JP2013500984A - Combination of dapsone and adapalen - Google Patents

Abstract

  Contains at least two active ingredients for effective treatment of acne and other skin conditions, one of which is dapsone and one selected from the group consisting of adapalene, tazarotene and traininion A composition suitable for topical application.

Description

CROSS-REFERENCE This application claims the benefit of, filed July 30, 2009 U.S. Provisional Patent Application No. 61 / 229,903, the disclosure of its entirety by this specific reference, herein Incorporated.
Field of Invention

  The present invention relates to compositions and methods for the treatment of acne vulgaris and other skin conditions.

BACKGROUND OF THE INVENTION Acne is the most common skin disease that affects a large number of adolescents and young adults after reaching puberty. Although it is not a life-threatening disease, it has a psychological effect on the patient. Chronic inflammatory acne can also cause permanent scarring on the face.

  There are several factors that contribute to the formation of acne lesions, including: 1. excessive sebum production as a result of pubertal hormonal changes; 2. Colonization of Propionibacterium acnes in the follicular sebaceous unit 3. Hyperkeratosis or abnormal desquamation of the epithelium (upper sebaceous glands) of the upper follicle resulting in blockage of the follicular sebaceous duct; Formation of inflammatory molecules as a result of acne activity on sebaceous lipids.

  Occlusion and inflammation of the follicular sebaceous duct caused by inflammatory metabolites formed by Acne bacteria results in the formation of comedones. Excess sebum production as a result of pubertal hormonal changes, combined with increased epithelial turnover of the upper follicle, leads to the formation of microcomedones, which progress to acne inflammatory papules and pustules. The combination of lipid-rich sebum and protein-rich desquamated cells provides an ideal environment for the growth and activity of acne bacteria that convert sebaceous gland lipids into inflammatory free fatty acid molecules. Brought about. Patients may have a combination thereof, either non-inflammatory (open and closed comedones), inflammatory (papules and pustules), or in most cases. In general, for most patients, local treatment is sufficient to control acne lesions.

  Because acne is a multifactorial symptom, when it is treated, commercial products act on one or more of the basic factors that contribute to acne. There are many prescription and over-the-counter (OTC) products available for the treatment of acne, but they all lack the desired efficacy or tolerability, or both. Currently available products include antibiotics (local and systemic), benzoyl peroxide, retinoids (local and systemic), dapsone, and several other compounds.

  Dapsone, an anti-acne molecule, is commercially available as a commercial product, Zone. Aczone® is a 5% dapsone gel with a rough texture due to the insoluble particles of the dapsone drug. Dapsone insolubility limits dapsone bioavailability upon application and upon its absorption through the skin and is therefore administered twice daily. At the biochemical and molecular level, dapsone exhibits anti-inflammatory activity that provides a unique mechanism of action of this molecule in the treatment of inflammatory acne lesions. However, the mechanism of this action is not fully understood. A complex combination of inflammatory pathways produces the clinical inflammation observed in acne. Neutrophils are known to contribute significantly to inflammatory acne. Dapsone is known to suppress neutrophil recruitment and local production of toxic products, thereby inhibiting neutrophil chemotaxis and reducing oxygen free radical production. It further inhibits the release of lysosomal enzymes, decreases the release and prevents the inflammatory effects of prostaglandins and leukotrienes. These effects lead to a reduction in inflammatory acne lesions. In addition to its anti-inflammatory activity, dapsone is also effective against acne bacteria. The MIC90 for Acne is 8 μg / mL.

