EA042158B1 - METHOD FOR PRODUCING COMPOSITION FOR PERSONAL HYGIENE CONTAINING CYSTINE AND COMPOSITION OBTAINED BY THE SPECIFIED METHOD - Google Patents

Description

In the description and claims, the following terms have the meanings specifically related to the present invention, unless the context clearly indicates otherwise.

The phrases in one embodiment and in some embodiments used herein do not necessarily refer to the same implementation variant(s), although they may. In addition, phrases in another embodiment and in certain other embodiments used herein do not necessarily refer to another embodiment, although they may. Thus, as described below, the various embodiments of the invention can be easily combined without departing from the scope or spirit of the invention. In addition, each of the examples is given in connection with various embodiments of the invention, which are intended to be illustrative and not limiting.

Except in the examples or where expressly stated otherwise, all numerical values in the present description, indicating the amount of material or reaction conditions, the physical properties of the materials and/or application, should be understood as modified by the word approximately. All amounts are based on the weight of the final composition, unless otherwise indicated. The present invention is to be considered as embracing all embodiments that are defined in the claims as being multiple dependent on each other, regardless of the fact that the claims can be defined without multiple dependency or redundancy. In defining any concentration or amount range, any particular upper concentration may be associated with any particular lower concentration or amount.

The term "comprising" means including, but not necessarily consisting of or composed of. In other words, the listed steps or options are not exhaustive.

The term skin should be understood to include skin on the face, neck, chest, back, arms (including underarms), hands, legs, buttocks and scalp.

The term "leave-on" composition refers to a composition that is applied to the skin and is not intended to be rinsed off or rinsed off for a certain period of time, in particular hours, in contrast to compositions for cleansing or washing or rinsing the skin, which are removed by rinsing or rinsing off. immediately or a few minutes after application.

Non-solid in relation to the composition means that the composition has a measurable viscosity (measured, for example, using a Brookfield DV-I + viscometer (20 rpm (RPM), RV6 spindle, 30 s, 20 ° C) in the range from 1 to 500 Pa-s, preferably 2 to 100 Pa-s, more preferably 3 to 50 Pa-s.

The term personal care composition refers to any product applied to the human body to improve appearance, sun protection, cleansing, odor control, moisturizing, or general aesthetics. Non-limiting examples of personal care compositions include skin lotions, creams, gels, lotions, sticks, shampoos, conditioners, shower gels, toilet soaps, antiperspirants, deodorants, shaving creams, depilators, pomades, foundations, mascaras, self-tanners and sunscreen lotions.

The term skin cosmetic composition refers to any product applied to the human body to improve appearance, protect against the sun, reduce wrinkles or other signs of photoaging, control odor, brighten skin, even skin tone, or general aesthetics. Non-limiting examples of topical skin cosmetic compositions include skin lotions, creams, gels, sticks, antiperspirants, deodorants, lipsticks, foundations, mascaras, liquid or gel body washes, soaps, self-tanning creams, and sunscreen lotions.

The personal care composition obtained according to the technology of the present invention is preferably a non-rinsing, non-solid skin cosmetic composition, since it is most difficult to include cystine in such compositions due to its low solubility. The increased solubility of cystine in the compositions increases the availability of cystine for greater delivery through the skin and improved feel of the composition on the skin (reduces

- 2 042158 richness).

In one embodiment, the implementation of the composition according to the present invention obtained by the method according to the present invention.

In one embodiment, the method according to the present invention includes the steps of:

a) mixing 0.5 to 10% or 0.5 to 1.3% cystine in a basic aqueous solution at a pH of 9 to 14 or 9 to 12 or 9 to 10 to obtain an aqueous solution of cystine. Said basic aqueous solution is prepared in a suitable strong base, including but not limited to alkali and alkaline earth metal hydroxides, monoethanolamine, diethanolamine, triethanolamine, and mixtures thereof. The greater the amount of cystine, the greater the pH of the stock solution is required. The solution is prepared at room temperature with gentle stirring until visible crystals disappear;

b) mixing said aqueous solution of cystine with a lamellar liquid crystalline or lamellar gel fatty acid-soap phase obtained by neutralization of a C ₁₀ -C ₂₂ fatty acid to obtain a composition containing cystine in the aqueous phase in solubilized form or in the form of crystals, where 90 to 100% of the crystals are 100 nm to 20 µm in size.

When cystine is added to a liquid crystalline or lamellar gel phase, liquid acid-soap from a high pH solution, there is limited growth of cystine crystals and the average particle size of cystine is less than 20 µm. In addition to the small particle size of cystine, the inventors surprisingly found that cystine, when added to and neutralized with fatty acids, also remains solubilized at 150 to 1000 ppm.

Thus, the present invention achieves a cystine crystal size of less than 20 µm to provide a pleasant formulation feel and lack of graininess, while still achieving the desired increased cystine solubility of 150 to 1000 ppm. An additional unexpected benefit observed when adding cystine through the method according to the present invention compared to adding cystine in another way, i. not by the method according to the present invention, lies in the better homogeneity of cystine in the composition. This will provide better surface coverage of cystine when the product is applied to the skin, potentially improving its bioavailability and efficacy. Ultimately, cystine in the form of small crystals also provides a faster dissolution rate compared to the dissolution rate of larger cystine crystals.

The fatty acid must be neutralized to a level that allows the formation of a lamellar liquid crystalline phase or a lamellar gel phase. Generally speaking, a lamellar liquid crystalline or lamellar gel phase for a neutralized fatty acid system will form at a molar ratio of 10:1 to 1:10 (fatty acid:soap). In one embodiment, the fatty acid:soap molar ratio is between 5:1 and 1:5. Alternatively, said ratio is between 3:1 and 1:3. The amount and temperature at which a lamellar liquid crystalline or lamellar gel phase is formed also depends on the length of the fatty acid chain and the type and amount of water present in the formulation. In the basis of the no-rinse cream, the lamellar liquid crystal or lamellar gel is formed at a temperature of 50-60°C.

Crystal size can be measured microscopically.

In one embodiment, the fatty acids used have a chain length in the range of C ₁₀ to C ₂₂ . In one embodiment, the fatty acids have a chain length in the range of C14 to _C20 , or alternatively _C16 and/or _C18 . In one embodiment, the fatty acid is a mixture of C ₁₆ and C ₁₈ in a 2:1 to 1:2 weight ratio.

In one embodiment, the personal care composition has a pH of 3.5 to 8.5. In other embodiments, the personal care composition has a pH of 3.5 to 8. In some embodiments, the personal care composition has a pH of 5 to 7.8. In some embodiments, the personal care composition has a pH of 5 to 7.5.

All additional ingredients described below can be included in the composition at any stage, provided that they do not completely interfere with the formation of the lamellar liquid crystalline or lamellar gel phase.

The compositions may include additional oils.

Suitable oils include emollients, fatty acids, fatty alcohols, thickeners, and combinations thereof. They may be in the form of silicone oils, natural or synthetic esters, hydrocarbons, alcohols and fatty acids. The amounts of emollients can be any of the range from 0.1 to 95%, preferably from 1 to 50%, based on the weight of the composition.

