, good lipid solubility of main drug, and rapid onset of drug action due to large lung absorption surface area, abundant capillary network, and thin cell layer of alveolus epithelium.
Disclosure of Invention
Aiming at the existing problems, the invention provides a chloroquine phosphate inhalation aerosol with a novel administration mode, which has the characteristics of good stability, small toxic and side effect and convenient use and carrying, and can be directly administrated by lung through a respiratory tract.
The invention aims to provide a chloroquine phosphate inhalation and a preparation method thereof.
Specifically, the invention provides a chloroquine phosphate inhalation aerosol, which consists of the following components: a) an active agent; b) a propellant; c) a flavoring agent; d) a pH adjusting agent; e) water for injection.
The particle diameter (calculated by volume) D of the active ingredient10≤2μm，D50≤4μm，D90≤6μm。
The propellant comprises one or more HFAs (high frequency ethers) such as tetrafluoroethane, pentafluoroethane, hexafluoroethane, heptafluoroethane and heptafluoropropane, and is preferably tetrafluoroethane and/or heptafluoropropane.
The flavoring agent is added into the prescription to mainly improve the discomfort caused by bitter taste of the active ingredients and improve the compliance of patients. The flavoring agent is one or mixture of sodium cyclamate, sucralose, xylitol, fructose, cassia oil, sweet orange oil, menthol, orange essence and lemon volatile oil.
The liquid medicine with the dissolved active ingredients is acidic, so that the pulmonary administration has certain irritation, and the pH regulator is added into the prescription to improve the pH of the liquid medicine. The pH regulator is one or more of buffer salt system mixture including citric acid-sodium citrate, phosphoric acid-sodium phosphate, citric acid-sodium citrate, hydrochloric acid-sodium hydroxide, etc. The inhalant consists of the following raw and auxiliary materials in parts by weight:
the preparation method of chloroquine phosphate inhalation aerosol is characterized by comprising the following steps:
1, a) carrying out micronization on chloroquine phosphate by grinding and crushing (a free-flow mill, a ball mill), spray drying and the like;
b) adding a flavoring agent into water for injection, slowly adding micronized chloroquine phosphate, stirring and continuing until a clear transparent solution is formed, adjusting the pH to about 7 by using a hydrochloric acid-sodium hydroxide solution, and adding the solution into a pressure-resistant container;
c) and (3) inserting a valve into the pressure-resistant container, sealing the valve and filling the propellant to obtain the propellant.
Compared with the prior art, the invention has the following advantages:
(1) the chloroquine phosphate inhalation aerosol has the advantages of good stability, accurate dosage, simple use, convenient carrying and good tolerance of patients. The particle size of the liquid drops sprayed by the spray gun is about 1-5 mu m, and the spray gun has good lung deposition. The medicine can reach the lung of a patient quickly by directly feeding the medicine to the lung, avoids first-pass effect, reduces side effect, has high local concentration and can better play a role in the body.
(2) The chloroquine phosphate inhalation aerosol adopts a pressure-resistant container aluminum can, ensures that the medicine is sterile and is stored in a dark place without being influenced by illumination and moisture, and greatly improves the stability of the medicine.
(3) The chloroquine phosphate adopts a novel propellant HFA, so that the ozone layer is not damaged, and the environment is not influenced.
Detailed Description
The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
EXAMPLE 1 Chloroquine phosphate micronization
Micronizing chloroquine phosphate in a jet mill under the crushing pressure of 0.4-1.2 MPa to obtain a product with a particle size D50≤3μm，D90≤5μm。
Example 2:
chloroquine phosphate 5.0g
Water for injection 100.0g
HFA-134a was supplemented to 1000.0g
The preparation method comprises the following steps: dissolving in water for injection under stirring, slowly adding the micronized active drug obtained in example 1, stirring and continuing until a clear transparent solution is formed, and adding into a pressure-resistant container; and (3) inserting a valve into the pressure-resistant container, sealing the valve and filling the propellant to obtain the propellant.
Example 3:
the preparation method comprises the following steps: adding a flavoring agent into water for injection, stirring for dissolving, slowly adding the micronized active drug obtained in example 1, stirring and continuing until a clear transparent solution is formed, and adding into a pressure-resistant container; and (3) inserting a valve into the pressure-resistant container, sealing the valve and filling the propellant to obtain the propellant.
Example 4:
the preparation method comprises the following steps: adding a flavoring agent into water for injection, stirring for dissolving, slowly adding the micronized active drug obtained in example 1, stirring and continuing until a clear transparent solution is formed, adjusting the pH value of the liquid medicine to 7 by using a proper amount of hydrochloric acid-sodium hydroxide, and adding the liquid medicine into a pressure-resistant container; and (3) inserting a valve into the pressure-resistant container, sealing the valve and filling the propellant to obtain the propellant. Example 1 micronized active drug particle size distribution evaluation
The droplet size distribution was determined by laser diffraction using a Mastersizer3000(Malvern Instruments, Worcs, UK). The powder was redispersed by measuring with 4bar compressed air by a Scirocco3000 aerosol feeder (Malvern Instruments, Worcs, UK). All measurements were performed in triplicate cycles.