Adapalene is a third generation retinoid, a compound related to vitamin A, and has been approved by the FDA for the treatment of acne. Adapalene is known to alleviate the inflammatory process, but its mechanism of action is also not fully understood. Adapalene products are sold at concentrations of 0.1% and 0.3% w / v for gels and 0.1% w / v for creams. Adapalene acts on the retinoid receptor and appears to be a modulator of cell differentiation, keratinization, and inflammatory processes involved in the pathology of acne vulgaris. The absorption of adapalene from either 0.1% or 0.3% gels or creams is low. In one pharmacokinetic study, 16 patients with acne vulgaris received 0.3% adapalene gel at a dose of about 2 mg / cm 2 applied to the face, chest, and back. . Fifteen patients produced quantifiable (LOQ = 0.1 ng / mL) adapalene levels with a mean C _max of 0.553 ± 0.466 ng / mL on day 10 of treatment. The mean AUC _0-24hr determined in 15 of 16 patients on day 10 was 8.37 ± 8.46 ng. h / mL. Apparent terminal half-life determined in 15 of 16 patients ranged from 7 to 51 hours, with an average of 17.2 ± 10.2 hours. Adapalene was quickly removed from the plasma and was not detected after 72 hours of the last application for all but one subject.

  Products currently available for the treatment of acne vulgaris lack the desired efficacy and / or have side effects or tolerability problems that are undesirable for the subject, and therefore for products that are effective for the treatment of acne vulgaris, There are unmet consumer needs.

  Combination acne products may offer enhanced efficacy benefits compared to products containing a single active agent by utilizing a synergistic mechanism of action of active agents for the treatment of acne. I will. The present invention is directed to acne products comprising at least two active compounds, in particular acne vulgaris, rosacea, atopic dermatitis, treatment of chronic wounds, acne, keratosis pillaris, Cosmetic improvement of psoriasis, surgery and acne scars, sebaceous cysts, inflammatory skin diseases, post-inflammatory pigmentation, eczema, dryness, pruritus, lichen planus, nodular urticaria, eczema and rash, and other A combination preparation of dapsone and adapalene for use in the treatment of skin symptoms such as skin symptoms is targeted.

Some embodiments of the invention include the following items:
1) A dermatological composition comprising dapsone, adapalene, and water.
2) The skin according to paragraph 1, wherein the composition comprises 5% w / w dapsone and 0.1% or 0.3% w / w adapalene and is used for the treatment of acne vulgaris Medical composition.
3) The dermatological composition according to item 2, wherein the composition is 0.5% w / w dapsone and 0.3% w / w adapalene.
4) The dermatological composition according to item 1, wherein the composition is a gel.
5) The composition comprises 0.5% w / w dapsone, 0.1% w / w adapalene, 1.5% w / w benzyl alcohol, Transcutol, 5-25% w / w PEG400, 5. A composition according to paragraphs 1 and 4 which is 0.01% w / w EDTA and 0.03% w / w citric acid.
6) The composition according to paragraphs 1-5, wherein the composition further comprises 1-4% w / w of hydroxyethyl cellulose.
7) A composition according to paragraphs 1-5, further comprising 0.5-2% w / w Carbopol 980.
8) The composition according to items 1 to 7, further comprising methylparaben.
9) The composition according to items 1 to 8, further comprising lactic acid.
10) The composition according to any one of Items 1 to 9, further comprising glycerin.
11) The composition of paragraph 5, further comprising 5-15% w / w dimethyl isosorbide.
12) The composition of paragraphs 1-5, wherein Transcutol is present in an amount of 25% w / w.
13) The composition according to paragraphs 1 to 12, wherein a buffer selected from the group consisting of NaOH, trolamine, and hydrochloric acid is added to adjust the pH.
14) The composition according to any one of items 1 to 13, wherein the pH of the composition is 5.5.
15) The composition according to items 1 to 5, further comprising 2-3% of hydroxyethyl cellulose.
16) In paragraphs 1-15, wherein the composition is one form selected from the group consisting of gels, emulsions, creams, liquids, pastes, lotions, nanoemulsions, microemulsions, inverse emulsions, and liposomal creams. The composition as described.
17) The composition comprises acne vulgaris, rosacea, atopic dermatitis, treatment of chronic wounds, pressure ulcers, pore keratosis, sebaceous cysts, inflammatory skin diseases, post-inflammatory pigmentation, eczema, dryness , Which can be used for one treatment selected from the group consisting of pruritus, lichen planus, nodular rash, dermatitis, eczema, and rash, and other skin symptoms, Composition.
18) A method for treating acne vulgaris by applying the composition according to any one of items 1 to 17.
19) The method of treatment according to paragraph 17, wherein the application is once a day.
20) The method of treatment according to paragraph 17, wherein the application is twice a day.