Silicone oils can be divided into volatile and non-volatile. As used herein, the term volatile refers to those materials that have a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably selected from cyclic (cyclomethicone) or linear polydimethylsiloxanes containing 3 to 9, preferably 5 to 6 silicon atoms.

Non-volatile silicone oils used as an emollient material include polyalkylsiloxanes, polyalkylarylsiloxanes, and polyethersiloxane copolymers. Essentially non-volatile polyalkylsiloxanes used herein include, for example, polydimethylsiloxanes with a viscosity

- 3 042158 from 5x10 ^-6 to 0.1 m ² /s at 25°C. Among the preferred non-volatile emollients used in the compositions according to the present invention are polydimethylsiloxanes having a viscosity of from 1x10 ^-5 to about 4x10 ^-4 m ² /s at 25°C.

Another class of non-volatile silicones are emulsifying and non-emulsifying silicone elastomers. Representative of this category is the dimethicone/vinyl dimethicone crosspolymer available as Dow Corning 9040, General Electric SFE 839 and Shin-Etsu KSG-18. Silicone waxes such as Silwax WS-L (dimethicone copolyol laurate) can also be used.

Ester emollients include:

a) alkyl esters of saturated fatty acids having from 10 to 24 carbon atoms. Examples of such substances include behenyl neopentanoate, isononyl isonanoate, isopropyl myristate and octyl stearate;

b) esters of alkoxyacids (ether-esters), such as esters of fatty acids and ethoxylated saturated fatty alcohols;

c) esters of polyhydric alcohols. Esters of ethylene glycol and mono- and di-fatty acids, esters of diethylene glycol and mono- and di-fatty acids, esters of polyethylene glycol (200-6000) and mono- and di-fatty acids, esters of propylene glycol and mono- and di- fatty acids, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glycerol mono- and di-fatty esters, polyglycerol fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol ester and fatty acids, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are acceptable polyol esters. Particularly suitable are the esters of C ₁ -C ₃₀ alcohols of pentaerythritol, trimethylol propane and neopentyl glycol;

d) wax esters such as beeswax, spermaceti wax and tribegenin wax;

e) esters of sugar and fatty acids such as sucrose polybehenate and sucrose polycottonsedate.

Natural ester emollients are mainly based on mono-, di- and triglycerides. Representative glycerides include sunflower oil, cottonseed oil, borage oil, borage seed oil, evening primrose oil, castor and hydrogenated castor oil, rice bran oil, soybean oil, olive oil, safflower oil, shea butter, jojoba oil, and combinations thereof. Emollients of animal origin are represented by lanolin oil and lanolin derivatives. The content of natural esters can be from 0.1 to 20% based on the weight of the compositions.

Hydrocarbons that are suitable cosmetically acceptable carriers include petrolatum, mineral oil, C ₁₁ -C ₁₃ isoparaffins, polybutenes, and in particular isohexadecane commercially available as Permethyl 101A from Presperse Inc.

Fatty alcohols containing from 10 to 30 carbon atoms are another category of cosmetically acceptable carriers suitable for use. Examples of this category are stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol and cetyl alcohol and mixtures thereof.

Preferred are emollients which can be used in particular for products intended to be applied to the face to improve sensory properties and can be selected from the group: polypropylene glycol-14 butyl ether, also known as Tegosoft PBE , or polypropylene glycol-15 (PPG15) stearyl ether such as Tegosoft E, other oils such as esters, in particular isopropyl myristate, isopropyl palmitate, other oils may include castor oils and their derivatives.

Compositions of the present invention preferably include other ingredients to enhance the ability of cystine to produce intracellular GSH synthesis. In another embodiment, the composition contains additional amino acids, in particular either glycine or glutamate, or both. The amino acids included in the composition according to the present invention are presented as L-stereoisomers, since this is the most common and natural isomeric form found in nature. Since the building blocks of naturally occurring proteins found in human skin, hair and nails are amino acids in the L-isomeric form, it is expected that the L-stereoisomeric amino acids found in the personal care products of the present invention may also have a better interaction with these proteins and are inherently more biocompatible than the D stereoisomeric form. In addition, the biological production and intake of L-stereoisomeric amino acids is significantly higher compared to the D-stereoisomeric form. Ultimately, L-stereoisomeric amino acids are the most cost-effective, more sustainable, environmentally friendly, and affordable than D-stereoisomeric amino acids.

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Any of the amino acids included in the present invention may be present in the form of a salt, and the terms cystine, glutamate source, and glycine as used herein also include salts thereof. Such a salt is not particularly limited as long as it is suitable for topical use. For example, salts of inorganic acids or organic acids can be mentioned. As the inorganic acid, for example, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc. can be used, and as the organic acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, lactic acid, tartaric acid, oxalic acid, fumaric acid, maleic acid, citric acid, malonic acid, methanesulfonic acid, and the like. As the base salt, for example, alkali metal salts such as sodium salt, potassium salt and the like, alkaline earth metal salts such as calcium salt, magnesium salt and the like, and the like can be mentioned.

The source of glutamate can be used in the form of its functional equivalents - glutamine, glutamic acid and/or pyroglutamic acid and/or their salts. Pyroglutamic acid (and/or salts thereof) is preferred because it is more stable than glutamine or glutamic acid. In one embodiment, the amino acids in the GSH precursor are cystine and pyroglutamic acid (and/or salts thereof). In one embodiment, the amino acids in the GSH precursor are cystine, pyroglutamic acid, and glycine (and/or salts thereof).

In one embodiment, the composition of the present invention is a leave-on, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (particularly pyroglutamic an acid or a salt thereof, e.g. sodium pyroglutamate) and glycine at a pH of 3.5 to 8.5, in particular at a pH of 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate, and glycine at pH from 3.5 to 8.5, in particular at a pH of 5 to 8.

In one embodiment, a source of glutamate (preferably pyroglutamate) is included in an amount of 0.01 to 10% or alternatively 0.01 to 5% or 0.05 to 1%, alternatively 0.05 to 0 ,5%. In one embodiment, the glycine source is included in an amount of 0.01 to 10%, or alternatively 0.01 to 5%, or 0.05 to 1%, or alternatively 0.05 to 0.5 %.

Thickeners or rheology modifiers may be used as part of the present invention. Typical thickeners include cross-linked acrylates (eg Carbopol 982®), hydrophobically modified acrylates (eg Carbopol 1382®), polyacrylamides (eg Sepigel 305®), polymers and copolymers of acryloylmethylpropane sulfonic acid/its salts (eg Aristoflex HMB® and AVC®), cellulose derivatives and natural gums. Suitable cellulose derivatives include sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, ethylcellulose and hydroxymethylcellulose. Natural gums suitable for the purposes of the present invention include guar, xanthan, sclerotium, carrageenan, pectin, and combinations of these gums. As thickeners, inorganic substances can be used, in particular clays such as bentonites and hectorites, fumed silicas, talc, calcium carbonate and silicates such as magnesium aluminum silicate (Veegum®). The amount of thickener can be from 0.0001 to 10%, typically from 0.001 to 1% or from 0.01 to 0.5%.

