CA2223383A1 - Topical vehicles containing solubilized and stabilized azelaic acid - Google Patents
Topical vehicles containing solubilized and stabilized azelaic acid Download PDFInfo
- Publication number
- CA2223383A1 CA2223383A1 CA002223383A CA2223383A CA2223383A1 CA 2223383 A1 CA2223383 A1 CA 2223383A1 CA 002223383 A CA002223383 A CA 002223383A CA 2223383 A CA2223383 A CA 2223383A CA 2223383 A1 CA2223383 A1 CA 2223383A1
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- Prior art keywords
- glycol
- azelaic acid
- composition according
- mixture
- polypropylene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/362—Polycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8158—Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
A completely solubilized topical composition of azelaic acid in a glycol base which is stable at normal temperatures and pressures and which is useful as a commercial substitute for dispersed azelaic acid preparations.
Description
W O 96/39119 PCTrU~9~ S1-~OPICAL VEHICLES CONTAINING SOLUBILIZED
AND STABILIZED A~T.ATC ACID
INTRODUCTION
The present invention relates to topical compositions cont~; n; ng azelaic acid and glycol and more particularly to new and im~lo~d compositions containing stabilized and completely solubilized azelaic acid.
BACKGROUND OF THE lNv~ loN
This invention relates to a completely solubilized and stable topical formulation of azelaic acid at normal temperatures and st~n~d atmospheric pressures. Topical azelaic acid formulations have been used to address a wide range of physiological maladies including acne, hyperpigmentary dermatoses, hair loss, wrinkling, hyperhidrosis, non-acne inflammatory dermatoses, infectious cutaneous diseases and ichthyosis.
However, the only topical formulations of azelaic acid presently known are dispersions. Dispersions deliver azelaic acid in an ~ colved state. When applied to the skin, lln~; ccolved azelaic acid is not readily absorbed and as a result an ~Y~e~ of azelaic acid must be present to be effective. The higher the concentration of azelaic acid, the more likely irritation (burning, stinging and re~n~C) to the skin will occur.
What is needed is a completely solubilized topical azelaic acid composition. Solubilized ~elaic acid is much less likely to irritate the skin because azelaic acid in a dissolved state is much more readily ~bsorbed by the W O 96/39119 PCT/U~3~ 35~5 need be present in the formulation to be effective thereby lowering the risk of irritation to the skin.
While azelaic acid is somewhat soluble in water, cosmetic oils and alcohols, each of these solvents has serious limitations. Thus, water only marginally dissolves azelaic acid so that a water and azelaic acid solution would contain a maximum of about .24~ by weight (w/w) azelaic acid, not likely enough to be effective.
Azelaic acid has little or no solubility in cosmetic oils.
Alcohols are good solvents but are unsatisfactory because large amounts of alcohol e.g., isopropyl alcohol, in a topical composition has the undesirable side effect of drying the skin. Indeed, some alcohols e.g., ethyl alcohol, render azelaic acid unstable at normal temperatures and atmospheric pressures resulting in a totally ineffective composition.
U.S. Patent Nos. 4,292,326 (Nazzaro-Porro, Sep. 29, 1981), 4,386,104 (Nazzaro-Porro, May 31, 1983), and 4,818,768 (Nazzaro-porro, Apr. 4, 1989) all teach dispersions of non-solubilized azelaic acid containing 10%
- 20% (w/w) azelaic acid.
U.S. Patent Nos. 4,713,394 (Thornfeldt, Dec. 15, 1987) and 4,885,282 (Thornfeldt, Dec. 5, 1989) both teach two formulations, A and B, of azelaic acid. Formulation A is an azelaic acid formulation containing a large ~ GpO~; Lion of ethanol. While ethyl alcohol dissolves azelaic acid, it also renders the azelaic acid unstable at normal temperatures and atmospheric pressures meAn i ng a marketable product is not possible. Formulation B teaches a dispersion of azelaic acid.
W O 96/39119 PCT/U','~ S4S
Japan Patent No. 59,020,213 (Shiseido) teaches a hair cosmetic emulsion containing no azelaic acid but a chemical derivative of azelaic acid. The derivative is not completely solubilized but only partially dissolved in a water-glycol base.
A emulsion containing lo - 20~ concentration of azelaic acid in a base of water, apple pectin and sunflower oil was taught by Berova, N., et al. in "Hypoallergic cosmetic Emulsion with Azelaic Acid for Prophylaxy and Treatment of Acne Vulgaris," Berova, N., Nkiolova, A., Krat~h~ov, Chr., and Popova, M., Journal of A~plied CosmetoloqY, vol. 12, no. 3, p. 51 (1994). Berova et al. attribute the mildness of their formulation to the use of natural ingredients like apple pectin and sunflower oil instead of non-natural substances in the azelaic acid vehicle. The emulsion taught by Berova et al. is not completely solubilized and suffers from the same problem as do the Nazzaro-Porro and Thornfeldt formulations, the weight percent of azelaic acid in the formulation is higher than needed because the azelaic acid is not completely solubilized.