Intended for dapsone and adapalene formulations for the treatment of skin conditions. A variation of the formulation for the treatment of skin symptoms of formula 1 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 2 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 2 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 2.1 in FIG. A variation of the formulation for the treatment of skin symptoms of formula 2.1 in FIG. A variation of the formulation for the treatment of skin symptoms of formula 4 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 4 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 4 in FIG. 1 is intended. A variation of the formulation for the treatment of skin symptoms of formula 4 in FIG. 1 is intended. Intended for dapsone and adapalene formulations for the treatment of skin conditions.

  The present invention is directed to topical compositions for the treatment of skin conditions that contain at least two active ingredients for the effective treatment of acne and other skin conditions such as rosacea, and these One of them is Dapsone and the other (or more) is selected from the following list.

Some broad embodiments and possible combinations of the invention are found below.
Suitable compounds that can be combined with dapsone (2-10% w / w) include:
1. Agents with bactericidal and / or comedolytic properties:
a. Benzoyl peroxide (2.5-10% w / w), and b. Other antibacterial active substances that are effective against acne.
2. Agents that inhibit comedone formation by reducing blockage of the follicular sebaceous duct or have keratolytic properties such as:
a. Salicylic acid (0.5-3% w / w),
b. Azelaic acid (up to 20% w / w),
c. Sulfacetamide-sulfur (5-10% w / w), and d. Other keratolytic agents.
3. Drugs that decrease sebaceous gland secretion and cause epithelial desquamation:
a. Retinoids:
i. Tretinoin or trans retinoic acid (0.02-0.1% w / w),
ii. Tazarotene (0.05-0.1% w / w),
iii. Adapalene (0.1-0.3% w / w), and iv. Additional retinoids.
4). Topical antibiotics to kill Acne bacteria directly:
a. Erythromycin (1-3% w / w),
b. Clindamycin (1-2% w / w), and c. Tetracycline (1-3% w / w).

Possible combinations that can be used:
1. Dapsone (0.01% to 10% w / w) + retinoid (0.001% to 3% w / w)
Example:
a. Dapson 5% w / w + adapalene 0.3% w / w,
b. Dapsone 5% w / w + tazarotene 0.1% w / w, and c. Dapson 5% w / w + Tretinoin 0.1% w / w.
2. Dapsone + benzoyl peroxide:
Example:
a. Dapsone 5% w / w + benzoyl peroxide 5% w / w.
3. Dapsone + antibiotics:
Example:
a. Dapson 5% w / w + clindamycin 1% w / w.
4). Examples of dapsone + keratolytic agents:
a. Dapsone 5% w / w + azelaic acid 20% w / w.

  Concentration values in parentheses (w / w) represent preferred concentrations, but other concentration values (w / v) may be used depending on the formulation characteristics and the desired level of efficacy and tolerability .

  A recent clinical experiment evaluated the safety and efficacy of dapsone gel co-administered with adapalene gel. This study design consisted of having the patient apply the product Aczone® (5% w / w Dapsone) twice daily, morning and evening. Approximately 10 minutes after the night application of Aczone®, the patient applied a thin layer of 0.1% w / w adapalene gel. The 10 minute interval between the application of the two products ensures complete absorption of the Aczone® formulation into the skin and minimizes possible negative effects on the skin penetration of adapalene or dapsone Suppressed. Application of 0.1% w / w adapalene gel immediately after the application of Aczone® resulted in a situation where adapalene or dapsone could have had lower skin penetration due to mixing of the two formulation media It may be. Furthermore, the additional thickness of the combined formulation may increase the penetration distance of the two active substances and also lead to a decrease in the skin penetration of the active substances.