Moisture-retaining agents such as polyhydric alcohols may be included. Representative polyhydric alcohols include glycerol, polyalkylene glycols and more preferably alkylene polyols and their derivatives, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and its derivatives, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,2,6-hexanetriol, ethoxylated glycerin, propoxylated glycerin and mixtures thereof. The amount of humectant may be from 0.5 to 50%, preferably from 1 to 15%, based on the weight of the composition.

Skin humectants such as hyaluronic acid and/or its precursor N-acetylglucosamine may be included in the formulation. N-Acetylglucosamine can be found in shark cartilage or shiitake mushrooms and is commercially available from Maypro Industries, Inc. (NY). Other preferred wetting agents include hydroxypropyl-tri(C ₁ -C ₃ -alkyl)ammonium salts. These salts can be obtained by various synthetic methods, in particular by hydrolysis of chlorohydroxypropyl-tri-^-^-alkyl)ammonium salts. The most preferred representative is 1,2-dihydroxypropyltrimonium chloride, where C ₁ -C ₃ -alkyl represents a methyl group. The amount of salt may be from 0.2 to 30%, preferably from 0.5 to 20%, optimally from 1 to 12%, based on the weight of the topical composition, including all ranges included therein.

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Typically the Ci-C3 alkyl component in the quaternary ammonium group will be methyl, ethyl, n-propyl, isopropyl or hydroxyethyl and mixtures thereof. Particularly preferred is the trimethylammonium group, known by the INCI nomenclature (International Cosmetic Ingredients Nomenclature) as the trimonium group. Any anion can be used in the quaternary salt. The anion may be organic or inorganic, provided the material is cosmetically acceptable. Typical inorganic anions are halides, sulfates, phosphates, nitrates and borates. Most preferred are the halides, especially chloride. Organic anionic counterions include methosulfate, toluoyl sulfate, acetate, citrate, tartrate, lactate, gluconate, and benzenesulfonate.

Also other preferred wetting agents that can be used, especially in combination with the aforementioned ammonium salts, include a substituted urea such as hydroxymethylurea, hydroxyethylurea, hydroxypropylurea; bis-(hydroxymethyl)urea; bis-(hydroxyethyl)urea; bis-(hydroxypropyl)urea; N,N'-dihydroxymethylurea; N,N'-dihydroxyethylurea; N,N'-dihydroxypropylurea; N,N,N'-trihydroxyethylurea; tetra(hydroxymethyl)urea; tetra(hydroxyethyl)urea; tetra(hydroxypropyl)urea; N-methyl-N'-hydroxyethylurea; N-ethyl-N'-hydroxyethylurea; N-hydroxypropyl-N'hydroxyethylurea and N,N'-dimethyl-N-hydroxyethylurea. Here, the term hydroxypropyl appears in the sense that is common to the radicals 3-hydroxy-n-propyl, 2-hydroxy-n-propyl, 3-hydroxyisopropyl or 2-hydroxyisopropyl. Most preferred is hydroxyethyl urea available as a 50% aqueous solution from the National Starch & Chemical Division ICI under the trademark Hydrovance.

The amount of substituted urea that can be used in the topical composition of the present invention is in the range of 0.01 to 20%, or 0.5 to 15%, or 2 to 10%.

When an ammonium salt and a substituted urea are used, most preferably at least 0.01 to 25%, or 0.2 to 20%, or 1 to 15% of a humectant such as glycerol is used. Additional moisturizing agents for use in the present invention include petrolatum and/or various aquaporin-acting actives and/or oatmeal.

In some embodiments, the personal care composition, and especially the cosmetic skin care composition of the present invention, includes a sunscreen. Typically, this is a combination of organic and non-organic sunscreens. It is especially important to include both UVA and UVB sunscreens.

The UV-B sunscreen oil may be selected from the group of cinnamic acid, salicylic acid, diphenylacrylic acid, or derivatives thereof. The UV-B sunscreen oil may contain one or more of: octyl salicylate, 3,3,5-trimethylcyclohexyl-2-hydroxybenzoate, ethylhexyl salicylate, 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate, or 2-ethylhexyl- 4-methoxycinnamate (also known as octylmethoxycinnamate or OMC). Such UV-B sunscreen oils are commonly commercially available, such as Octisalate™ (octyl salicylate), Homosalate™ (3,3,5-trimethylcyclohexyl-2-hydroxybenzoate), NeoHeliopan™ (a range of organic UV filters including OMS (Neo Heliopan AV™) and ethylhexyl salicylate (Neo Heliopan OS™)), Octocrylene™ and Milestab 3039™ (2-ethylhexyl-2cyano-3,3-diphenyl-2-propenoate) or Parsol MCX™ (2-ethylhexyl-4-methoxycinnamate)). The amount of UV-B sunscreen oil in the personal care composition may be from 0.1 to 20 wt.%, or from 0.2 to 10 wt.%, or from 0.5 to 7 wt.%, or from 2 to 6 wt.%.

The personal care composition may further comprise a UV-B sunscreen that is water soluble. The UV-B water-soluble sunscreen may also contain phenyl bemidazole sulfonic acid (also known as ensulizol), 4-aminobenzoic acid (also known as para-aminobenzoic acid or PABA), or both.

The personal care composition of any of the above embodiments may further comprise 0.1 to 10 wt % UV-A sunscreen oil. The UV-A sunscreen oil may contain one or more of: 4-tert-butyl-4'-methoxydibenzoylmethane (avobenzone), 2-methyldibenzoylmethane, 4-methyldibenzoylethane, 4-isopropyldibenzoylmethane, 4-tert-methane, butyldibenzoylmethane, 2,4- dimethyldibenzoylmethane, 2,5-dimethyldibenzoylmethane, 4,4'-diisopropyldibenzoylmethane, 2-methyl-5-isopropyl-4'-methoxydibenzoylmethane, 2-methyl-5-tert-butyl-4'-methoxydibenzoylmethane, 2,4-dimethyl-4 '-methoxydibenzoylmethane, 2,6-dimethyl-4-tert-butyl-4'-methoxydibenzoylmethane, diethylaminohydroxybenzoylhexylbenzoate, ecamsul or methyl anthranilate. The amount of UV-A sunscreen oil in the personal care composition may be 0.5 to 7% by weight, or 1 to 5% by weight.

Additional suitable sunscreen oils suitable for use in personal care formulations include those commercially available from BASF Corporation: Uvinul T-150 (ethylhexyl triazone; UV-B sunscreen oil), Uvinul A Plus (diethylaminohydroxybenzoylhexylbenzo

- 6 042158 at; UV-A sun oil), Tinosorb S (bis-ethylhexyloxyphenol methoxyphenyltriazine; UV-A and UV-B sun oil), Tinosorb M (methylene-bis-benzotriazolyltetramethylbutylphenol; UV-A and UV-B sun oil). The composition of personal care compositions may also contain bisdisulizone disodium.

A particularly preferred combination of UV-A and UV-B sunscreen oils is avobenzone and 2-ethylhexyl-4-methoxycinnamate.

In some embodiments, the sunscreen is an inorganic sunscreen. Examples of inorganic sunscreens suitable for use in the skin care composition of the present invention include, but are not limited to, micronized titanium dioxide, zinc oxide, polyethylene, and various other polymers. The term finely divided refers to particles with an average size in the range from 10 to 200 nm, alternatively, from 20 to 100 nm. The amount of sunscreen, when present in a skin care composition according to some embodiments of the present invention, may be 0.1 to 30%, alternatively 2 to 20%, alternatively 4 to 10%, based on weight of the composition.

