MXPA97009892A - Topical vehicles containing solubilized azelaic acid and stabilizer - Google Patents

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 preparations of azelaic acid.

Description

TOPICAL VEHICLES CONTAINING SOLUBILIZED AND STABILIZED FLZELNIC ACID INTRODUCTION The present invention relates to topical compositions containing azelaic acid and glycol and, more particularly, to new and improved compositions which con tain stabilized azelaic acid and completely soluble L Listed.

BACKGROUND OF THE INVENTION This invention relates to a completely solubilized and stable topical formulation of azelaic acid, at normal temperatures and natural atmospheric pressures. Topical formulations of azelaic acid have been used to cope with a wide variety of physiological diseases, including acne, hyperpigrnentaneous dermatoses, hair loss, wrinkles, hyperhidrosis, non-acne dermatoses in the skin. , infectious skin diseases and ichthyosis. However, the only topical formulations of azelaic acid currently known are the dispersions. The dispersions supply azelaic acid in an undissolved state.

When applied to the skin, the undissolved azelaic acid is not easily absorbed and, as a result, an excess of azelaic acid must be present that is effective. Higher concentration of azelaic acid, more likely to occur skin irritation (burning, itching and redness). What is needed is a unique composition of azelaic acid, completely sunburned. The solubilized azelaic acid is much less susceptible to irritate the skin, because the azelaic acid in dissolved ossicle is absorbed much more easily by the p, so it needs to be present in the formulation in smaller quantities to be effective. , decreasing in that way or irritating the skin. Although azeic acid is somewhat soluble in water, in cosmetic oils and in alcohols, each of these solvents has serious limitations. In that way, water only dissolves azelaic acid marginally, so that a solution of water and azelaic acid would contain a maximum of about 0.24% by weight (eg o / o) of azelaic acid, probably not enough for was effective. HZl azelai acid co has little or no solubility in cosmetic oils. Alcohols are good solvents but are not satisfactory because large amounts of alcohol, for example, soproilic alcohol, in a topical composition, have the undesirable side effect of drying the skin. In fact, some alcohols, for example, ethyl alcohol, render azelaic acid unstable at normal temperatures and atmospheric pressures, which results in a totally ineffective composition. U.S. Patent Nos. 4,292,326 (Nazzaro-Porro, September 29, 1981), 4,386,104 (Nazzaro-Porro, May 31, 1983) and 4,818,768 (Nazzaro-Porro, April 4, 1989), teach dispersions of non-azelaic acid. solubilized containing from 10% to 20% (w / w) of azelaic acid co. U.S. Patent Nos. 4, 713, 394 (Thornfeldt, December 15, 1987) and 4,885,282 (Thornfeldt, December 5, 1989) teach both formulations, fi and B, of azelaic acid. The formulation fi is a formulation of azeic acid that contains a large proportion of ethanol. Although ethyl alcohol dissolves azelaic acid, it also makes azelaic acid unstable at normal temperatures and atmospheric pressures, which means that a commercial product is not possible. Formulation B teaches a dispersion of azelaic acid. Japanese Patent No. 59,020,213 (Shisei o) teaches a cosmetic emulsion for hair that does not contain azelaic acid, but a chemical derivative of azelaic acid. The derivative is not completely solubilized, but only partially dissolved in a water-gilcol base. An emulsion containing 10 to 20% concentration of azelaic acid in a water base, apple peel and sunflower oil, was taught by Berova N. and co-authors, in Hypoal lergic Cosrnetic Emulsion ith fizelaic ficid for Prophylaxy and Treatment of ficne Vulgaris, Berova, N. N iolova, fl. Kratchanov, Chr., And Popova M., Journal of Applied Cosmetology, lathe 12, No. 3, page 51 (1994). Berova and coauthors attribute the moderation of their formulation to the use of natural ingredients, such as apple pectin and sunflower oil, instead of unnatural substances, in the vehicle for azelaic acid. The emulsion taught by Berova and coauthors is not completely solubilized and suffers from the same problem as the formulations of Nazzaro-Porro and Thornfeldt: the percentage by weight of azelaic acid in the formulation is higher than necessary, because the azelaic acid It is not completely soluble. the technique has not yet found a formulation to fully solubilize azelaic acid at normal temperatures and atmospheric pressures, without sacrificing the stability of azelac acid solubilized. The solubilized azelaic acid must remain stable at normal temperatures and atmospheric pressures, in order to provide an alkalizable product. Without a stable, fully solubilized formula of azelaic acid, the benefits of azelaic acid are not available to many users, who experience skin burns, flushing and redness associated with exposure to high levels of undissolved azelaic acid in the skin. dispersions. The present invention provides a fully solubilized and stable formulation of azelaic acid in a glycol base, at normal temperatures and pressures, and whose shelf life makes it a possible marketable product, and reduces the amount of azelaic acid to which it must be exposed the user, in order to enjoy its benefits.