The art has yet to find a formulation for completely solubilizing azelaic acid at normal temperatures and atmospheric pressures without sacrificing the stability of the solubilized azelaic acid. Solubilized azelaic acid must remain stable at normal temperatures and atmospheric pressures in order to provide a marketable product.
Without a stable, completely solubilized formula of azelaic acid, the benefits of azelaic acid are unavailable to many users who experience the burning, stinging and r~ Cc of the skin associated with exposure to high CA 02223383 l997-l2-03 W O 96/39119 PCT/U~f~ 515 levels of undissolved azelaic acid in dispersions. The present invention provides a completely solubilized and stable formulation of azelaic acid in a glycol base at normal temperatures and pressures and whose shelf life makes a marketable product possible and reduces the amount of azelaic acid the user must be exposed to in order to enjoy its benefits.
BRIEF SUMMARY OF THE INVENTION
This invention relates to topical compositions of azelaic acid and more specifically to compositions cont~; n; ng stabilized and completely solubilized azelaic acid and glycol that are used to treat a wide variety of skin conditions. The present invention delivers azelaic acid to the skin in a completely solubilized yet stable form thus insuring excellent absorption by the skin and significantly reducing the incidence of skin irritation.
Azelaic acid, a straight chain dicarboxylic acid with 9 carbons, has limited solubility in water and commonly used cosmetic oils. Low levels of azelaic acid (from about 0.5% (w/w) to about 10% (w/w)) may be completely dissolved in glycol (from about 20% (w/w) to about 60%
(w/w)) and remain in stable solution. The glycol utilized may be one or more of the following: propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol, ethoxydiglycol, polypropylene glycol ethers, and hexylene glycol, although other glycols that readily dissolve azelaic acid may also be selected.
W O 96~9119 PCT/U~G~55~5 Accordingly, a primary object of the invention is to provide a stable and completely solu~ilized formulation containing azelaic acid.
Another object is to provide lower, yet effective, concentrations of a topical azelaic acid formulation that is less likely to irritate the skin of the user.
A further object of the invention is to provide a stable, solubilized azelaic acid formulation that can be stored for long periods at normal temperatures and atmospheric pressures.
A still further object is to provide a completely solubilized and stabilized topical formulation containing azelaic acid that addresses a large variety of skin conditions.
These and still further objects as shall hereinafter appear are fulfilled by the present invention in a remarkablyll~eYr~cted fashion as will be readily discerned from a careful consideration of the following detailed description of preferred embodiments thereof especially when read in conjunction with the several examples appended thereto.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention relates to a topical cosmetic preparation containing azelaic acid stabilized and completely solubilized in a glycol base. The preparation is used to treat a wide variety of skin ailments with little or no irritation to the skin. The glycol easily and completely dissolves the azelaic acid without W O 96/39119 PCT/U~,G~S~5 affecting the stability of the azelaic acid. The absence of ethanol or other destabilizing solvents insures the azelaic acid remains stable.
The glycol utilized may be one or more of the following: propylene glycol, polypropylene glycol, polypropylene glycol ethers, hexylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol and ethoxydiglycol, although other glycols that readily dissolve azelaic acid may also be selected. The amount of glycol may vary from about 20%
to 60% (w/w). 20% (w/w) glycol is the minimum amount required to solubilize an effective amount of azelaic acid. 60% (w/w) is probably the maximum level that could be used without completely sacrificing the formulation's aesthetics. Somewhere in the middle of this range is most ideal.
Preferably, a cream or gel topical solution can be made with about 1 - 10% (w/w) of azelaic acid dissolved in about 20 - 60% (w/w) glycol. If lower levels (about 0.5 to about 2.5% (w/w)) of azelaic acid are used, the glycol level can be reduced and conventional emulsions with cosmetic oils formed. With levels of glycol greater than 30% (w/w), emulsion stability is sacrificed. But with glycol levels of about 20% to about 30% (w/w) the stability of emulsions with moisturizing ingredients are acceptable. Moreover, the addition of moisturizing ingredients greatly im~ve the aesthetics of creams and gels.
To further aid in the underst~Aing of the present invention, and not by way of limitation, the following examples are presented:
CA 02223383 l997-l2-03 W O 96/39119 PCT/U~,C.'U~5~5 In one practice of the present invention, and our preferred embodiment thereof, a topical cream is produced by mixing about 20.0 to 60.0% (w/w) of ethoxydiglycol, about 3% (w/w) of diisopropyl adipate and about 1.0 % to 10.0% (w/w) of azelaic acid until a clear solution is formed. In a separate container, q.s. distilled water and about 5.0% (w/w) of PEG-60 almond glycerides are mixed and heated to 70~C. To this mixture, about 8% (w/w) of glycol distearate is added and all three ingredients are mixed while maintaining a temperature of 70~C until the whole forms a white homogeneous fluid. This mixture was allowed to cool to 400C to which the azelaic acid-ethoxydiglycol-diiso~opyl adipate mixture is added. About 2.5% (w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7, (which mixture is available as SEPIGEL 305 from Seppic Department Cosmetique-Pharacie, Paris, France), is then added and the whole was mixed until a thick and homogeneous cream resulted.