There is information that indicates that sources of selenium, such as selenomethionine, are an important component, along with the amino acids that make up GSH, to ensure intracellular GSH biosynthesis. Within the scope of the present invention, it has been found that a source of selenium is not necessary and in fact is redundant in order to achieve the intracellular increase in GSH content according to the present invention. Although a source of selenium may be included, it is preferably avoided in the topical skin care compositions of the present invention because it is recognized as a skin sensitizer in some regulatory frameworks. Accordingly, the amount of selenium in the compositions according to the present invention is from 0 to a maximum of 0.1% or at most 0.05%, optimally not more than 0.01%.

The composition according to the present invention preferably contains a skin lightening compound to achieve optimum skin lightening performance at an optimum cost. Examples of substances are placental extract, lactic acid, resorcinols (4-substituted, 4,5-disubstituted and 4,6-disubstituted, in particular 4-hexyl, 4-methyl, 4-butyl, 4-isopropyl, phenylethylresorcinols), arbutin, kojic acid, ferulic acid, nicotinamide and its derivatives, hydroquinone, resorcinol derivatives, including disubstituted resorcinols, and combinations thereof. In one embodiment, such a skin lightening compound is a tyrosinase inhibitor, most preferably a compound selected from the group consisting of kojic acid, nicotinamide and its derivatives, hydroquinone, and others (non-4-substituted resorcinols). In addition, dicarboxylic acids represented by the formula HOOC-(C _x H _y )-COOH, where x = 4 to 20 and y = 6 to 40, such as azelaic acid, sebacic acid, oxalic acid, succinic acid, fumaric acid , octadecenedioic acid (eg Arlatone DC) or salts or mixtures thereof, most preferably fumaric acid or a salt thereof, especially the disodium salt. The combination of 12HSA (12-hydroxystearic acid) with fumaric acid or salts thereof has been found to be particularly advantageous, especially for skin lightening formulations. The content of these agents may be from 0.1 to 10%, preferably from 0.5 to 2%, based on the weight of the composition. Preferably, nicotinamide and/or 4-alkyl-resorcinol and/or 12-hydroxystearic acid is used as the skin-lightening co-active agent according to the present invention.

Another preferred ingredient in the compositions of the present invention is retinoid. As used herein, the term retinoid includes all natural and/or synthetic analogs of vitamin A or retinol-like compounds that have the biological activity of vitamin A in the skin, as well as geometric isomers and stereoisomers of these compounds. The retinoid is preferably retinol, retinol esters (e.g. C ₂ -C ₂₂ -alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinal and/or retinoic acid (including all-trans retinoic acid and/or 13-cis- retinoic acid), more preferably retinoids other than retinoic acid. These compounds are well known in the art and are commercially available from a number of sources such as Sigma Chemical Company (St. Louis, MO) and Boerhinger Mannheim (Indianapolis, IN). Other retinoids that are applicable here are described in US patent No. 4677120, issued June 30, 1987 Parish et al.; US Pat. No. 4,885,311 issued 5 December 1989 to Parish et al.; US Pat. No. 5,049,584 issued September 17, 1991 to Purcell et al.; US Pat. No. 5,124,356 issued June 23, 1992 to Purcell et al.; and U.S. Patent Reissue 34075 issued September 22, 1992 to Purcell et al. Other suitable retinoids are tocopheryl retinoate [tocopherol ester of retinoic acid (trans- or cis-)], adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid} and tazarotene (ethyl-6 -[2-(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate). Preferred retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retinal, and combinations thereof. Compositions according to this invention may contain a safe and effective amount of reti

- 7 042158 noida, so that the resulting composition is safe and effective for regulating the state of keratin tissue, preferably for regulating visible and/or palpable inhomogeneities in the skin, more preferably for regulating signs of skin aging, even more preferably for regulating visible and/or palpable irregularities in skin texture associated with aging. The compositions preferably contain 0.005 to 2% or 0.01 to 2% retinoid. Retinol is preferably used in an amount of 0.01 to 0.15%; retinol esters are preferably used in an amount of 0.01 to 2% (eg 1%); retinoic acids are preferably used in an amount of 0.01 to 0.25%; tocopheryl retinoate, adapalene and tazarotene are preferably used in an amount of 0.01 to 2%.

Various plant extracts may optionally be included in the compositions of this invention. Illustrative examples are pomegranate, white birch (Betula Alba), green tea, chamomile, licorice, and combinations of these extracts. The extracts can be either water soluble or water insoluble and contained in a solvent which is respectively hydrophilic or hydrophobic. Water and ethanol are the preferred extract solvents.

Materials such as resveratrol, alpha-lipoic acid, ellagic acid, kinetin, retinoxytrimethylsilane (available from Clariant Corp. under the trademark Silcare 1M-75), dehydroepiandrosterone (DHEA) and combinations thereof may also be included. Ceramides (including ceramide 1, ceramide 3, ceramide 3B, ceramide 6 and ceramide 7) and pseudoceramides can also be used in many of the compositions of the present invention, however, these materials can also be excluded. The amount of these materials can be from 0.000001 to 10%, preferably from 0.0001 to 1%.

The personal care composition may further comprise from about 0.1% to about 8% by weight of a film-forming polymer. Such film-forming polymers include, but are not limited to, polyalkyleneoxy-terminated polyamides (e.g., INCI nomenclature: polyamide-3, polyamide-4), polyether polyamides (e.g., INCI nomenclature: polyamide-6), blended polyamides with acid-terminated groups (eg, INCI nomenclature: polyamide-7); and poly(ester-amides) with terminal esters (eg, INCI nomenclature: polyamide-8). Such film-forming polymers can be synthesized or purchased, such as the Sylvaclear™ product line from Arizona Chemical Company, and the LLC and OleoCraft™ product line from Croda International PLC. Film-forming polymers also include, but are not limited to, INCI polyester-5 (e.g., Eastman AQ™ 38S polymer), PPG-17/IPDI/DMPA copolymer (e.g., Avalure™ UR 450 polymer), acrylate copolymer (e.g., polymer Avalure™ AC 120) and polysaccharides such as xylogel (tamarin gum), lotus bean gum, tara gum, beta-glucan, pullulan, carboxymethyl cellulose, hydroxypropyl cellulose, sodium alginate, potato starch, carrageenan. The film-forming polymer may contain combinations of any two or more of the polymers mentioned above. The amount of film-forming polymer in the personal care composition may be from 0.1 to 8% by weight.

Desirably, preservatives are included in the composition of the present invention to protect against the growth of potentially harmful microorganisms. Suitable conventional preservatives for the compositions of this invention are parahydroxybenzoic acid alkyl esters. Other preservatives that have come into use recently include hydantoin derivatives, propionate salts, and various quaternary ammonium compounds. Cosmetic chemists are familiar with the appropriate preservatives and select them regularly to perform a preservative test and ensure product stability. Particularly preferred preservatives are iodopropynyl butyl carbamate, phenoxyethanol, caprylyl glycol, C ₁ . ₆ parabens (especially methylparaben and/or propylparaben), imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol. Preservatives should be selected taking into account the application of the composition and possible incompatibilities between preservatives and other ingredients in the emulsion. Preservatives are preferably used in amounts ranging from 0.01 to 2%. A particularly preferred combination is octocrylene and caprylyl glycol, since it has been disclosed that caprylyl glycol enhances UV-A and UV-B protection.