BRIEF DESCRIPTION OF THE INVENTION This invention relates to topical compositions of azelaic acid and, more specifically, to compositions containing stabilized and fully solubilized azelaic acid, and glycol; which are used to treat a wide variety of skin conditions. The present invention provides azelaic acid to the skin, in a completely solubilized but stable form, thereby ensuring excellent absorption by the skin and significantly reducing the incidence of skin irritation. Azelaic acid, a straight chain dicarboxylic acid with 9 carbon atoms, has limited solubility in water and commonly used cosmetic oils. It can dissolve low levels of azelaic acid (from about 0.5% (w / w) to about 10% (w / w) in glycol (from about 20% (w / w) to about 60% (in weight / weight), and remain in stable solution The glycol used may be one or more of the following: propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, inet oxy polyethylene glycol, ethylene glycol, polypropylene glycol ethers It is also possible to select other glycols that easily dissolve the azelaic acid, Therefore, it is a primary objective of the invention to provide a stable and completely solubilized formulation containing azelaic acid. but effective, a simple formulation of azelaic acid, which is less likely to irritate the user's skin.Another objective of the invention is to provide a stable formulation of soluble azelaic acid 1 iza It can be stored for long periods at normal temperatures and atmospheric pressures. It is also an objective to provide a completely solubilized and stabilized topical formulation containing azelaic acid, which solves a wide variety of skin conditions. These and other additional objectives that will appear later on are satisfied by the present invention in a remarkably unexpected manner, such that it is easily understood from a careful consideration of the following detailed description of its modalities, especially how much is read. together with the various examples annexed to the present.

DESCRIPTION OF THE PREFERRED MODALITY The present invention relates to a cosmetic preparation containing azelaic acid stabilized and completely solubilized in a glycol base. The preparation is used to treat a wide variety of skin conditions, with little or no skin irritation. The glycol easily and completely dissolves the azelaic acid without affecting the stability of the azelaic acid. The absence of ethanol or other destabilizing solvents ensures that stable azelaic acid perrnanocera. The glycol used can be one or more of the following. propylene glycol, polypropylene glycol, polyether glycol ethers, hei lengli col, Dipropyl, butylene glycol, polyethylene glycol, methoxy polyethylene glycol and ethoxydiglycol, although other glycols can be selected that easily dissolve azelaic acid. The amount of glycol can vary from 20% to 60% (weight / weight), approximately. The minimum amount of glycol is 20% (w / w) to solubilize an effective amount of azelaic acid. Probably the maximum level that could be used is 60% (in weight / weight), without completely sacrificing the aesthetics of the formulation. At some point in the middle of this scale would be ideal. Preferably, a topical solution in cream or gel with about 1-10% (w / w) of free azelacid acid in about 20-60% (w / w) glycol can be made. If lower levels (around 0.5 to 2.5% (w / w)) of azelaic acid are used, the glycol level can be reduced and conventional emulsions can be formed with cosmetic oils. With glycol levels of more than 30% (in weight / weight), the stability of the emulsion is sacrificed. But with glycol levels of around 20% to around 30% (by weight / weight) the stability of the emulsions with wetting ingredients is acceptable. In addition, the addition of moisturizing ingredients improves the aesthetics of the creams and gels. To help better understand the present invention, and in no way as a limitation, the following examples are given: EXAMPLE 1 In a practice of the present invention, and our preferred embodiment, a topical cream is produced by mixing around 20.0 to 60. B; (weight / weight) of ethylene glycol, about 3% (by weight / weight) of diisopropyl adipate and about 1.0% to 10.0% (by weight / weight) of azelaic acid, until a clear solution. In a separate vessel, a sufficient quantity of distilled water is mixed and about 5.0% (w / w) of PEG-60, almond cerils, and heated to 70 ° C. About 8% (w / w) of glycol distearate is added to that mixture and the three ingredients are mixed, while maintaining a temperature of 70 ° C until the total forms a white, homogeneous fluid. This mixture is allowed to cool to 40 ° C, at which temperature the mixture of azelaic acid-oxidi-glycol-dusopro-pyl adipate is added. Then approximately 2.5% (by weight / weight) of a mixture of polyacrylamide, isoparaffin of 13 to 14 carbon atoms and Laureth 7 (mixture obtainable as SEPIGEL 305 from Seppic Department Cosrnetique-Pharrnacie, Paris, France) is added. , and the total is mixed until a thick and homogeneous cream is obtained as a result. A translucent gel of the above formulation can be formed by removing the glycol distearate therefrom.

