AU3826800A - Skin cleaning method for eliminating comedones and scales from parts of the skin subjected to the proliferation of candida albicans - Google Patents

Description

WO 00/62756 PCT/FROO/00905 METHOD FOR CLEANSING THE SKIN, INTENDED TO ELIMINATE COMEDONES AftD SQUAMAE FROM PARTS OF THE SKIN SUBJECTED TO PROLIFERATION OF CANDIDA ALBICANS 5 The present invention relates to skin care, in particular for avoiding excessive development of agents responsible for mycoses, by application of compositions corresponding to the definition of cosmetic and body hygiene products which is given by 10 volume V of the Public Health Code in France: "Substances ou pr6parations autres que les m6dicaments, destin6es & etre mises en contact avec les diverses parties superficielles du corps humain ou avec les dents et les muqueuses en vue de les nettoyer, de les 15 prot6ger, de les maintenir en bon 6tat, d'en modifier l'aspect ou d'en corriger l'odeur". (Substances or preparations other than medicaments, intended to be brought into contact with various superficial parts of the human body or with the teeth and the mucous 20 membranes for cleaning them, protecting them, maintaining them in good condition, modifying the appearance thereof and correcting the odour thereof). It relates more precisely to the cleansing of the skin and its protection against fungal agents which may be 25 present on it. It thus allows the skin to be maintained in good condition without the risk of destroying the 2 equilibrium between the skin barriers by virtue of its non-irritation and its safety. It employs aqueous compositions containing an amphoteric surfactant and/or an anionic surfactant, where appropriate supplemented 5 with a thickener, provided in various forms, washing solutions, cleansing lotions, intimate body care gels, body milks, liquid soaps, cleansing gels for the face, solutions for impregnating nonreusable serviettes. In the foam gels for cleansing the skin in 10 which the base contains an anionic surfactant and an amphoteric surfactant, the washing function itself is devolved to the two components, but a foaming function is provided by the amphoteric surfactant. Very broadly, the amphoteric surfactant is an alkylbetaine, in 15 particular an alkylamidopropylbetaine whose alkyl chain comes from lauric, copra or palm kernel acids. The removal of excess sebum is one of the results expected from the skin cleansing action. Hyperseborrhoea actively participates in the appearance of comedones by 20 blocking the pilosebaceous canal. In contrast, the use of irritating or drying products, such as alcoholic solutions or antifungal agents such as triclosan, stimulates in return an overproduction of sebum. The mechanical removal of the transient fungal flora, for 25 which there may be mentioned Candida albicans and Pityrosporum ovalae, is another of the results expected from the skin cleansing action, but efforts have also 3 been made to develop skin cleansing or intimate hygiene gels which combat or prevent the development of fungal strains. For that, use has been made of various antifungal agents. 5 Among the conventional antifungals, there may be mentioned: - salicylic acid; - benzalconium bromide; - benzoic acid; 10 - triclosan, a molecule described here as 5-chloro-2-(2,4-dichlorophenoxy)phenol (CAS: 3380 34-5). - a few surfactants derived from undecylenic acid, in particular the disodium salt of 4-sulpho-{2 15 [(1-oxo-10-undecylenyl)amino]ethyl}butanedioic ester (RN=26650-05-5) (or disodium undecylenamido MEA sulphosuccinate, according to the CTFA name taken from the International Cosmetic Ingredient Directory, 6th edition by the Cosmetic, Toiletry, and Fragrance 20 Association, 1995), and N-(2-hydroxyethyl)undecanamide (RN=20545-92-0 and 40839-40-5) (CTFA: undecylenamide MEA). Some antifungal active ingredients among the most commonly used exhibit, however, a cytotoxic 25 potential in vitro. If the quantity of antifungal agent in the washing base is too high or if its use is too frequent, for example daily, the washing base may be 4 irritating for the user's skin. Conversely, reducing the concentration of the antifungal agent will lead to a washing base which will not be antifungal. It is thus necessary to either reduce the concentration of active 5 agent with the risk of losing in antifungal activity, or to combine it with molecules protecting the integrity of the skin cells which are damaged and inflamed to a greater or lesser degree. These products have other disadvantages. For example, triclosan, 10 declared an irritant for the skin and the eyes during short-term exposures and whose toxicological matter indicate a possible irritation with absorption through the skin during acute exposure and for which a chronic exposure on the skin may lead to cases of contact 15 allergy (Material Safety Data Sheet - Occupational Health Safety, MSDS-OHS 71610), is generally considered by persons skilled in the art as being insoluble in water and leading to formulations which are opaque and unstable to light. 20 As for the derivatives of undecylenic acid, some have already been mentioned for their antibacterial and antifungal activity, in particular the zinc salts of undecylenamido MEA sulphosuccinate (WO-A-9718823, EP-A-23676) and tricarboxylic acid which 25 are derived from the product of Diels-Alder reaction between maleic anhydride and undecylenic acid (EP-A-71025) as well as a few esters (JP 08053326, 5 EP-A-28459), a few quaternary ammonium salts such as N-1-(3-trimethylammoniumpropyl)undecenamide iodide or its methyl sulphate (EP-A-0 872 203). By way of examples, among the most common derivatives of 5 undecylenic acid, there are N-(2-hydroxyethyl)undecenamide (CTFA: undecylenamide MEA), and the sodium salt of 4-sulpho-{2-[(l-oxo-10 undecenyl)amino]ethyl}butanedioic ester, (CTFA: disodium undecylenamide MEA sulphosuccinate), sold 10 respectively under the trade names "REWOCID'U185 or WITCAMIDE 6570" and "REWOCID'SB U185" by the company WITCO. These derivatives are, however, not amphoteric. It has been discovered, unexpectedly, that in addition to the usual characteristics of the betaines 15 (cosurfactant, good foaming power, mild detergent), N-(carboxymethyl)-N,N-dimethyl-3-[(1 oxoundecenyl)amqino]-1-propaminium hydroxide (RN = 98510-75-9, neutral zwitterion form) (CTFA: undecylenamidopropylbetaine) exhibited, besides a 20 fungal activity against Pityrosporum ovalae which can be exploited for the formulation of antidandruff shampoos (FR 99/078683), a sebum flow-controlling activity and an antifungal activity towards Candida Albicans and therefore developed a seborrhoea 25 regulating efficacy, on the one hand, and a fungistatic activity specific for the transient skin flora, on the other hand, which has never been cited up until now.