  The results of this experiment showed that dapsone gel administered at the same time (but not together) with adapalene gel is safe for the treatment of acne vulgaris and has good solubility resistance. One aspect of the invention is a combined adapalene / Dapson topical formulation that combines two active agents into one formulation. The novelty of the present invention is due, in part, to the use of additional excipients (solubilizing agents) in combination with diethylene glycol monoethyl ether (“DGME”) to solubilize dapsone. The addition of a cosolvent allowed complete dissolution of dapsone in the formulation and increased solubility of adapalene (adapalene is not completely solubilized in these formulations). Increased concentrations of dissolved dapsone and adapalene will increase the skin penetration rate of both drugs into and through the skin, as compared to commercially available comparative products administered simultaneously.

  The topical dosage forms of the present invention include, but are not limited to, solutions, gels, creams, ointments, foams, emulsions, films, and facial / dermabrasion. The present invention is formulated to optimize the transdermal delivery profile of adapalene and dapsone to effectively treat acne and other skin conditions and improve the efficiency of pharmaceutical products applied to the skin Intended for topical dapsone and adapalene formulations.

  Examples of some formulations, excipients, and concentration ranges encompassed by the present invention are summarized in Table 1 below.

  More specific compositions of the present invention of 5% w / w dapsone and 0.1% w / w and 0.3% w / w adapalene formulations include, but are not limited to:

The preparation of the present invention can be prepared as follows based on the excipient.
Process for making lactic acid containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, lactic acid, polyethylene glycol 400 and benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved,
c. Add adapalene to the mixture of step b;
d. While continuing to mix, slowly add hydroxyethylcellulose to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

Process for making DMI / hydroxyethylcellulose containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, dimethylisosorbide, polyethylene glycol 400, benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved.
c. Add adapalene to the mixture of step b;
d. While continuing to mix, slowly add hydroxyethylcellulose to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

Process for making DMI / Carbopol containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, dimethylisosorbide, polyethylene glycol 400, benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved,
c. Add adapalene to the mixture of step b;
d. While mixing continues, slowly add Carbopol 980 to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

Process for making PG / PEG containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, propylene glycol, polyethylene glycol 400, and benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved,
c. Add adapalene to the mixture of step b;
d. While mixing continues, slowly add Carbopol 980 to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

Process for making PG / DMI / Carbopol containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, propylene glycol, dimethyl isosorbide and benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved,
c. Add adapalene to the mixture of step b;
d. While mixing continues, slowly add Carbopol 980 to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

Process for making PG / DMI / HEC containing formulation:
A combined adapalene / Dapson gel was prepared as follows.
a. Measure Transcutol in the kettle. Add dapsone, propylene glycol, dimethyl isosorbide and benzyl alcohol. Stir at room temperature using a propeller mixer. Mix until dissolved,
b. Water, EDTA, and citric acid are added to the mixture of step a. Mix until dissolved,
c. Add adapalene to the mixture of step b;
d. While continuing to mix, slowly add hydroxyethylcellulose to the mixture of step c, avoiding flocculation. Mix vigorously at room temperature until a uniform mass-free dispersion is obtained,
e. Sufficient sodium hydroxide is added with mixing to obtain a pH of 5.3-5.7. Mix until uniform.

  The most effective dapsone and adapalene compositions are selected based on clinical studies. For example, a clinical study consists of one group applying daily selected dapsone and adapalene formulation to the acne site of skin for a period of 12 weeks, and topically applying the same selected dapsone and adapalene formulation twice daily 1 This is done by forming two treatment groups of groups. Two control groups are formed in which a medium consisting of the same excipients but without the active ingredient is applied once and twice daily. The number of inflammatory and non-inflammatory acne lesions in the patient should be recorded at baseline prior to initiation of therapy and at selected intervals throughout the study. Reduction of the total number of non-inflammatory or inflammatory lesions determines the efficacy of the formulation. An established Global Acne Assessment Score (GAAS) should be used to assess product effectiveness. Tolerability of the product can be determined by assessment of skin dryness, irritation, sensitivity, and redness as a result of treatment. A product is considered to be better tolerated if it has little effect on these parameters.