A translucent gel can be made from the above formulation by removing the glycol distearate therefrom.
In another preferred practice of the present invention, a topical cream is produced by mixing about 1.0% to 10.0% (w/w) of azelaic acid with about 20.0% to 60.0% (w/w) of dipropylene glycol and heating the mixture to about 60~C until a clear solution is formed. The solution is then cooled to and main~;nP~ at 40~C. In a separate container, about 5.0% (w/w) PEG-60 almond glycerides and q.s. distilled water are mixed and heated W O 96/39119 PCTAJS9GI~554S
to about 70~C. To this mixture, about 8.0% (w/w) of glycol distearate is added and all three ingredients are ;Ye~ while maint~in;ng a temperature of 70~C until the whole forms a white homogeneous fluid. This mixture is then allowed to cool to 40~C and the azelaic acid-dipropylene glycol mixture is added thereto and mixed therein. About 2.0% (w/w) of a mixture of polyacrylamide, C13-Cl4 isoparaffin and Laureth 7 (SEPIGEL 305) is then added and the whole mixed until a thick and homogeneous cream results.
A translucent gel can be made from the above formulation by removing the glycol distearate therefrom.
lS EXAMPLE 3 In yet another practice of the present invention, an emulsion with commonly used cosmetic oils is made by mixing about 0.5% to 2.5% (w/w) of azelaic acid with about 20.0% to 30.0% (w/w) of dipropylene glycol and q.s.
distilled water which mixture is then heated to 70~C until a clear solution results. In a separate container, about 10.0% (w/w) of C12-C15 Alkyl benzoate, about 3.0% (w/w) of isododecane, about 6.0% (w/w) of cyclomethicone, about 2.5% (w/w) of stearyl alcohol, about 4.0% (w/w) of a commercial mixture of glyceryl stearate and PEG-100 stearate, (available as ARLACEL 165 from ICI American Inc., Wilmington, Delaware), and about 0.1% (w/w) of a commercial mixture of isopropylparaben, isobutylparaben and butylparaben, (available as LIQUAPAR OIL from Sutton Laboratories, Chatham, N.J.), were mixed and heated to about 70~C. To this mixture the azelaic acid-dipropylene glycol-water mixture (also at 70~C) is added and the whole mixed while maintaining the temperature at 70~C. The W O 96/39119 PCT/U~3G~'~5'1~
mixture is then allowed to cool to 45~C. Lastly, about 0.8% (w/w) of SEPIGEL 305 is added and the whole mixed until thick and homogeneous.
Each of the products produced by the foregoing Examples, hereinafter designated "Formula 1", "Formula 2"
and "Formula 3", respectively (each Formula number corresponding to the Example by which it was produced, was then tested following the methods outlined in: Grove, G.L., Soschin, A.M. and Kligman, A.M., "Guidelines for Performing Facial Stinging Tests," available from Skin Study Center, Simon Greenburg Foundation, 3901 Market Street, Philadelphia, PA and the Duhring Laboratories, Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, and incorporated herein by this reference thereto.
The effectiveness of Formula 1 was tested on a panel of 17 individuals having r~ iCh or hyperpigmented skin.
The discoloration of the skin was measured using a MINOLTA
CHROMA~ETER Model CR-200. The panelists applied Formula 1 to the discolored skin once per day for 4 weeks. At the end of the 4 week period the skin discoloration was again measured using the MINOLTA ~U~oMAM~TER. Results showed a significant reduction of skin discoloration for the group as an average.
The mildness of Formulae 2 and 3 were tested on a panel of 18 people, some of whom were classified as "stingers." A "stinger" is a person who experiences stinging, burning or itc-h;~g after an application of 5%
lactic acid solution to the naso-labial area of the face.
These "stingers" are considered to have sensitive skin.
W O 96/39119 PCT~US96/~3515 Results of the tests showed that both formulas were considered to be mild using Kligman's scale.
J
From the foregoing, it is apparent that novel and unique topical vehicles containing solubilized and stabilized azelaic acid have been herein described and illustrated which fulfills all of the aforestated objectives in a remarkably unexpected fashion. It is, of course understood that such modifications, variations or adaptations as may readily occur to an artisan familiar with the art to which this invention pertains are intended within the spirit of this invention which is limited only by the scope of the claims appended hereto.
AND STABILIZED A~T.ATC ACID
INTRODUCTION
The present invention relates to topical compositions cont~; n; ng azelaic acid and glycol and more particularly to new and im~lo~d compositions containing stabilized and completely solubilized azelaic acid.