6 Consequently, it offers the very big advantage of constituting an amphoteric component in a composition for cleansing the skin, itself endowed with the property of maintaining the skin by the regulation of 5 the excess of sebum and of preventing attacks on it which are due to the development of endogenous fungal strains, during opportunistic infections due to Candida albicans. This discovery is exploited according to the invention in the method for limiting the appearance of 10 comedones or eliminating them, and for preventing desquamation due to the proliferation of Candida albicans, which consists in applying to the regions of the skin threatened by the proliferation of Candida albicans, an aqueous cosmetic composition containing 15 amphoteric surfactants and, where appropriate, anionic surfactants, a composition whose characteristic is that part of the amphoteric surfactants therein consists of undecylenamidopropylbetaine. These compositions offer the very big 20 advantage of directly incorporating an antifungal active agent into cleansing gels for intimate use, liquid soaps and cleansing lotions for the face, independently of the other surfactants and of their content, since this agent, undecylenamidopropylbetaine, 25 requires no particular solubilization, and does not require the preparation of a premix which serves as solubilization intermediate. Still more advantageously, 7 these compositions offer another major advantage, that of giving cleansing gels for intimate use, liquid soaps and cleansing lotions for the face, having seborrhoea controlling properties and antifungal properties and 5 containing no irritating active agent. They may thus be used frequently and regularly with no risk of irritation of the skin or of allergic reactions and therefore without producing hypersecretion of sebum leading to the appearance of comedones by blocking the 10 pilosebaceous-type hair follicles. The control, thus obtained by virtue of these compositions, of the flow of sebum gives the very big advantage of not completely destroying, this component which participates in the natural protection of the stratum corneum in some skin 15 attacks (fungi, bacteria, acidic solutions, sunlight). For the purposes of the invention, anionic surfactant is understood to mean one or more compounds chosen from the group consisting of (Cla to C 14 )alkyl sulphates and (Cl 0 to C, 4 )alkyl ether sulphates. The 20 lauryl ether sulphates are anionic surfactants, commonly used by formulators of skin cleansing gels, or cleansing gels for intimate use. For the purposes of the invention, amphoteric surfactant is understood to mean the compounds chosen, 25 alone or in the form of a mixture, from alkylamphocarboxyglycinates, alkylamophocarboxypropionates, alkylamphodiacetates, 8 alkylamphodipropionates, alkylamphoglycinates, alkylamphopropionates, alkyliminopropionates, alkyliminodipropionates, alkylamphopropylsulphonates, alkylbetaines, alkylamidopropylbetaines, alkylsultaines 5 and alkylamidopropylhydroxysultaines. In this list, alkyl- is understood to mean C 10 to C 14 hydrocarbon chains and more especially lauric, copra or palm kernel fatty acid residues or fatty acid residues from equivalent sources. The copra-amidopropylbetaines are 10 preferred amphoteric agents for producing the formulations according to the invention. Undecylenamidopropylbetaine which is the characteristic amphoteric agent of the invention is an alkylamidopropylbetaine on an undecylenic base. It may 15 be prepared according to methods known to persons skilled in the art, in particular following the procedure described in Patent US 3,225,074 (AMERICAN CYANAMID) which consists in reacting undecylenic acid with N,N-dimethyl-1,3-propanediamine (DMAPA) between 20 140 and 200 0 C to form the tertiary amidoamine of formula