Table 1 example 1 micronized active drug particle size distribution
| D10 | D50 | D90 | |
| Average particle diameter (μm) | 2.03 | 3.75 | 5.23 |
| Standard deviation (%) | 0.11 | 0.07 | 0.05 |
Example 2-3 evaluation of droplet size distribution and in vitro Lung deposition Rate
The "lung deposition rate" of the active ingredient according to the invention, as reflected by the fine particle dose (FPF), is an important parameter for evaluating the quality of an inhaled formulation, as the ratio of the mist distribution in the 2-7 stages is comparable to the lung deposition rate of the active ingredient when the gas flow reaches 60L/min, for example. The fine particle dose (FPF) is the percentage of the dose of fine drug particles in the inhalant to the indicated amount and can be determined by an in vitro device (see "0951 fine particle aerodynamic properties determination for inhalant formulation" in the fourth part of the chinese pharmacopoeia 2015). The mist particle distribution and the shot dose were measured using a New Generation Impactor (NGI), a device available from COPLEY, UK, at a flow rate of 60L/min for 4s per suction time, and the amount of the 2 nd to 7 th-order (aerodynamic particle size range: 0.34 to 4.46 μm) collecting pan was counted as the total amount of mist particle distribution.
TABLE 2 droplet size distribution, evacuation rate and in vitro lung deposition rate for samples of examples 2-3
Compared with the comparative examples 2-4, the addition of the flavoring agent and the pH regulator has no obvious influence on the particle size distribution and the lung deposition rate of the fogdrops.
Examples 2-4 stability Studies
Samples of examples 2-3 were placed under accelerated conditions (40 ℃/RH 75%) and long-term conditions (25 ℃/RH 65%) for 1 month, then samples were taken to determine the related substances, the impurity content was counted, and the variation trend of the impurities was judged, with the following results:
TABLE 3 examples 2-4 sample stability
Compared with the examples 2-3, the addition of the pH regulator provides better stability.
Claims (9)
1. An inhalation aerosol of chloroquine phosphate, which is characterized in that the aerosol consists of the following components: chloroquine phosphate, a propellant, a flavoring agent, a pH regulator and water for injection.
2. The chloroquine phosphate inhalation aerosol of claim 1, wherein the chloroquine phosphate has a particle size (volume-based particle size Dv) D10≤2μm，D50≤4μm，D90≤6μm。
3. The chloroquine phosphate inhalation aerosol of claim 1 or 2, wherein the chloroquine phosphate comprises 0.1 to 2% by weight of the total weight of the medicament, preferably 0.2 to 1% by weight of the total weight of the medicament.
4. The chloroquine phosphate inhalation aerosol as claimed in claim 1, wherein the propellant comprises one or more HFA (high frequency absorption agents) such as tetrafluoroethane, pentafluoroethane, hexafluoroethane, heptafluoroethane and heptafluoropropane, preferably tetrafluoroethane and/or heptafluoropropane.
5. The chloroquine phosphate inhalation aerosol of claim 4, wherein the propellant comprises 50 to 99%, preferably 90 to 99% of the total weight of the medicament.
6. The chloroquine phosphate inhalation aerosol of any one of claims 1, 2 and 4, wherein the flavoring agent comprises one or a mixture of sodium cyclamate, sucralose, xylitol, fructose, cassia oil, sweet orange oil, menthol, orange essence and lemon volatile oil.
7. The chloroquine phosphate inhalation aerosol of claim 6, wherein said flavoring agent is not more than 1% by weight of the total weight of the medicament.
8. The chloroquine phosphate inhalation aerosol as claimed in any one of claims 1, 2, 4, 6 and 7, wherein the pH regulator comprises one or more buffer salt systems selected from citric acid-sodium citrate, phosphoric acid-sodium phosphate, citric acid-sodium citrate, hydrochloric acid-sodium hydroxide, etc.
9. A process for the preparation of an inhalation aerosol formulation of chloroquine phosphate according to any of claims 1 to 9, comprising the steps of:
a) micronizing chloroquine phosphate by grinding and crushing (energy flow mill, ball mill), spray drying and the like;
b) adding a flavoring agent into water for injection, slowly adding micronized chloroquine phosphate, stirring and continuing until a clear transparent solution is formed, adjusting the pH to about 7 by using a hydrochloric acid-sodium hydroxide solution, and adding the solution into a pressure-resistant container;
c) and (3) inserting a valve into the pressure-resistant container, sealing the valve and filling the propellant to obtain the propellant.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010106332.3A CN111110634A (en) | 2020-02-20 | 2020-02-20 | Chloroquine phosphate inhalation aerosol and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022053693A1 (en) * | 2020-09-14 | 2022-03-17 | Philip Morris Products S.A. | Pharmaceutical composition comprising chloroquine and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080319010A1 (en) * | 2005-11-09 | 2008-12-25 | St. Jude Children's Research Hospital | Use of Chloroquine to Treat Metabolic Syndrome |
| CN104800214A (en) * | 2014-01-27 | 2015-07-29 | 成都英诺新科技有限公司 | Roflumilast inhalation aerosol compound and preparation method thereof |
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- 2020-02-20 CN CN202010106332.3A patent/CN111110634A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080319010A1 (en) * | 2005-11-09 | 2008-12-25 | St. Jude Children's Research Hospital | Use of Chloroquine to Treat Metabolic Syndrome |
| CN104800214A (en) * | 2014-01-27 | 2015-07-29 | 成都英诺新科技有限公司 | Roflumilast inhalation aerosol compound and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李司坤: "对抗新冠病毒我们有什么药", 《环球时报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022053693A1 (en) * | 2020-09-14 | 2022-03-17 | Philip Morris Products S.A. | Pharmaceutical composition comprising chloroquine and uses thereof |
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Address after: 211100 building 7, life science and Technology Innovation Park, 568 longmian Avenue, Jiangning District, Nanjing City, Jiangsu Province Applicant after: Jiangsu ailikang Pharmaceutical Technology Co.,Ltd. Address before: 211100 building 7, life science and Technology Innovation Park, 568 longmian Avenue, Jiangning District, Nanjing City, Jiangsu Province Applicant before: JIANGSU ALICORN PHARMACEUTICAL Co.,Ltd. |
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