BACKGROUND OF THE lNv~ loN
This invention relates to a completely solubilized and stable topical formulation of azelaic acid at normal temperatures and st~n~d atmospheric pressures. Topical azelaic acid formulations have been used to address a wide range of physiological maladies including acne, hyperpigmentary dermatoses, hair loss, wrinkling, hyperhidrosis, non-acne inflammatory dermatoses, infectious cutaneous diseases and ichthyosis.
However, the only topical formulations of azelaic acid presently known are dispersions. Dispersions deliver azelaic acid in an ~ colved state. When applied to the skin, lln~; ccolved azelaic acid is not readily absorbed and as a result an ~Y~e~ of azelaic acid must be present to be effective. The higher the concentration of azelaic acid, the more likely irritation (burning, stinging and re~n~C) to the skin will occur.
What is needed is a completely solubilized topical azelaic acid composition. Solubilized ~elaic acid is much less likely to irritate the skin because azelaic acid in a dissolved state is much more readily ~bsorbed by the W O 96/39119 PCT/U~3~ 35~5 need be present in the formulation to be effective thereby lowering the risk of irritation to the skin.
While azelaic acid is somewhat soluble in water, cosmetic oils and alcohols, each of these solvents has serious limitations. Thus, water only marginally dissolves azelaic acid so that a water and azelaic acid solution would contain a maximum of about .24~ by weight (w/w) azelaic acid, not likely enough to be effective.
Azelaic acid has little or no solubility in cosmetic oils.
Alcohols are good solvents but are unsatisfactory because large amounts of alcohol e.g., isopropyl alcohol, in a topical composition has the undesirable side effect of drying the skin. Indeed, some alcohols e.g., ethyl alcohol, render azelaic acid unstable at normal temperatures and atmospheric pressures resulting in a totally ineffective composition.
U.S. Patent Nos. 4,292,326 (Nazzaro-Porro, Sep. 29, 1981), 4,386,104 (Nazzaro-Porro, May 31, 1983), and 4,818,768 (Nazzaro-porro, Apr. 4, 1989) all teach dispersions of non-solubilized azelaic acid containing 10%
- 20% (w/w) azelaic acid.
U.S. Patent Nos. 4,713,394 (Thornfeldt, Dec. 15, 1987) and 4,885,282 (Thornfeldt, Dec. 5, 1989) both teach two formulations, A and B, of azelaic acid. Formulation A is an azelaic acid formulation containing a large ~ GpO~; Lion of ethanol. While ethyl alcohol dissolves azelaic acid, it also renders the azelaic acid unstable at normal temperatures and atmospheric pressures meAn i ng a marketable product is not possible. Formulation B teaches a dispersion of azelaic acid.
W O 96/39119 PCT/U','~ S4S
Japan Patent No. 59,020,213 (Shiseido) teaches a hair cosmetic emulsion containing no azelaic acid but a chemical derivative of azelaic acid. The derivative is not completely solubilized but only partially dissolved in a water-glycol base.
A emulsion containing lo - 20~ concentration of azelaic acid in a base of water, apple pectin and sunflower oil was taught by Berova, N., et al. in "Hypoallergic cosmetic Emulsion with Azelaic Acid for Prophylaxy and Treatment of Acne Vulgaris," Berova, N., Nkiolova, A., Krat~h~ov, Chr., and Popova, M., Journal of A~plied CosmetoloqY, vol. 12, no. 3, p. 51 (1994). Berova et al. attribute the mildness of their formulation to the use of natural ingredients like apple pectin and sunflower oil instead of non-natural substances in the azelaic acid vehicle. The emulsion taught by Berova et al. is not completely solubilized and suffers from the same problem as do the Nazzaro-Porro and Thornfeldt formulations, the weight percent of azelaic acid in the formulation is higher than needed because the azelaic acid is not completely solubilized.
The art has yet to find a formulation for completely solubilizing azelaic acid at normal temperatures and atmospheric pressures without sacrificing the stability of the solubilized azelaic acid. Solubilized azelaic acid must remain stable at normal temperatures and atmospheric pressures in order to provide a marketable product.
Without a stable, completely solubilized formula of azelaic acid, the benefits of azelaic acid are unavailable to many users who experience the burning, stinging and r~ Cc of the skin associated with exposure to high CA 02223383 l997-l2-03 W O 96/39119 PCT/U~f~ 515 levels of undissolved azelaic acid in dispersions. The present invention provides a completely solubilized and stable formulation of azelaic acid in a glycol base at normal temperatures and pressures and whose shelf life makes a marketable product possible and reduces the amount of azelaic acid the user must be exposed to in order to enjoy its benefits.
BRIEF SUMMARY OF THE INVENTION
This invention relates to topical compositions of azelaic acid and more specifically to compositions cont~; n; ng stabilized and completely solubilized azelaic acid and glycol that are used to treat a wide variety of skin conditions. The present invention delivers azelaic acid to the skin in a completely solubilized yet stable form thus insuring excellent absorption by the skin and significantly reducing the incidence of skin irritation.