Suitable antifungal agents for inclusion in personal care compositions are well known to those skilled in the art. Examples include, but are not limited to, climbazole, ketoconazole, fluconazole, clotrimazole, miconazole, econazole, etaconazole, terbinafine, salts of any one or more of them (e.g., hydrochloride salts), zinc pyrithione, selenium disulfide, and combinations of any two or more of them.

In some embodiments, the personal care compositions of the present invention include vitamins. Examples of vitamins are vitamin A (retinol), vitamin B2, vitamin B3 (niacinamide), vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K and biotin. You can also use derivatives of vitamins. For example, vitamin C derivatives include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate, and ascorbyl glycoside. Vitamin E derivatives include toko

- 8 042158 pheryl acetate, tocopheryl palmitate and tocopheryl linoleate. You can also use DL-panthenol and its derivatives. In some embodiments, the vitamin B6 derivative is pyridoxine palmitate. Flavonoids can also be used, in particular glucosylhesperidin, rutin and soy isoflavones (including genistein, daidzein, equol and their glucosyl derivatives) and mixtures thereof. The total amount of vitamins or flavonoids, when present, may be in the range of 0.0001 to 10%, alternatively 0.001 to 10%, alternatively 0.01 to 10%, alternatively 0.1 to 10%, alternatively 1 to 10%, alternatively 0.01 to 1%, alternatively 0.1 to 0.5%.

In some embodiments, the personal care compositions of the present invention comprise an enzyme, such as, for example, oxidases, proteases, lipases, and combinations thereof. In some embodiments, the personal care compositions of the present invention comprise superoxide dismutase, commercially available as Biocell SOD from Brooks Company, USA.

In some embodiments, the personal care compositions of the present invention comprise desquamation promoters. In some embodiments, the personal care compositions of the present invention comprise desquamation promoters at a concentration of 0.01 to 15%, alternatively 0.05 to 15%, alternatively 0.1 to 15%, alternatively 0.5% up to 15%.

Illustrative examples of desquamation promoters include monocarboxylic acids. Monocarboxylic acids may be substituted or unsubstituted with a carbon chain length of up to 16 carbon atoms. In some embodiments, the carboxylic acids are alpha hydroxy carboxylic acids, beta hydroxy carboxylic acids, or polyhydroxy carboxylic acids. The term acid means the content in the composition of not only the free acid, but also its salts and C ₁ -C ₃₀ -alkyl or aryl esters and lactones, formed upon removal of water with the formation of cyclic or linear lactone structures. Typical acids include glycolic, lactic, malic and tartaric acids. In some embodiments, the salt is ammonium lactate. In some embodiments, the beta-hydroxycarboxylic acid is salicylic acid. In some embodiments, phenolic acids include ferulic acid, salicylic acid, kojic acid, and salts thereof.

In some embodiments, at least one additional component may be present in an amount of 0.000001 to 10%, alternatively 0.00001 to 10%, alternatively 0.0001 to 10%, alternatively 0.001 to 10%, alternatively 0.01 to 10%, alternatively 0.1 to 10%, alternatively 0.0001 to 1% by weight of the composition. Compositions according to the present invention may contain dyes, opacifiers or abrasives. Colorants, opacifiers or abrasives may be present in a concentration of 0.05 to 5%, alternatively 0.1 to 3% by weight of the composition.

In some embodiments, the personal care product of the present invention may also contain a peptide, such as, for example, the commercially available pentapeptide derivative, Matrixyl™, which is commercially available from Sederma, France. In another example, in some embodiments, the personal care product of the present invention may also contain carnosine.

Compositions according to the present invention may contain a wide range of other optional components. The Cosmetic Ingredient Handbook of the CTFA Cosmetic Ingredient Handbook, Second Edition, 1992, which is incorporated herein by reference in its entirety, describes a wide range of non-limiting cosmetic and pharmaceutical ingredients commonly used in the cosmetic care industry. skin for topical application, which are suitable for use in the composition according to the present invention. Examples include antioxidants, binders, biological additives, buffering agents, colorants, thickeners, polymers, binders, fragrances, moisture-retaining agents, matting agents, conditioners, exfoliating agents, pH adjusters, preservatives, natural extracts, essential oils, skin sensitizers , skin soothing agents and skin healing agents.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, eg sodium pyroglutamate) and nicotinamide, at pH 3.5 to 8.5.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glycine, and nicotinamide, with pH 3.5 to 8.5, in particular pH 5 to 8.

In one embodiment, the composition of the present invention is a leave-on, non-solid composition in the form of a personal care emulsion, topical emulsion, lotion, gel, cream, or fast-absorbing cream containing a precursor

- 9 042158 glutathione, which contains cystine, glutamate (in particular pyroglutamic acid or its salt, for example sodium pyroglutamate), glycine and nicotinamide, at a pH of 3.5 to 8.5, in particular at a pH of 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, e.g. sodium pyroglutamate) and one or more of 4-hexylresorcinol, 4-ethylresorcinol, 4-isopropylresorcinol, 4-butylresorcinol and 4-(1-phenylethylresorcinol) at a pH of 3.5 to 8.5.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, e.g. sodium pyroglutamate), glycine and 4-hexylresorcinol, at a pH of 3.5 to 8.5, in particular at a pH of 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, for example sodium pyroglutamate), glycine and 4-butylresorcinol, at a pH of 3.5 to 8.5, in particular at a pH of 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, for example sodium pyroglutamate), glycine and 4-(1-phenylethyl)resorcinol at pH 3.5 to 8.5, in particular pH 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, e.g. sodium pyroglutamate), glycine and 2-cyclopentyl-5-pentylresorcinol at pH 3.5 to 8.5, in particular pH 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, for example sodium pyroglutamate), glycine and 5-pentyl-2-isopropylresorcinol at pH 3.5 to 8.5, in particular at pH 5 to 8.

In one embodiment, the composition of the present invention is a non-rinsing, non-solid composition in the form of a personal care, topical emulsion, lotion, gel, cream, or rapidly absorbing cream containing a glutathione precursor that contains cystine, glutamate (in particular, pyroglutamic acid or a salt thereof, e.g. sodium pyroglutamate), glycine and 5-ethyl-2-cyclopentylresorcinol, at a pH of 3.5 to 8.5, in particular at a pH of 5 to 8.

composition form.

Compositions according to the present invention can be used as they are. Alternatively, the composition according to the present invention may be a component of the final product, which is a water-in-oil or oil-in-water emulsion or multiple emulsions. The compositions according to the present invention are preferably non-rinsing compositions. The compositions of the present invention are preferably leave-in formulations that are left on the skin. These leave-in compositions are to be distinguished from compositions which are applied to the skin and subsequently removed either by washing, rinsing, rubbing or the like, either after or during application of the product. Surfactants commonly used for rinse-off compositions have physico-chemical properties that enable them to form a foam/foaming liquid when gently rinsed; they may consist of mixtures of anionic, cationic, amphoteric and non-ionic surfactants. Surfactants used in leave-on compositions, on the other hand, need not have such properties. Rather, since the no rinse compositions are not intended to be rinsed off, they must be non-irritating and therefore it is necessary to minimize the total surfactant content and the total anionic surfactant content of the no rinse formulations.