CH

3

H

2

C=CH

2

-(CH

2 )s-CO-NH-(CH 2

)

3 -N\

CH

3 which amidoamine is then reacted with monochloroacetic acid in the presence of an alkali metal salt or the 25 corresponding salt of this acid, the reaction occurring 9 in an aqueous medium. The alkali metal chloride, frequently sodium chloride, co-produced during the reaction, is generally left in this aqueous solution of betaine. 5 The compositions of the invention are aqueous solutions in which the content of all the constituents of the washing base (amphoteric and anionic) are within certain limits so as to ensure their physical equilibrium, in particular their homogeneity and their 10 transparency (in the absence of the intentional introduction of pearlescent agents), which limits are naturally subject to some variations depending on the individual, components used. They will be read with the following symbols: An given for anionic components, 15 Amph for amphoteric compounds, Amph representing all the amphoteric agents, AmphU representing undecylenyl betaine, Amph* representing all the amphoteric components excluding undecylenyl betaine. There are thus, on the one hand, as regards 20 the anionic agent/amphoteric agent equilibrium: 5% An+ Amph 5 23.1% 0% 5 An 8.1% 5% 5 Amph 15% on the other hand, as regards the non-undecylenic 25 amphoteric agent/undecylenic amphoteric agent equilibrium: 5% Amph 15% 10 0% Amph* 7.5% 5% Amph 7.5% There will commonly be, for a face lotion, an aqueous composition containing amphoteric surfactants in an 5 amount of 5.5 to 8%, of which undecylenamidopropylbetaine from 5 to 6%, and anionic surfactants in an amount of 0 to 2% expressed by weight of dry extract; for a gel for intimate care, a composition containing amphoteric surfactants in an 10 amount of 7 to 15%, of which undecylenamidopropylbetaine from 5 to 7.5%, and anionic surfactants in an amount of 2 to 4% expressed by weight of dry extract; for a liquid soap, a composition containing amphoteric surfactants in an amount of 9 to 15 15%, of which undecylenamidopropylbetaine of 5 to 7.5%, and anionic surfactants in an amount of 4 to 8.1% expressed by weight of dry extract. A common composition of a skin cleansing gel according to the invention will have, for example, the 20 general composition Sodium lauryl ether sulphate 0 to 8.1% Cocoamidopropylbetaine 1 to 7.5% Undecylenamidopropylbetaine 5 to 7.5% Ordinary ingredients of skin cleansing gels and 25 demineralized water qs 100 11 Common ingredients for the formulation of this type of product enter into these compositions, namely: - thickening agents intended to give the skin 5 cleansing gels, or cleansing gels for intimate use, a sufficient consistency and improved cosmetic qualities. Among the known thickening agents, carbomers (homopolymers of acrylic acids crosslinked with an allyl ether of pentaerythritol, of sucrose or of 10 propylene), esters of PEG, lauryl pyrrolidone, acrylic copolymers and cationic polymers on a natural or synthetic base, including some which are polyquaternium, give, in the application considered, very satisfactory results, given in particular the fact 15 that it has been possible to obtain viscosities greater than 100 mPa.s, preferably of between 1000 mPa.s and 30,000 mPa.s, with these particular products ("CARBOPOL*ULTREZ10" from BF GOODRICH, "ATLAS G-1821" from ICI, "SURFADONELP*300" from ISP, "ACRYSOL*22" from 20 ROHM & HASS, "JAGUARC*162 and "RHODICARET*" from RHONE POULENC, "UCAREPOLYMER*Jr. 400" from AMERCHOL, "MACKERNIUM7*" from JAN DEKKER/MAC INTYRE and "GAFQUAT*755 N" from ISP). These specific thickening agents make it possible to obtain acceptable 25 viscosities when they are used at concentrations of between 0 and 4% relative to the whole composition, preferably of between 0.2 and 2% by weight.