Azelaic acid, a straight chain dicarboxylic acid with 9 carbons, has limited solubility in water and commonly used cosmetic oils. Low levels of azelaic acid (from about 0.5% (w/w) to about 10% (w/w)) may be completely dissolved in glycol (from about 20% (w/w) to about 60%
(w/w)) and remain in stable solution. The glycol utilized may be one or more of the following: propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol, ethoxydiglycol, polypropylene glycol ethers, and hexylene glycol, although other glycols that readily dissolve azelaic acid may also be selected.
W O 96~9119 PCT/U~G~55~5 Accordingly, a primary object of the invention is to provide a stable and completely solu~ilized formulation containing azelaic acid.
Another object is to provide lower, yet effective, concentrations of a topical azelaic acid formulation that is less likely to irritate the skin of the user.
A further object of the invention is to provide a stable, solubilized azelaic acid formulation that can be stored for long periods at normal temperatures and atmospheric pressures.
A still further object is to provide a completely solubilized and stabilized topical formulation containing azelaic acid that addresses a large variety of skin conditions.
These and still further objects as shall hereinafter appear are fulfilled by the present invention in a remarkablyll~eYr~cted fashion as will be readily discerned from a careful consideration of the following detailed description of preferred embodiments thereof especially when read in conjunction with the several examples appended thereto.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention relates to a topical cosmetic preparation containing azelaic acid stabilized and completely solubilized in a glycol base. The preparation is used to treat a wide variety of skin ailments with little or no irritation to the skin. The glycol easily and completely dissolves the azelaic acid without W O 96/39119 PCT/U~,G~S~5 affecting the stability of the azelaic acid. The absence of ethanol or other destabilizing solvents insures the azelaic acid remains stable.
The glycol utilized may be one or more of the following: propylene glycol, polypropylene glycol, polypropylene glycol ethers, hexylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol and ethoxydiglycol, although other glycols that readily dissolve azelaic acid may also be selected. The amount of glycol may vary from about 20%
to 60% (w/w). 20% (w/w) glycol is the minimum amount required to solubilize an effective amount of azelaic acid. 60% (w/w) is probably the maximum level that could be used without completely sacrificing the formulation's aesthetics. Somewhere in the middle of this range is most ideal.
Preferably, a cream or gel topical solution can be made with about 1 - 10% (w/w) of azelaic acid dissolved in about 20 - 60% (w/w) glycol. If lower levels (about 0.5 to about 2.5% (w/w)) of azelaic acid are used, the glycol level can be reduced and conventional emulsions with cosmetic oils formed. With levels of glycol greater than 30% (w/w), emulsion stability is sacrificed. But with glycol levels of about 20% to about 30% (w/w) the stability of emulsions with moisturizing ingredients are acceptable. Moreover, the addition of moisturizing ingredients greatly im~ve the aesthetics of creams and gels.
To further aid in the underst~Aing of the present invention, and not by way of limitation, the following examples are presented:
CA 02223383 l997-l2-03 W O 96/39119 PCT/U~,C.'U~5~5 In one practice of the present invention, and our preferred embodiment thereof, a topical cream is produced by mixing about 20.0 to 60.0% (w/w) of ethoxydiglycol, about 3% (w/w) of diisopropyl adipate and about 1.0 % to 10.0% (w/w) of azelaic acid until a clear solution is formed. In a separate container, q.s. distilled water and about 5.0% (w/w) of PEG-60 almond glycerides are mixed and heated to 70~C. To this mixture, about 8% (w/w) of glycol distearate is added and all three ingredients are mixed while maintaining a temperature of 70~C until the whole forms a white homogeneous fluid. This mixture was allowed to cool to 400C to which the azelaic acid-ethoxydiglycol-diiso~opyl adipate mixture is added. About 2.5% (w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7, (which mixture is available as SEPIGEL 305 from Seppic Department Cosmetique-Pharacie, Paris, France), is then added and the whole was mixed until a thick and homogeneous cream resulted.
A translucent gel can be made from the above formulation by removing the glycol distearate therefrom.
In another preferred practice of the present invention, a topical cream is produced by mixing about 1.0% to 10.0% (w/w) of azelaic acid with about 20.0% to 60.0% (w/w) of dipropylene glycol and heating the mixture to about 60~C until a clear solution is formed. The solution is then cooled to and main~;nP~ at 40~C. In a separate container, about 5.0% (w/w) PEG-60 almond glycerides and q.s. distilled water are mixed and heated W O 96/39119 PCTAJS9GI~554S
to about 70~C. To this mixture, about 8.0% (w/w) of glycol distearate is added and all three ingredients are ;Ye~ while maint~in;ng a temperature of 70~C until the whole forms a white homogeneous fluid. This mixture is then allowed to cool to 40~C and the azelaic acid-dipropylene glycol mixture is added thereto and mixed therein. About 2.0% (w/w) of a mixture of polyacrylamide, C13-Cl4 isoparaffin and Laureth 7 (SEPIGEL 305) is then added and the whole mixed until a thick and homogeneous cream results.