- 10 042158 compositions. The total content of surfactant in the compositions according to the present invention is preferably from 1 to not more than 15%, more preferably less than 10%, most preferably not more than 9%, optimally, not more than 6%.

In some embodiments, anionic surfactants are present in the leave-in skin care composition in an amount of from 0.01 to no more than 5 wt.% based on the weight of the composition, alternatively, from 0.01 to 4 wt.% in based on the weight of the composition, alternatively, from 0.01 to 3 wt.%, based on the weight of the composition, alternatively, from 0.01 to 2 wt.%, based on the weight of the composition, alternatively, essentially absent (less than 1%, or less than 0.1%, or less than 0.01%). In some embodiments, the total surfactant content of the skin care compositions is not more than 15%, alternatively, less than 10%, alternatively, not more than 9%.

In some embodiments, the surfactant is selected from the group consisting of anionic, nonionic, cationic, and amphoteric active agents.

In some embodiments, the nonionic surfactants are C ₁₀ -C ₂₀ fatty alcohol or hydrophobic acid surfactants condensed with 2-100 moles of ethylene oxide or propylene oxide per mole of hydrophobic substance; C ₂ -C ₁₀ -alkylphenols condensed with 2-20 mol of alkylene oxide; esters of mono- and di-fatty acids and ethylene glycol; fatty acid monoglyceride; sorbitan, mono- and di-C ₈ -C ₂₀ fatty acids and polyoxyethylene sorbitan, as well as combinations thereof. In some embodiments, the nonionic surfactant is selected from the group consisting of alkyl polyglycosides, saccharide fatty amides (eg, methylgluconamides), and trialkylamine oxides.

Amphoteric surfactants suitable for use in skin care compositions according to some embodiments of the present invention include cocoamidopropyl betaine, C ₁₂ -C ₂₀ trialkyl betaines, cocoamidopropyl hydroxysultaine, sodium lauroamphoacetate, and sodium laurodiamphoacetate.

Anionic surfactants suitable for use in skin care compositions according to some embodiments of the present invention include soap, alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C ₈ -C ₂₀ acyl isethionates, C ₈ -C ₂₀ alkyl ether phosphates, C ₈ -C ₂₀ sarcosinates, C ₈ -C ₂₀ acyllactylates, sulfoacetates, and combinations thereof.

The most preferred format are fast-absorbing cream bases and creams and lotions based on oil-in-water emulsions. The basis for a fast-absorbing cream consists of 5-40% fatty acids and 0.1-20% soap. In such creams, the fatty acid is preferably essentially a mixture of stearic acid and palmitic acid, and the soap is preferably the potassium salt of a mixture of fatty acids, although other counterions and mixtures thereof may be used. The fatty acid in a fast absorbing cream base is often made using hystric acid, which is essentially (typically about 90 to 95%) a mixture of stearic acid and palmitic acid. A typical hystric acid contains about 52-55% palmitic acid and 45-48% stearic acid of the total palmitin stearin mixture. Thus, the incorporation of hysteric acid and its soap to provide a fast-absorbing cream base is within the scope of the present invention. It is particularly preferred that the composition contains more than 7%, preferably more than 10%, more preferably more than 12% fatty acids. A typical facial cream base is structured with a crystallization network and is sensitive to the addition of various ingredients.

In some embodiments, the personal care composition is in the form of a shampoo. In some embodiments, the personal care compositions of the present invention are formulated as a deodorant. In some embodiments, the personal care compositions of the present invention are formulated as an antiperspirant, for example, according to the formulations described in US Pat. No. 7,282,471.

In some embodiments, the personal care compositions of the present invention are formulated as disposable wipes according to the formulations described in US Pat. No. 7,282,471.

Method of using compositions for skin care.

In some embodiments, the skin care composition is applied topically to a person's skin. In some embodiments, the skin care composition provides at least one benefit selected from the group consisting of: skin conditioning, skin smoothing, reduction of wrinkling or signs of skin aging, reduction of skin inflammation, reduction of dryness, reduction of age spots, reduction of sunburn. and skin lightening.

In some embodiments, a small amount of the skin care composition, e.g., 1 to 5 ml, is applied to exposed skin from a suitable container or applicator and, if necessary, then spread over the surface and/or rubbed into the skin using the hand or fingers , or a suitable device. Alternatively, a small amount of the skin care composition, for example 1 to 5 ml, is applied to the unprotected area of the skin from a suitable container.

- 11 042158 ner or applicator and then covered with a mask, non-woven or film-forming material.

Further, the present invention is described using the following examples, which together with the above description illustrate some embodiments of the invention in non-limiting examples.

Example 1

In example 1 investigated the recrystallization of cystine from a solution with a high pH.

Soap/acid emulsions were prepared using hysteric acid (55% palmitic acid/45% stearic acid) by melting the hysteric acid at 75° C. and adding this molten acid to the aqueous phase containing KOH. This resulted in an acid/soap mixture that had a pasty consistency. Next, to said acid/soap mixture as a high pH solution was added solubilized cystine in a high pH solution. Depending on the addition procedure, differences were obtained in the final compositions.

Acid/soap mixtures were prepared according to the following scheme.

Table 1

Sample A IN WITH Aqueous phase 1 (heated to 75°C) Water 79.7 77.72 77.72 KOH (45%) 1.2 1.17 1.17 cystine 0.22 - - Oil phase (heated to 75°C) % wt. % wt. % wt. hysteric acid 18.87 18.4 18.4 Water phase 2 Cystine solution (8% in 3% NaOH) was added at 75°С 2.71 Cystine solution (8% in 3% NaOH) was added at 55°С 2.71 Cystine crystal size (in microns) 20-50 20-50 1-2

Composition A was prepared by dissolving cystine in a hot KOH solution. Next, molten hysteric acid was added to this hot (75° C.) aqueous solution of cystine, stirred, and the mixture was allowed to cool to room temperature with stirring.

Composition B was prepared by adding molten hysteric acid to a hot KOH solution and adding a high pH cystine solution while mixing all ingredients at 75°C.

Composition C was prepared by adding molten hysteric acid to a hot KOH solution, thereby making soap, cooling the soap to 50°C, and then adding a high pH cystine solution.

The resulting acid/soap mixtures were analyzed under a microscope for the formation of cystine crystals.

Composition A - at 10-fold increase at room temperature, the formation of cystine crystals with a size of 20-50 μm was shown.

Composition B - at 25x magnification at 80°C, the formation of cystine crystals of 20-50 μm in size was shown.

Composition C - at 25x magnification at 80°C, only very small particles were shown to form in the range of 1-2 µm.