12 - Foam promoters/stabilizers, compounds chosen from the group consisting of alkanolamide of diethanolamine or tertiary amine oxides, which can be used at concentrations of between 1 and 5% by weight 5 relative to the total weight of the composition, but which are increasingly excluded from the formulation for fear of toxicity induced by some of their possible impurities-. The compositions according to the invention 10 may, in addition, contain some customary adjuvants in the field of skin cleansing gels or cleansing gels for intimate use: preservatives, sequestrants, emolients, foam modifiers, colorants, pearlescent agents, moisturizing agents, antiseborrheic agents, vitamins, 15 sunscreens, perfumes. As regards perfumes, it should be noted that the faint odour characteristic of undecenylamidopropylbetaine allows any perfume from the most discrete to the most specific. The use of the customary preservatives, alone 20 or in the form of a mixture, of the phenoxyethanol, methylparaben, ethylparaben, propylparaben and butylparaben type (CTFA nomenclatures, INCI, 6th edition) at concentrations of between 0.25 and 1% by weight relative to the whole composition, proved 25 particularly useful for obtaining an effective and prolonged protection of the foam gels over time.

13 The compositions according to the invention may also contain additional solvents, for example glycols or glycerin which, at concentrations of between 2% and 8% by weight, and more particularly still 5 between 4% and 6% by weight, relative to the whole composition. These solvents participate in the physical stability of the formulations at low temperatures (problems of cloudiness or of growth of crystals in particular). They also promote rapid penetration of the 10 active ingredient into the horny layer and improve the state of the irritated horny layer (hydration of the superficial layers of the epidermis). The pH of these compositions should be between 4.5 and 7.0, rather around 6, for the 15 antifungal activity to be preserved at the best level. The adjustment of the pH to the desired value is conventionally carried out by addition of an organic or inorganic acid or base, for example citric acid, succinic acid, phosphoric acid, sodium hydroxide, 20 sodium carbonate. The washing and antifungal compositions according to the invention are stable (absence of settling out or of phase separation) and homogeneous over time in the temperature range 4-45 0 C both under 25 natural light and under Suntest ageing conditions. They offer good skin tolerance which allows frequent and regular use. They exhibit, in addition, good foaming 14 and washing power, which allows the elimination of the fungal strains present in the superficial layer of the epidermis and good rinsing capacities. Their viscosity may be adjusted to the specific needs of the 5 application. The formulations according to the invention are suitable for the production of transparent products which are only very slightly coloured, having a gel or liquid texture which is viscous to a greater or lesser 10 degree. Concrete examples of formulations will illustrate the invention. EXAMPLES The compositions described below are 15 expressed with percentages by weight of active substances. The corresponding percentages by weight of crude or commercially available products used have been specified. The undecylenamidopropylbetaine used in these 20 examples was synthesized according to the procedure described above. Its composition is established as follows: Undecylenamidopropylbetaine 30.0 ± 2% NaCl 6% max. 25 Undecylenic acid 0.5% max. Tertiary amidoamine 0.5% max. Sodium monochloroacetate < 20 ppm 15 Its pH at 5% in water is 5.8 to 7.5, and its Hazen colour is less than 300. Example 1 : Fungistatic power of 5 undecylenamidopropylbetaine Fungistatic activity towards Candida albicans is understood to mean the property of preventing the growth of this strain during a standard Minimum Inhibitory Concentration experiment, called MIC test. 10 The MIC is determined by incubating the studied strain in dilutions of the product to be tested, and by monitoring the growth of the strain; the MIC value is the concentration between the dilution not leading to a slowing down in bacterial growth and the concentration 15 leading to such a slowing down. A fungistatic activity towards Candida albicans was observed at undecylenamidopropylbetaine concentrations of between 3.5% and 7.5%; a fungistatic efficacy specific for the transient skin flora is therefore 20 developed. Example 2: Curative action - sebumetry tests The test of seboregulatory efficacy is carried out over a period of 15 days; test panel of 15 25 people between 22 and 49 years of age (mean 33.7 years, standard deviation 3.6).