A translucent gel can be made from the above formulation by removing the glycol distearate therefrom.
lS EXAMPLE 3 In yet another practice of the present invention, an emulsion with commonly used cosmetic oils is made by mixing about 0.5% to 2.5% (w/w) of azelaic acid with about 20.0% to 30.0% (w/w) of dipropylene glycol and q.s.
distilled water which mixture is then heated to 70~C until a clear solution results. In a separate container, about 10.0% (w/w) of C12-C15 Alkyl benzoate, about 3.0% (w/w) of isododecane, about 6.0% (w/w) of cyclomethicone, about 2.5% (w/w) of stearyl alcohol, about 4.0% (w/w) of a commercial mixture of glyceryl stearate and PEG-100 stearate, (available as ARLACEL 165 from ICI American Inc., Wilmington, Delaware), and about 0.1% (w/w) of a commercial mixture of isopropylparaben, isobutylparaben and butylparaben, (available as LIQUAPAR OIL from Sutton Laboratories, Chatham, N.J.), were mixed and heated to about 70~C. To this mixture the azelaic acid-dipropylene glycol-water mixture (also at 70~C) is added and the whole mixed while maintaining the temperature at 70~C. The W O 96/39119 PCT/U~3G~'~5'1~
mixture is then allowed to cool to 45~C. Lastly, about 0.8% (w/w) of SEPIGEL 305 is added and the whole mixed until thick and homogeneous.
Each of the products produced by the foregoing Examples, hereinafter designated "Formula 1", "Formula 2"
and "Formula 3", respectively (each Formula number corresponding to the Example by which it was produced, was then tested following the methods outlined in: Grove, G.L., Soschin, A.M. and Kligman, A.M., "Guidelines for Performing Facial Stinging Tests," available from Skin Study Center, Simon Greenburg Foundation, 3901 Market Street, Philadelphia, PA and the Duhring Laboratories, Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, and incorporated herein by this reference thereto.
The effectiveness of Formula 1 was tested on a panel of 17 individuals having r~ iCh or hyperpigmented skin.
The discoloration of the skin was measured using a MINOLTA
CHROMA~ETER Model CR-200. The panelists applied Formula 1 to the discolored skin once per day for 4 weeks. At the end of the 4 week period the skin discoloration was again measured using the MINOLTA ~U~oMAM~TER. Results showed a significant reduction of skin discoloration for the group as an average.
The mildness of Formulae 2 and 3 were tested on a panel of 18 people, some of whom were classified as "stingers." A "stinger" is a person who experiences stinging, burning or itc-h;~g after an application of 5%
lactic acid solution to the naso-labial area of the face.
These "stingers" are considered to have sensitive skin.
W O 96/39119 PCT~US96/~3515 Results of the tests showed that both formulas were considered to be mild using Kligman's scale.
J
From the foregoing, it is apparent that novel and unique topical vehicles containing solubilized and stabilized azelaic acid have been herein described and illustrated which fulfills all of the aforestated objectives in a remarkably unexpected fashion. It is, of course understood that such modifications, variations or adaptations as may readily occur to an artisan familiar with the art to which this invention pertains are intended within the spirit of this invention which is limited only by the scope of the claims appended hereto.
Claims (14)
1. A topical composition comprising azelaic acid completely solubilized in a glycol wherein said solubilized azelaic acid is stable at normal temperatures and standard atmospheric pressures.
2. The composition according to claim 1 wherein said glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxy polyethylene glycol, polypropylene glycol ethers, hexylene glycol, and ethoxydiglycol.
3. The composition according to claim 1 comprising from about 0.5% to about 10% (w/w) of said azelaic acid.
4. The composition according to claim 3 comprising from about 20.0% to about 60.0% (w/w) of said glycol.
5. The composition according to claim 4 wherein said glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxy polyethylene glycol, polypropylene glycol ethers, hexylene glycol, and ethoxydiglycol.
6. The composition according to claim 1 comprising from about 0.5% to about 2.5% (w/w) of said azelaic acid.
7. The composition according to claim 6 comprising from about 20% to about 30% (w/w) of said glycol.
8. The composition according to claim 7 wherein said glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxy polyethylene glycol, polypropylene glycol ethers, hexylene glycol, and ethoxydiglycol.
9. The composition according to claim 6 further comprising about 20.0% to about 30% (w/w) of dipropylene glycol, about 10.0% (w/w) of C12-15 alkyl benzoate, about 3.0% (w/w) of isododecane, about 6.0% (w/w) of cyclomethicone, about 2.5% (w/w) of stearyl alcohol, about 4.0% (w/w) of a mixture of glyceryl stearate and PEG-stearate, about 0.1% (w/w) of a mixture of isopropyl paraben, isobutyl paraben and butyl paraben, about 0.8%
(w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7 and q.s. distilled water.