The addition of the cystine solution to the acid/soap mixture at 50-60° C. is preferred because very small particles are formed. At this temperature, most acid/soap exists as lamellar liquid crystals or lamellar gel with a very thin aqueous layer providing a confining environment for cystine crystal growth. When cystine was added to a mixture of fatty acid soap from a high pH solution at a time after which one of its constituent phases was a lamellar liquid or lamellar gel phase, this resulted in limited growth of cystine crystals with an average cystine particle size of less than 20 µm. When the same experiment was carried out with the addition of cystine at a temperature of 75-80°C, when it was in the form of an oil-in-water emulsion, the cystine crystals had a significantly larger size: more than 20 μm (see Table 1).

Example 2

Additional samples were prepared with decreasing concentrations of cystine to establish the solubility limit of cystine in the acid/soap mixture. Samples in table. 2 were obtained by method A of the table. 1.

- 12 042158

table 2

Sample D E F Water with zaza KOH (45%) 1.2 1.2 1.2 cystine 0.26 0.11 0.07 Water Ven. quantity Ven. quantity Ven. quantity Oil phase % wt. % wt. % wt. hysteric acid 18.9 18.9 18.9 Presence of crystals Yes Yes No

The samples were evaluated under a microscope on a hot tablet at 80°C. Samples D and E showed the presence of cystine crystals, sample F did not contain any crystals, even after storage for 7 days. This indicates a cystine solubility of more than 700 ppm in acid/soap media with hysteric acid.

Example 3

In Example 3, a modified system was tested that contained Brij 35 surfactant. Composition examples are shown in Table 1. 3 below. Samples in table. 3 were obtained by method C from table. 1.

Table 3

Sample G H I Water with zaza KOH (45%) 1.2 1.2 1.2 cystine 0.23 0.13 0.06 Water Ven. quantity Ven. quantity Ven. quantity Oil phase % wt. % wt. % wt. hysteric acid 19.1 19.1 19.1 Brij 35 2.2 2.2 2.2 Presence of crystals Yes Yes No Size (microns) 1-2 1-2 -

Given in table. 3, the results illustrate the fact that other ingredients can be added to the compositions of the present invention as long as the intact structure of the lamellar bilayer liquid crystal or liquid gel structure is not disturbed. Similar results were obtained when the solubility was determined at a minimum concentration of more than 600 ppm.

Example 4

Additional samples of lamellar liquid crystal or lamellar gel or lamellar gel phase were prepared using a non-ionic surfactant instead of a fatty acid-soap mixture to assess whether increased solubility is achieved only due to lamellar liquid crystal or lamellar gel or lamellar gel phase. phase or also due to the presence of fatty acids. An additional system was tested using non-ionic tetraethylene glycol-mono to decyl ether surfactant C12EO4. The concentration of this surfactant was chosen to form a lamellar liquid crystal or lamellar gel or lamellar gel phase in an aqueous solution. Pschsteen was added to the lamellar liquid crystal or lamellar gel phase as a high pH solution and then neutralized with a citric acid solution. For all four concentrations obtained, the formation of small crystals was observed. In this case, solubility experiments showed a cystine solubility of less than 200 ppm.

- 13 042158

Sample J No fatty acid Table 4 M TO L C12EO4 59.3 62.5 62.1 61.5 KOH (45%) 0.1 0.05 0.033 0.01 cystine 0.2 0.1 0.07 0.02 Solution 2.5 1.2 0.9 0.3

citric acid, 4%

Water DOST, quantity DOST, quantity DOST, quantity DOST, quantity Availability Yes Yes Yes Yes crystals Size 1-2 1-2 1-2 1-2

crystals (microns)

Non-ionic surfactants do not neutralize high pH cystine solutions with agitation, and the addition of a very low pH aqueous phase for neutralization was necessary. From the results in the table above, it can be seen that the cystine crystals formed were small, indicating that the presence of a lamellar liquid crystalline or lamellar gel phase limited crystal growth. To lamellar liquid crystal or lamellar gel using only C12EO4 ethoxylated surfactant with addition of citric acid as an acidic solution was added cystine in a high pH solution. The results obtained for the present invention indicate that, although in the latter case, the small size of the crystals was preserved, nevertheless, the authors did not achieve any increase in the solubility of cystine beyond its natural solubility of 100 ppm. This was due to the lack of fatty acids.

Example 5

The solubility of cystine was determined in the presence of various fatty acids. The solubility of cystine in the presence of fatty acids was determined by solubilizing excess L-cystine at high pH (in 0.050.1% (wt.) NaOH) and neutralizing the resulting solution with a selected fatty acid or mixture of fatty acids to a neutral pH in the range of 5-7. The precipitate after neutralization was equilibrated with a saturated solution for at least 72 hours. The solutions were then filtered through a syringe filter with 0.45 μm polytetrafluoroethylene (PTFE) or nylon (for C12) and analyzed by HPLC to determine the concentration of cystine (Phenomenex Synergi Hydro RP column 4 µm, 250x4.6 mm, mobile phase - 0.2% formic acid in water, isocratic mode, flow rate 1 ml/min, column temperature 30°C, UV detector at 250 nm). The results are shown in table. 5.

Table 5

Acid pH Solubility of cystine, ppm %RSD* Octane (C8) 5.3 188.1 6.1 Dean (SU) 6.8 262.3 11.8 Dodecanoic (С12) with NaOH 7.6 575 13.4 Dodecane (C12) with KOH 7.6 490.6 9.5 Oleic acid (018:1) 7.3 246.8 6.6 Mixture **С12/oleic (molar ratio 0.25) 7.3 253 2.7 Malonic 6.3 162.4 2.3 Amber 6.3 150.4 7 Adipine 7 171.1 7.4 Maleic 6.6 181.6 1.5

* %RSD means % Relative Standard Deviation for triplicate (%RSD = SD/mean x100%).

** Eutectic mixture C12/oleic acid.

Cystine remained solubilized at 150 to 600 ppm when added to fatty acids.

- 14 042158 slots or when neutralized with their help. The solubilized amount depends on the type of fatty acid and chain length, as indicated in the table. 5.

Example 6

Compositions for personal care according to the present invention are illustrated in the tables below. All numerical values in the tables reflect wt.% in the composition.

Table I

Oil-in-water formulations, lotions and creams

OW-2 OW-3 OW-4 OW-5 Water Up to 100 Up to 100 Up to 100 Up to 100 Glycerol 1-40 1-5 1-10 1-40 propylene glycol 0-5 Butylene glycol 0-5 0-5 Carbomer 0.03-1 Ammonium copolymer acryloyldimethyltaurate/vinyl pyrrolidone (VP) 0.03-1 0.01-1 Copolymer styrene/acrylates 0.01-1 xanthan gum 0.01-1 EDTA 0.01- 0.01 0.01-1 0.01-1 0.01-1 preservative 0.02-2 0.02-2 0.02-2 0.02-2 titanium oxide 0,0IIO 0,0IIO 0,0IIO 0,0IIO Dye/pigment 0-5 0-5 0-5 0-5 Triethanolamine / sodium hydroxide / potassium hydroxide 0.01-3 0.01-3 0.01-3 0.01-3 Stearic acid 0.01-5 0.01-5 0.01-5 0.01-5 Isopropyl myristate 0,0IIO Capric/caprylic triglyceride 0,0IIO C12-C15 alkyl benzoate 0,0IIO Mineral oil 0,0IIO Glyceryl stearate 0.01-5 Stearet-2 0.01-5 0.01-5 Stearet-21 0.01-5 PEG100 stearate 0.01-2 0.01-5 Potassium cetyl phosphate 0.01-2 Tween20 0.01-5 cetyl alcohol 0.01-4 0.01-4 Dicaprylyl carbonate 0.01-5 Ethylhexylmethoxycinnamate 0.01-6 Butylmethoxydibenzoylmethane 0.01-3 0.01-3 0.01-3 Enzulizol 0.01-4 Octinoxate Octisalate 0.01-5 0.01-5 Octocrylene 0,0IIO 0,0IIO Homosalat 0,0IIO Dimethicone 0,0IIO 0,0IIO Cyclomethicone o,oils Niacinamide 0-5 0-5 0-5 0-5