16 A solution containing 5% undecylenamidopropylbetaine was applied once a day to each of the subjects, and then rinsed. The sebumetry index was measured with the 5 sebumetre marketed by the company COURAGE-KHAZKA; its variation is expressed as a percentage of D15 relative to Dl. The results of the measurements show an average reduction in the sebumetry index of 30%, it 10 reaches 60% in some subjects, no subject exhibits an increase in the sebumetry index. From this set of results, it is concluded: - that sebum was eliminated and regulated (decrease of 20 to 60%) on the part of the body where the comedons 15 are usually developed, preventing their appearance, with a solution containing undecylenamidopropylbetaine (Amphoram U), - that the sebumetry index did not increase over any of the subjects, which demonstrates the mild curative 20 action, without irritation, during daily use. Example 3: Preventive action - squamometry tests The test of efficacy of elimination of squamae was carried out over a period of 15 days; test 25 panel of 15 people (see Example 2).

17 A solution containing 5% undecylenamidopropylbetaine was applied once a day to each of the subjects, and then rinsed. The desquamation index was measured with D 5 SQUAME* adhesives, its variation is expressed as a percentage of D1 relative to D1. The results of the measurements show an average decrease in the desquamation index of 25%, it reaches 55% in some subjects. 10 From this set of results, it is concluded: - that the regular application of a solution containing Amphoram U to the skin leads to a decrease in the desquamation of the stratum corneum; - that following this daily use, the conditions 15 favourable to the development of Candida albicans, which are responsible for desquamation, are limited; - that the efficacy of the skin barrier is therefore maintained, which allows prevention against external attacks; 20 - that there is regulation of skin renewal as a result of the protection obtained. Example 4: Transparent cleansing gel for intimate hygiene 25 Sodium lauryl ether sulphate(l 1 3.4 parts by weight Cocoamidopropylbetaine (2) 7.5 parts Undecylenamidopropylbetaine( 3 ) 6 parts 18 Diethanolamine lauramide( 4 ) 1 part PEG-18 Glyceryl oleate/cocoate 2 parts Sodium chloride 1 part Preservative, perfume QS 5 Citric acid QS Demineralized water QS 100 parts Commercial products used .(l) Empicol* EBS 3M (ALBRIGHT & WILSON) 12% (2) Amphoram* C30 (CECA): 25% 10 (3) Amphoram" U (CECA): 20% (4) Mackamide* LMD (MAC INTYRE): 1% (5) Antil* 171 (TH.GOLDSCHMIDT): 2% Characteristics - Fluid gel which is easy to apply, transparent, 15 odourless, completely colourless (58 Hazen), pH = 5.8. - Stable formula, tested at +40C and +45 0 C (exposure for one month to natural light behind a pane of glass, wavelengths above 310 nm) and Suntest (15 days under accelerated ageing in a Suntest-type apparatus; power 20 500 watt/m 2 , 300 to 800 nm). - Forms a nice white foam easy to rinse. - Non-irritating formula intended for regular and frequent use. 25 Example 5: Cleansing lotion for the face Cocoamidopropylbetaine") 1 part by weight Undecylenamidopropylbetaine (2) 5 parts 19 Glycerin 2 parts Propylene glycol 5 parts Preservative, perfume QS Demineralized water QS 100 parts 5 Commercial products used (1) Amphoramo C30 (CECA): 3.3% (2) Amphoram* U (CECA): 16.6% Characteristics - Liquid which is transparent, odourless, and 10 completely colourless (3 Hazen), pH = 5.3. - Stable formula, tested at +4 0 C and +45 0 C (exposure for one month to natural light behind a pane of glass, wavelengths above 310 nm) and Suntest (15 days under accelerated ageing in a Suntest-type apparatus; power 15 500 watt/m 2 , 300 to 800 nm). - Non-irritating formula intended for regular and frequent use. Example 6: Liquid soap for the hands 20 Sodium lauryl ether sulphate" 1 ) 7 parts Cocoamidopropylbetaine (2) 4 parts Undecylenamidopropylbetaine( 3 ) 6 parts Decyl glucoside( 4 ) 2.54 parts Ethylenediaminetetraacetic acid, 25 tetrasodium salt( 5 ) 0.2 part Benzalconium chloride 0.2 part Sodium chloride( 6 ) 1.2 parts 20 Perfume QS Demineralized water QS 100 Commercial products used (1) NEOPON*LOS 2N70 (WITCO) : 10% 5 (2) Amphoram* C30 (CECA): 13% (3) Amphoram* U (CECA): 20% (4) Plantacare* 2000 (HENKEL): 4.8% -(5) EDTA Na4 (PROLABO): 0.2% (6) NORAMIUM*DA 50 (CECA): 0.2% 10 Characteristics - Liquid Soap with good spreadability on the hands, which is transparent, with a slight odour, completely colourless. (40 Hazen), pH = 6.5. - Stable formula, tested at +4 0 C and +45 0 C (exposure 15 for one month to natural light behind a pane of glass, wavelengths above 310 nm) and Suntest (15 days under accelerated ageing in a Suntest-type apparatus; power 500 watt/m 2 , 300 to 800 nm). - Pleasant and soft foam easy to rinse and leaving the 20 skin soft - Non-irritating formula intended for regular and frequent use.