Method of applying:
1. Suitable application methods are topical creams, gels, lotions, ointments, foams, liquids or semi-solid preparations. Topical preparations may contain additional ingredients to provide aesthetic and moisturizing and anti-inflammatory benefits to the skin. generally,
a. The gel or liquid preparation may be alcohol or aqueous based, or a combination of the two,
b. Nanoemulsion or microemulsion preparations can be used to improve the delivery of active agents,
c. Liposomal creams or lotion preparations can be used to improve the delivery of active substances,
d. The foam preparation can be a quick breaking foam containing an additional softener component.
2. Topical preparations that provide sustained or controlled release of the active agent can also be used to provide an optimal balance between efficacy and tolerability.
3. Active ingredients encapsulated in microbeads or adsorbed to microsponges can be used for controlled release, and any incompatibility issues between formulation ingredients can be eliminated.
4). Its application is preferably once a day or more frequently, depending on the desired effect.

Application of the formulation of the present invention:
Example No. 1—Application of 0.1% w / w adapalene of Formula 1 in FIG. 5 A 17 year old Caucasian male patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, FIG. A 0.1% w / w adapalene formulation according to formulation No. 1 is applied. This 17 year old male patient applies the 0.1% w / w adapalene composition of Formula 1 once a day for 12 weeks. After 12 weeks, a 17 year old male patient experiences a 32% reduction in inflammatory and non-inflammatory lesions.

Example No. 2—Application of 0.3% w / w adapalene of Formula 1 in FIG. 5 A 16 year old Caucasian female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, FIG. A 0.3% w / w adapalene formulation according to formulation No. 1 is applied. This 16 year old female patient applies the 0.3% w / w adapalene composition of Formula 1 once a day for 12 weeks. After 12 weeks, a 16 year old female patient experiences a 41% reduction in inflammatory and non-inflammatory lesions.

Example No. 3—Application of 0.1% w / w adapalene of Formula 2 in FIG. 5 A 23 year old African American female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions Then, a 0.1% w / w adapalene formulation according to formulation No. 2 in FIG. 5 is applied. This 23 year old female patient applies the 0.1% w / w adapalene composition of Formula 2 once a day for 12 weeks. After 12 weeks, a 23 year old female patient experiences a 24% reduction in inflammatory and non-inflammatory lesions.

Example No. 4—Application of 0.3% w / w adapalene of Formula 2 in FIG. 5 A 19 year old Caucasian female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, FIG. A 0.3% w / w adapalene formulation according to formulation No. 2 is applied. This 19 year old female patient applies the 0.3% w / w adapalene composition of Formula 2 once a day for 12 weeks. After 12 weeks, this patient experiences a 248% reduction in inflammatory and non-inflammatory lesions.

Example No. 5—Application of 0.1% w / w adapalene of Formula 3 in FIG. 5 An 18 year old African American male patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions The 0.1% w / w adapalene formulation according to formulation number 3 in FIG. 5 is applied. This 18 year old male patient applies 0.1% w / w adapalene composition once a day for 12 weeks. After 12 weeks, an 18 year old male patient experiences a 29% reduction in inflammatory and non-inflammatory lesions.

Example No. 6—Application of 0.3% w / w adapalene of Formula 3 in FIG. 5 A 23 year old Asian female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, A 0.3% w / w adapalene formulation according to formulation number 3 of 5 is applied. This 23 year old patient applies 0.3% w / w adapalene composition once a day for 12 weeks. After 12 weeks, this patient experiences a 25% reduction in inflammatory and non-inflammatory lesions.

Example No. 7—Application of 0.1% w / w adapalene of Formula 4 in FIG. 5 An 18 year old African American male patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions The 0.1% w / w adapalene formulation according to formulation number 3 in FIG. 5 is applied. This 18 year old male patient applies 0.1% w / w adapalene composition once a day for 12 weeks. After 12 weeks, an 18 year old male patient experiences a 29% reduction in inflammatory and non-inflammatory lesions.