EXAMPLE 2 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 di-propylene glycol , and heating the mixture to around 60 ° C until a clear solution forms. The solution is then cooled to 40 ° C and maintained at that temperature. In a separate vessel about 5.0% (w / w) of PEG-60, almond glycerides and sufficient amount of water are mixed and heated to about 70 ° C. About 8.0% (w / w) of glycol distearate is added to that mixture, and the three ingredients are mixed while maintaining a temperature of 7 ° C until the total forms a white, homogeneous fluid. Then let this mixture cool to 40oC and add the mixture of azelaic acid-dipropy lengLicol, and mix with it. Then add about 2.0% (w / w) of a mixture of polyacrylamide, isoparaphine of 13 to 14 carbon atoms and Laureth 7 (SEPTGFL 305) and mix the total until it is obtained. result a thick and homogeneous cream. A translucent gel can be formed from the above formulation by removing glycol distearate therefrom.

EXAMPLE 3 In another practice of the present invention an emulsion is made with commonly used cosmetic oils, 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 sufficient amount of water; and said mixture is heated to 70 ° O until a clear solution is obtained as a result. In a separate vessel about 10.0% (w / w) of alkyl benzoate of 12 to 15 carbon atoms, about 3.0% (w / w) of isododecane, about 6.0% ( in weight / weight) of the clomethicone, about 2.5% (w / w) of stearic alcohol, about 4.0% (w / w) of a commercial mixture of glyceryl stearate and PEG-100 stearate (obtain Lble as ARLfiCEL 165 Ie TCI Rrnepcan Tnc, Uilrnington, Del.) and about 0.1% (w / w) of a commercial mixture of isopropilparaben, isobutylparaben and butylparaben (obtainable as LIQURPRR OIL, from Sutton Laboratories, Chatharn, N .3.)) And heated to around- 70 ° C. To this mixture was added the azelaic-dipropyl alcohol-water mixture (also at 70 ° C, and the total was mixed while maintaining the temperature at 70 ° C. Then the mixture was allowed to cool to 45 ° C. about 0.8% (weight / weight) of SEPIGEL 305 is added and the total is mixed until it is thick and homogeneous Each of the products produced by the previous examples, hereinafter referred to as "formula 1", "formula 2" and "formula 3", respectively (each number of formula corresponds to the example by which it was produced) was then tested following the methods outlined in: Grove, GL, Soschin, RM and Kligman, fi. M., Gu delmes for Perforrning Facial Stingmg Tests, available from the Skin Study Center, Simon Greeburg Foundation, 3901 Marl-et Street, Philadelphia, Pfl and Duhpng Laboratories, Department of Dermatology, University of Pennsylvama School of Medicine, Philadelphia, Pfl , 19104, and incorporated herein by this reference to him. The effectiveness of formula 1 was tested in a panel of 17 individuals who had reddish or hyperpigmented skin. The discoloration of the skin was measured using a MTNOLTfi CHROMfiMETER model CR-200. Members of the panel applied formula 1 to discolored skin once a day for 4 weeks. At the end of the 4-week period, skin discoloration was again measured using the MINOLTA CHROMRMETER. The results showed a significant reduction of skin discoloration for the group, on average. The benignity of formulas 2 and 3 was tested on a panel of 18 people, some of whom were classified as "scrapers". A "scraper" is a person who experiences itching, burning or itching after the application of a 5% solution of lactic acid to the nasolabial area of the face. These "scrapers" are considered to be sensitive skin. The results of the tests showed that both formulas were considered benign using the Kligrnan scale. It will be apparent from the foregoing that novel and unique topical vehicles, containing solubilized and stabilized azelaic acid, satisfying all the above-mentioned objects, have been described and illustrated here in a remarkably unexpected manner. Of course, it should be understood that those modifications, variations or adaptations that can easily occur to experts familiar with the technique to which the invention pertains, are intended to be within the spirit of the invention, which is limited only for the scope of the claims that follow.