(w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7 and q.s. distilled water.
10. The composition according to claim 1 comprising from about 1% to about 10 % (w/w) of said azelaic acid.
11. The composition according to claim 10 comprising about 20.0% to about 60% (w/w) of said glycol.
12. The composition according to claim 11 wherein said glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxy polyethylene glycol, polypropylene glycol ethers, hexylene glycol, and ethoxydiglycol.
13. The composition according to claim 10 further comprising about 20% to about 60% ethoxydiglycol, about 3.0% (w/w) of diisopropyl adipate, about 5.0% (w/w) of PEG-60 almond glycerides, about 8.0% (w/w) of glycol distearate, about 2.5% (w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7 and q.s.
distilled water.
distilled water.
14. The composition according to claim 10 further comprising about 20 % to about 60% (w/w) dipropylene glycol, about 5.0% (w/w) of PEG-60 almond glycerides, about 8.0% (w/w) of glycol distearate, about 2.0% (w/w) of a mixture of polyacrylamide, C13-C14 isoparaffin and Laureth 7 and q.s. distilled water.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46947495A | 1995-06-06 | 1995-06-06 | |
| US08/469,474 | 1995-06-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2223383A1 true CA2223383A1 (en) | 1996-12-12 |
Family
ID=23863937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002223383A Abandoned CA2223383A1 (en) | 1995-06-06 | 1996-06-05 | Topical vehicles containing solubilized and stabilized azelaic acid |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5925679A (en) |
| EP (1) | EP0831768A1 (en) |
| JP (1) | JPH11507350A (en) |
| KR (1) | KR19990022343A (en) |
| CN (1) | CN1192134A (en) |
| AU (1) | AU708824B2 (en) |
| BR (1) | BR9608989A (en) |
| CA (1) | CA2223383A1 (en) |
| CO (1) | CO4700435A1 (en) |
| CZ (1) | CZ387097A3 (en) |
| MA (1) | MA23889A1 (en) |
| NZ (1) | NZ309677A (en) |
| PL (1) | PL323716A1 (en) |
| TN (1) | TNSN96082A1 (en) |
| UY (1) | UY24246A1 (en) |
| WO (1) | WO1996039119A1 (en) |
| ZA (1) | ZA964688B (en) |
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| DE10226201A1 (en) * | 2002-06-12 | 2003-12-24 | Ifac Gmbh & Co Kg Inst Fuer An | Ether alcohols as solvents and emulsions and dispersions containing them |
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| US8795693B2 (en) | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
| GB0425945D0 (en) * | 2004-11-26 | 2004-12-29 | Unilever Plc | Underarm cosmetic method and compositions |
| US20080260655A1 (en) | 2006-11-14 | 2008-10-23 | Dov Tamarkin | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
| US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
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| FR2939039B1 (en) * | 2008-12-01 | 2010-12-31 | Basf Beauty Care Solutions France Sas | NEW SEBUM SECRET INHIBITOR AGENT |
| WO2010125470A2 (en) | 2009-04-28 | 2010-11-04 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
| CA2769625C (en) | 2009-07-29 | 2017-04-11 | Foamix Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
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| US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
| CA2776474C (en) | 2009-10-02 | 2021-01-12 | Foamix Ltd. | Topical tetracycline compositions |
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| JP5951277B2 (en) * | 2012-02-17 | 2016-07-13 | ロート製薬株式会社 | External composition containing azelaic acid |
| ITMI20130354A1 (en) * | 2013-03-08 | 2014-09-09 | Again Life Italia Srl | MIXTURE OF FATTY ACIDS (F.A.G. FATTY ACIDS GROUP) FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES. |
| KR101633539B1 (en) * | 2013-12-31 | 2016-06-24 | 동의대학교 산학협력단 | Functional Cosmetic Composition Comprising Azelaic Acid |
| KR101593539B1 (en) * | 2015-07-03 | 2016-02-15 | 고려대학교 산학협력단 | Composition of Azelaic Acid Having Adipose Triglyceride Hydrolysis effect |
| MX2020012139A (en) | 2016-09-08 | 2021-01-29 | Vyne Pharmaceuticals Inc | Compositions and methods for treating rosacea and acne. |