Claims (6)

1. Method for maintaining and cleansing the skin, intended to decrease and regulate the appearance of comedones and to prevent desquamation of the skin, 5 characterized in that an aqueous cosmetic composition containing amphoteric surfactants and, where appropriate, anionic surfactants in which all or part of the amphoteric surfactants consist(s) of an undecylenamidopropylbetaine is applied to the regions 10 of the skin threatened by the proliferation of Candida albicans.

2. Method according to Claim 1, in which the cosmetic composition comprises amphoteric (Amph) surfactants and where appropriate anionic (An) 15 surfactants distributed by weight according to 5% An+ Amph 5 23.1% 0% An 8.1% 5% Amph 15% the distribution of the amphoteric agents between 20 undecylenamidopropylbetaine (AmphU) and the other amphoteric agents (Amph*) which are not undecylenamido propylbetaine taking place according to the weight relationships: 5% 5 Amph 15% 25 0% 5 Amph* 7.5% 5% Amph 7.5% 22

3. Method according to Claims 1 or 2, in which the cosmetic composition corresponds to the formula Sodium lauryl ether sulphate 0 to 8.1% 5 Cocoaminopropylbetaine 1 to 7.5% Undecylenamidopropylbetaine 5 to 7.5% Ordinary ingredients for formulation of a cosmetic composition and demineralized water 76.9 to 94% 10 (percent by weight relative to the composition).

4. Method according to Claims 1 or 2, in which the cosmetic composition is a face lotion containing amphoteric surfactants in an amount of 5.5 to 8% (by weight), of which undecylenamidopropylbetaine 15 from 5 to 6%, and anionic surfactants in an amount of 0 to 2% expressed by weight of dry extract.

5. Method according to Claims 1 or 2, in which the cosmetic composition is a gel for intimate care containing amphoteric surfactants in an amount of 20 7 to 15%, of which undecylenamidopropylbetaine from 5 to 7.5%, and anionic surfactants in an amount of 2 to 4%, expressed by weight of dry extract.

6. Method according to Claims 1 or 2, in which the cosmetic composition is a liquid soap 25 containing amphoteric surfactants in an amount of 9 to 15%, of which undecylenamidopropylbetaine of 5 to 7.5%, and anionic surfactants in an amount of 4 to 8.1%, expressed by weight of dry extract.