Claims (14)

NOVELTY OF THE INVENTION CLAIMS

1. - A topical composition, characterized in that it comprises azelaic acid completely solubilized in a glycol, in which the solubilized azelaic acid is stable at normal temperatures and at normal atmospheric pressures.

2. The composition according to claim 1, further characterized in that the glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol, polypropylene glycol ethers, hexylene glycol and ethoxydiglycol.

3. The composition according to claim 1, further characterized in that it comprises about 0.5% to 10% (weight / weight) of azelaic acid.

4. The composition according to claim 3, further characterized in that it comprises from 20.0% to 60.0% (weight / weight) of the glycol.

5. The composition according to claim 4, further characterized in that the glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, methoxypolyethylene glycol, polypropylene glycol ethers, hexylene glycol and ethoxydiglycol.

6. The composition according to claim 1, characterized in that it comprises from about 5% to about 2.5% (by weight / weight) of said azeic acid.

7. - The composition according to claim 6, further characterized in that it comprises from about 20% to about 30% (weight / weight) of said glycol.

8. The composition according to claim 7, further characterized because the glycol of the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, rnetoxipolyethylene glycol, polypropylene glycol ethers, hexagon is selected. lengli cabbage and idiglicol eto.

9. The composition according to claim 6, further characterized in that it additionally comprises about 20.0% to 30% (weight / weight) of dipropylene glycol, about 10.0% (w / w) of benzoate. of alkyl of 12 to 15 carbon atoms; about 3.0% (weight / weight) of isododecane; about 6.0% (w / w) of ethylene cylindrone, about 2.5% (by weight /? that of stearic alcohol; about 4.0% (w / w) of a mixture of glyceryl stearate and stear PEG -ate, about 0.1% (by weight / weight) of a mixture of isopropylparaben, isobutylparaben and butii-paraben, about 0.8% (w / w) of a polyacrylamide mixture, isoparana of 13-14 atoms of car-bond and Laureth 7, and sufficient quantity of distilled water.

10. - The composition according to claim 1, further characterized in that it comprises from 1% to 10% (weight / weight) of the azelaic acid.

11. The composition according to claim 10, further characterized because it comprises approximately 20.0% at about 60% (weight / weight) of the glycol.

12. The composition according to claim 11, further characterized in that the glycol is selected from the group consisting of propylene glycol, polypropylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol, rnetoxipolyethylene glycol, polypropylene glycol ethers, hexylene glycol and ethoxydiglycol.

13. The composition according to claim 10, further characterized in that it additionally comprises about 20% to 60% of ethoxydiglycol, about 3.0% (by weight / weight) of diisopropyl adipate; around 5.0% (w / w) almond glycerides PEG-60; about 8.0% (w / w) of glycol distearate, - about 2.5% (w / w) of a polyacrylamide mixture; isoparaffin of 13-14 carbon atoms and Laureth 7; and sufficient quantity of distilled water.

14. The composition according to claim 10, further characterized in that it additionally comprises about 20% to 60% (w / w) of dipropylene glycol, about 5.0% (w / w) of almond glycends PEG-60; 8.0% (by weight / weight) of glycol distearate; about 2.0% (w / w) of a mixture of poly acp lick; fine end of 13-14 carbon atoms and Laur-eth 7; and sufficient quantity of water destined for Liada.