Example No. 8—Application of 0.3% w / w adapalene of Formula 4 in FIG. 5 A 17 year old Caucasian female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, FIG. A 0.3% w / w adapalene formulation according to formulation No. 4 is applied. This 17-year-old male patient applies 0.3% w / w adapalene composition twice a day for 12 weeks. After 12 weeks, a 17 year old male patient experiences a 41% reduction in inflammatory and non-inflammatory lesions.

Example No. 9—Application of 0.1% w / w adapalene of Formula 5 of FIG. 5 A 16 year old Caucasian female patient suffers from acne vulgaris with a combination of inflammatory and non-inflammatory lesions, FIG. A 0.1% w / w adapalene formulation according to formulation No. 5 is applied. This 16 year old female patient applies 0.1% w / w adapalene composition once a day for 12 weeks. After 12 weeks, this patient experiences a 27% reduction in inflammatory and non-inflammatory lesions.

Example No. 10—Example No. 9—Application of 0.3% w / w adapalene of Formula 5 in FIG. 5 A 19-year-old Caucasian female patient has acne vulgaris with a combination of inflammatory and non-inflammatory lesions. Apply 0.3% w / w adapalene formulation according to formulation number 5 in FIG. This 19 year old female patient applies 0.3% w / w adapalene composition twice a day for 12 weeks. After 12 weeks, this patient experiences a 38% reduction in inflammatory and non-inflammatory lesions.

Example No. 11—Application of 0.1% w / w adapalene of Formula 1 of FIG. 5 A 37 year old Caucasian male patient suffers from rosacea and has 0.1% w / w of Formula No. 1 of FIG. Apply adapalene formulation. This 37 year old male patient applies the 0.1% w / w adapalene composition of Formula 1 once a day for 12 weeks. After 12 weeks, a 37 year old male patient experiences a reduction in symptoms of rosacea.

Claims (20)

A dermatological composition comprising dapsone, adapalene, and water. The dermatological composition according to claim 1, comprising 5% w / w dapsone and 0.1% w / w adapalene, used for the treatment of acne vulgaris. The dermatological composition according to claim 2, which is 0.5% w / w dapsone and 0.3% w / w adapalene. The dermatological composition according to claim 1, which is a gel. 0.5% w / w dapsone, 0.1% w / w adapalene, 1.5% w / w benzyl alcohol, Transcutol, 5-25% w / w PEG400, 0.01% w / w 2. The composition of claim 1, wherein the composition is EDTA and 0.03% w / w citric acid. 6. The composition of claim 5, further comprising 1-4% w / w hydroxyethylcellulose. 6. The composition of claim 5, further comprising 0.5-2% w / w Carbopol 980. 6. The composition of claim 5, further comprising methyl paraben. The composition of claim 5 further comprising lactic acid. The composition of claim 5 further comprising glycerin. 6. The composition of claim 5, further comprising 5-15% w / w dimethyl isosorbide. 6. A composition according to claim 5, wherein Transcutol is present in an amount of 25% w / w. 6. The composition of claim 5, wherein a buffer selected from the group consisting of NaOH, trolamine, and hydrochloric acid is added to adjust the pH. 14. A composition according to claim 13, wherein the pH of the composition is 5.5. 6. The composition of claim 5, further comprising 2-3% hydroxyethyl cellulose. The composition of claim 1 in a form selected from the group consisting of gels, emulsions, creams, liquids, pastes, lotions, nanoemulsions, microemulsions, inverse emulsions, and liposomal creams. Acne vulgaris, rosacea, atopic dermatitis, treatment of chronic wounds, pressure ulcers, keratosis pilaris, sebaceous cysts, inflammatory skin diseases, post-inflammatory pigmentation, eczema, dryness, pruritus 6. A composition according to claim 5, which can be used for the treatment of one symptom selected from the group consisting of: lichen planus, nodular rash, dermatitis, eczema and rash, and other skin conditions. A method of treating acne vulgaris by application of the composition of claim 1. The treatment method according to claim 17, wherein the application is once a day. The method of treatment according to claim 17, wherein the application is twice a day.

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