- 15 042158

Perfume 0-2 0-2 0-2 0-2 Glutamine / sodium pyrrolidone carboxylate (PCA) 0,0IIO 0,0IIO 0,0IIO 0,0IIO Glycine 0,0IIO 0,0IIO 0,0IIO 0,0IIO cystine 0.001- 2 0.001- 2 0.001- 2 0.001- 2 2-Cyclopentyl-5-pentylresorcinol 0.001- 3 5-Pentyl-2-isopropylresorcinol 0.001- 3 5-Pentyl-2-cyclopentylresorcinol 0.001- 3 0.001- 3

Table II

Lotions or creams of the water-in-oil type for topical application

WO-1 WO-2 Water Up to 100 Up to 100 Glycerol 0-70 1-70 propylene glycol 0-5 Butylene glycol 0-5 Disteardymmonium hectorite 0.01-1 0.01-1 EDTA 0.01-.01 0.01-1 preservative 0.02-2 0.02-2 TU2 0-10 0.01-10 Dye/Pigment 0-5 0-5 TEA/sodium hydroxide/potassium hydroxide 0-3 0.01-3 Stearic acid 0-5 0.01-5 Isopropyl myristate 0-10 capric/caprylic triglyceride 0-10 C12-C15 alkyl benzoate 0-10

- 16 042158

Mineral oil 0-10 Glyceryl stearate 0-5 Dimethicone copolyol 0-5 0.01-5 Cetyl-PEG/PPG-10/1 dimethicone 0-5 Stearet-2 0-2 Sucrose distearate 0-2 0.01-2 cetyl alcohol 0-2 0.01-2 Ethylhexylmethoxycinnamate 0-6 0.01-6 Butylmethoxydibenzoylmethane 0-3 0.01-3 Enzulizol 0-4 Octinoxate 0-7.5 Octisalate 0-5 Octocrylene 0-10 Homosalat 0-10 Dimethicone 0-10 Cyclomethicone 0-40 0.01-40 caprylylmethicone 0-10 0.01-10 Dimethicone crosspolymer 0-90 0.01-90 C30-C45 alkyl cetearyl dimethicone crosspolymer Glycolic acid 0-10 0.01-10 KCI 0-5 0.01-5 Niacinamide 0-5 0.01-5 Perfume 0-2 0-2 Glutamine/Sodium pyrrolidone carbonate (ROA) 0.01-10 0.01-10 Glycine 0.01-10 0.01-10 cystine 0.001-2 0.001-2 4-G exylresorcinol 0.001-3 4-Ethylresorcinol 0.001-3 4-Butylresorcinol 4-(1-Phenylethyl)resorcinol

- 17 042158

Table III

Fast absorbing creams ___________

VC-2 VC-3 VC-4 Water Up to 100 Up to 100 Up to 100 Glycerol 0.01-5 0.01-5 EDTA 0.01-0.1 0.01-0.1 0.01-0.1 preservative 0.02-2 0.02-2 0.02-2 TU2 0.01-10 0.01-10 0.01-10 Dye/Pigment 0.01-5 0.01-5 TEA/sodium hydroxide/potassium hydroxide 0.01-3 0.01-3 0.01-3 Stearic acid 0.01-30 0.01-30 0.01-30 Isopropyl myristate 0.01-10 0.01-10 C12-C15 alkyl benzoate 0.01-10 Brij 35 0.01-5 Tween40 0.01-5 cetyl alcohol 0.01-2 0.01-2 Ethylhexylmethoxycinnamate 0.01-6 0.01-6 Butylmethoxydibenzoylmethane 0.01-3 0.01-3 0.01-3 Enzulizol 0.01-4 Octisalate 0.01-5 Octocrylene 0.01-10 0.01-10 Dimethicone 0.01-5 Cyclomethicone 0.01-5 Dimethicone crosspolymer 0.01-4 Hydroxystearic acid 0.01-5 0.01-5 0.01-5 Perfume 0-2 0-2 0-2 Glutamine/sodium pyrrolidone carboxylate (PCA) 0.01-10 0.01-10 0.01-10 Glycine 0.01-10 0.01-10 0.01-10 cystine 0.001-2 0.001-2 0.001-2 Nicotinamide 0.01 -5 0.01 -5 0.01 -5

CLAIM

Claims (11)

CLAIM 1. A method of obtaining a composition for personal hygiene, for topical use, including: a) stirring from 0.5 to 10 wt.% cystine in a basic aqueous solution at a pH of 9 to 14 to obtain an aqueous solution of cystine; b) mixing the obtained aqueous solution of cystine with a lamellar liquid crystalline or lamellar gel fatty acid-soap phase obtained by neutralizing a C ₁₀ -C ₂₂ fatty acid at 50-60°C to obtain a composition containing cystine in the aqueous phase in a solubilized form or in the form of crystals, where from 90 to 100% of the crystals have a size from 100 nm to 20 μm, where the pH of the specified composition is in the range from 3.5 to 8.5. - 18 042158 2. The method according to claim 1, characterized in that more than 30 wt.% of the composition is in the form of a lamellar liquid crystalline or lamellar gel phase. 3. Process according to any one of claims 1 or 2, characterized in that the mole ratio of fatty acid to soap is from 10:1 to 1:10. 4. A method according to any one of claims 1 to 3, characterized in that said fatty acid is a C1o-C22 saturated fatty acid. 5. The method according to any one of claims 1 to 3, characterized in that said fatty acid is a hystric acid. 6. The method according to any one of claims 1 to 4, characterized in that cystine is solubilized in an amount of from 150 to 1000 ppm. 7. Composition for personal care, for topical use, obtained by the method according to any one of claims 1 to 6, while the specified composition contains cystine in the aqueous phase in solubilized form or in the form of crystals, where from 90 to 100% of the crystals have a size of 100 nm to 20 μm, while cystine is solubilized in an amount from 150 to 1000 ppm, and the pH of this composition is in the range from 3.5 to 8.5. 8. The composition of claim 7, wherein said composition is a non-rinsing, non-solid skin cosmetic composition. 9. A composition according to any one of claims 7 or 8, wherein said composition is a fast absorbing cream containing 5 to 40 wt% fatty acid and 0.1 to 20 wt% soap. 10. A composition according to any one of claims 7 to 9, wherein said composition further comprises an amino acid selected from the group consisting of glutamine, glycine, and mixtures thereof. 11. A composition according to any one of claims 7 to 9, wherein said composition further comprises glutamic acid and/or pyroglutamic acid and/or salts thereof.