| US11931330B2 (en) | 2018-02-20 | 2024-03-19 | Korea University Research And Business Foundation | Composition for promoting skeletal muscle activity via induction of mitochondrial biogenesis comprising of azelaic acid as an active ingredient |
| US10786475B2 (en) | 2018-02-20 | 2020-09-29 | Korea University Research And Business Foundation | Method for preventing, treating, or improving fatty liver by administering effective amounts of azelaic acid to a subject |
| CN110669226A (en) * | 2019-09-27 | 2020-01-10 | 上海应用技术大学 | Preparation method of azelaic acid supermolecule |
| WO2021212080A1 (en) * | 2020-04-16 | 2021-10-21 | Baek Clinical Inc. | Anhydrous azelaic acid topical formulations |
| BR112022020994A2 (en) * | 2020-04-16 | 2022-12-06 | Baek Clinical Inc | NON-AQUEOUS TOPICAL FORMULATIONS |
| CN113520890B (en) * | 2021-06-29 | 2023-02-17 | 上海瑞叶生物科技有限公司 | Azelaic acid dispersion and preparation method and application thereof |
| CN114869795B (en) * | 2022-03-29 | 2024-01-26 | 上海肤徕生物高科技有限公司 | Preparation method of whitening composition, product and application thereof |
| CN115252449A (en) * | 2022-08-17 | 2022-11-01 | 上海臻臣化妆品有限公司 | Azelaic acid aqueous solution, preparation method thereof and cosmetic composition |
| CN115590777B (en) * | 2022-11-14 | 2023-06-16 | 高宝化妆品（中国）有限公司 | Azelaic acid compound and preparation and application thereof |
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| US4386104A (en) * | 1977-04-19 | 1983-05-31 | Nazzaro Porro Marcella | Process for the treatment of acne |
| IT1114950B (en) * | 1977-12-30 | 1986-02-03 | Porro Marcella | COMPOSITIONS FOR ACNE TREATMENT AND THERAPY |
| JPS5920213A (en) * | 1982-07-27 | 1984-02-01 | Shiseido Co Ltd | Oil-in-water type emulsion for hair cosmetic |
| US4713394A (en) * | 1986-01-17 | 1987-12-15 | Thornfeldt Carl R | Treatment of nonacne inflammatory and infectious dermatoses and hair loss |
| US4885282A (en) * | 1987-07-02 | 1989-12-05 | Thornfeldt Carl R | Treatment of hyperhidrosis, ichthyosis and wrinkling |
| GB9316323D0 (en) * | 1993-08-06 | 1993-09-22 | Procter & Gamble | Cosmetic compositions |
| GB2283421B (en) * | 1993-11-04 | 1997-11-26 | Procter & Gamble | Anti-acne compositions |
| US5549888A (en) * | 1994-01-31 | 1996-08-27 | Procter & Gamble | Aqueous topical anti-acne compositions of low pH |
| CN1145582A (en) * | 1994-03-11 | 1997-03-19 | 普罗克特和甘保尔公司 | Low pH, hydrolytically stable, cosmetic compsn. containing acidic actives |
-
1996
- 1996-05-31 UY UY24246A patent/UY24246A1/en unknown
- 1996-06-04 CO CO96028804A patent/CO4700435A1/en unknown
- 1996-06-05 CN CN96195897A patent/CN1192134A/en active Pending
- 1996-06-05 AU AU59903/96A patent/AU708824B2/en not_active Ceased
- 1996-06-05 ZA ZA9604688A patent/ZA964688B/en unknown
- 1996-06-05 WO PCT/US1996/009545 patent/WO1996039119A1/en active Search and Examination
- 1996-06-05 PL PL96323716A patent/PL323716A1/en unknown
- 1996-06-05 CA CA002223383A patent/CA2223383A1/en not_active Abandoned
- 1996-06-05 KR KR1019970708823A patent/KR19990022343A/en not_active Application Discontinuation
- 1996-06-05 NZ NZ309677A patent/NZ309677A/en unknown
- 1996-06-05 CZ CZ973870A patent/CZ387097A3/en unknown
- 1996-06-05 MA MA24259A patent/MA23889A1/en unknown
- 1996-06-05 TN TNTNSN96082A patent/TNSN96082A1/en unknown
- 1996-06-05 JP JP9501844A patent/JPH11507350A/en active Pending
- 1996-06-05 BR BR9608989A patent/BR9608989A/en not_active IP Right Cessation
- 1996-06-05 EP EP96917267A patent/EP0831768A1/en not_active Withdrawn
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1997
- 1997-09-12 US US08/928,704 patent/US5925679A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| UY24246A1 (en) | 1996-06-14 |
| CZ387097A3 (en) | 1998-06-17 |
| JPH11507350A (en) | 1999-06-29 |
| WO1996039119A1 (en) | 1996-12-12 |
| ZA964688B (en) | 1997-12-05 |
| KR19990022343A (en) | 1999-03-25 |
| US5925679A (en) | 1999-07-20 |
| TNSN96082A1 (en) | 1998-12-31 |
| AU5990396A (en) | 1996-12-24 |
| NZ309677A (en) | 1999-10-28 |
| AU708824B2 (en) | 1999-08-12 |
| CO4700435A1 (en) | 1998-12-29 |
| EP0831768A1 (en) | 1998-04-01 |
| BR9608989A (en) | 1999-06-29 |
| CN1192134A (en) | 1998-09-02 |
| MA23889A1 (en) | 1996-12-31 |
| PL323716A1 (en) | 1998-04-14 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |