Cosmetic composition

Abstract: A non-aqueous drug-tree composition for topical application to human skin comprises: (i) a special ester of pyroglutamic acid; and (ii) a cosmetically acceptable non-aqueous vehicle.

Description: FIELD OF INVENTION The invention relates to non-aqueous compositions containing an ester of pyroglutamic acid for topical application to human skin to enhance the quality of the skin, or to the hair and/or scalp to promote hair growth. BACKGROUND AND PRIOR ART Pyroglutamic acid (also known as 2-pyrrolidone-5-carboxylic acid) is the principal ingredient of the "natural moisturising factor" that enables the stratum corneum of the skin to maintain a high water content despite low external humidity. Pyroglutamic acid applied topically to the skin has a temporary moisturising effect, but it is easily washed away and gives no long term skin benefit. The use of certain esters of pyroglutamic acid as auxiliary agents for accelerating absorption of drugs through the skin is described in JA 60-214744 (Nitto Denki Kogyo KK. FR-A-2 122 495 (Dr Karl Thomae) describes non-aqueous compositions containing pyroglutamic acid hexadecyl ester. The compositions are said to have several desirable properties when applied on the skin. These properties include inter alia anti-inflammatory and anti-dandruff efficacy as well as a moisturizing effect. Cosmetics containing one or more compounds obtained by the esterification of 2-pyrrolidone-5-carboxylic acid (PCA) and a fatty acid chosen from straight chain higher fatty acids are described in JA 57-185209 (Nisshin Seiyu KK) for contributing to the natural moisturising factor (NMF) present in the horny layer of the skin, part of which NMF is characterised as a salt of PCA. Certain esters of pyroglutamic acid described in EP-A-0 176 217 (Unilever) are stated to be analogues of naturally occuring N-terminal pyroglutamic peptides. These naturally ocurring peptides are substrates for the enzyme pyroglutamic acid peptidase which represent one route of pyroglutamic acid synthesis in the stratum corneum: [See: J G Barrett and I R Scott (1983), "Pyrrolidone carboxylic acid synthesis in guinea pig epidermis", J Invest. Dermatol. 81 , 122]. These esters are stated to penetrate readily into the stratum corneum, and there provide a substrate for this enzyme at the normal site of pyroglutamic acid synthesis, that is, inside the cells of the stratum corneum. There are, however, certain disadvantages in employing products based on these prior proposals; these are firstly, in aqueous systems, there is a tendency for hydrolysis of the ester of pyroglutamic acid to occur prematurely, so that the free acid, pyroglutamic acid, is present in the composition, and its benefit prior to application to the skin is thereby at best relatively short lived, and secondly, that the presence of drugs in topical products can severely limit their cosmetic usefulness. We have now discovered that the stability of esters of pyroglutamic acid can be significantly improved and the general cosmetic use widened, by formulating them in a non-aqueous composition (that is one in which the amount of water present does not exceed 5% by weight of the composition), which otherwise contains no molecule that could be classed as a drug, thereby limiting its cosmetic usefulness. Evidence in support of the preference for a non-aqueous composition to provide enhanced stability for the ester, compared with compositions containing >5% water, is given later in this specification. We have, furthermore, found that the ester of pyroglutamic acid penetrates more readily into the stratum corneum than does the free acid, the penetrated ester being enzymically cleaved, as already stated, to yield pyroglutamic acid in situ in the stratum corneum, thereby to augment that which occurs naturally in this region of the skin. Evidence to support this observation is give later in this specification. DEFINITION OF THE INVENTION Accordingly, the invention provides a non-aqueous composition for topical application to human skin which comprises: (i) from 0.01 to 99% by weight of an ester of pyroglutamic acid having the structure: wherein R is a linear C₁₋₆ alkyl group; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle, "non-aqueous" signifying not more than 5% by weight of water in the composition. The invention also provides the use for inducing maintaining or increasing hair growth of a non-aqueous drug-free composition which comprises (i) from 0.1 to 20% by weight of an ester of pyroglutamic acid having the structure where R is a linear or branched chain saturated or unsaturated alkyl group having from 1 to 30 carbon atoms, or the group: where R' and R'' are the same or different and are each represented by H or the group; [(CH₃) u' (CH₂OH) v' (CH₂) w' (CHCH₃) x' (CHOH) y' (CH=CH) z ]- (2) where one of u and v is zero and the other is 1 w is zero, or an integer of from 1 to 21 x is zero, or an integer of from 1 to 4 y is zero, or an integer of from 1 to 2 z is zero, or an integer of from 1 to 4; and u + v + w + x + y + z is an integer of from 1 to 22; the subgroups within the group (2) being in any sequence; provided that when the subgroup (CH=CH) is present, then the total number of carbon atoms in said group (2) will be from 10 to 20; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle. DISCLOSURE OF THE INVENTION It is accordingly an object of the invention to provide a non-aqueous composition which is suitable for topical application to human skin, including the lips and mucosae, the composition comprising certain esters of pyroglutamic acid in a non-aqueous vehicle, to provide a source of pyroglutamic acid to the skin, in particular to the stratum corneum, following topical application. It is also an object of the invention to provide a non-aqueous composition, of a similar nature, suitable for topical application to the hair and/or scalp in order to induce, maintain or increase hair growth. By "non-aqueous" is meant that the composition according to the invention will contain no more than 5% by weight of water. Preferably, the composition will contain no more that 3%, most preferably no more than 2% by weight of water. The esters of pyroglutamic acid Examples of suitable esters of pyroglutamic acid for the use aspect where R in structure (1) is a C₁ to C₃₀ linear or branched chain alkyl group are: pyroglutamic acid methyl ester pyroglutamic acid ethyl ester pyroglutamic acid n-propyl ester pyroglutamic acid n-butyl ester pyroglutamic acid n-hexyl ester pyroglutamic acid n-heptyl ester pyroglutamic acid n-octyl ester pyroglutamic acid n-nonyl ester pyroglutamic acid n-decyl ester pyroglutamic acid n-undecyl ester pyroglutamic acid n-dodecyl ester pyroglutamic acid n-tridecyl ester pyroglutamic acid n-tetradecyl ester pyroglutamic acid n-hexadecyl ester pyroglutamic acid n-octadecyl ester pyroglutamic acid n-eicosyl ester pyroglutamic acid iso-propyl ester pyroglutamic acid 2-methylhexyl ester pyroglutamic acid 2-ethylhexyl ester pyroglutamic acid 3,7-dimethyloctyl ester pyroglutamic acid 2-hexyldecyl ester pyroglutamic acid 2-octyldodecyl ester pyroglutamic acid 2,4,4-trimethyl-1-pentane ester pyroglutamic acid methyloctyl ester. Particularly preferred esters of this group are those where R in structure (1) is C₁ to C₁₄ alkyl, (linear or branched), especially C₁ to C₆ alkyl (linear or branched). Where R is C₁₋₆ linear alkyl, non-aqueous compositions per se are claimed. Examples of the group (2) include straight and branched chain, saturated or unsaturated aliphatic groups having from 1 to 22 carbon atoms, such as the alkyl groups: methyl ethyl propyl iso-propyl butyl iso-butyl n-valeryl iso-valeryl n-caproyl n-heptyl n-caprylyl n-capryl lauryl myristyl palmityl stearyl arachidyl, and behenyl; and the C₁₀₋₂₂ alkenyl groups: linoleyl linolenyl γ-linolenyl arachidonyl, and columbinyl. Examples of the group (2) also include hydroxyalkyl groups having from 1 to 22 carbon atoms, such as: hydroxymethyl 2-hydroxyethyl 2-hydroxy-n-propyl 3-hydroxy-n-propyl 2-hydroxy-n-butyl 3-hydroxy-n-butyl 4-hydroxy-n-butyl 5-hydroxy-n-valeryl 6-hydroxy-n-caproyl 2,3-dihydroxy-n-propyl 2,3-dihydroxy-n-butyl 12-hydroxystearyl. Further specific examples of esters of pyroglutamic acid containing the group: are: 2-[pyroglutamoyloxy]-propionic acid methyl-2-[pyroglutamoyloxy]-acetate ethyl-2-[pyroglutamoyloxy]-n-propionate ethyl-2-[pyroglutamoyloxy]-n-butyrate ethyl-2-[pyroglutamoyloxy]-iso-butyrate ethyl-2-[pyroglutamoyloxy]-n-valerate ethyl-2-[pyroglutamoyloxy]-n-caproate ethyl-2-[pyroglutamoyloxy]-n-heptylate ethyl-2-[pyroglutamoyloxy]-n-caprylate ethyl-2-[pyroglutamoyloxy]-n-pelargonate ethyl-2-[pyroglutamoyloxy]-3-hydroxybutyrate iso-propyl-2-[pyroglutamoyloxy]-n-propionate iso-propyl-2-[pyroglutamoyloxy]-n-caprylate n-propyl-2-[pyroglutamoyloxy]-n-propionate n-propyl-2-[pyroglutamoyloxy]-n-caprylate stearyl-2-[pyroglutamoyloxy]-n-propionate 12-hydroxystearyl-2-[pyroglutamoyloxy]-n-propionate stearyl-2-[pyroglutamoyloxy]-n-stearate palmityl-2-[pyroglutamoyloxy]-n-propionate linoleyl-2-[pyroglutamoyloxy]-n-propionate linoleyl-2-[pyroglutamoyloxy]-n-caprylate lauryl-2-[pyroglutamoyloxy]-n-caprylate stearyl-2-[pyroglutamoyloxy]-n-caprylate glyceryl mono(2-[pyroglutamoyloxy]-n-propionate) glyceryl mono(2-[pyroglutamoyloxy]-n-caprylate), and glyceryl di(2-[pyroglutamoyloxy]-n-propionate). It is to be understood that the above list of specific examples of esters of pyroglutamic acid is not exhaustive, there being many other examples expressed by the generic structure of these esters. The amount of the esters of pyroglutamic acid or mixtures thereof to be employed, will normally be from 0.01 to 99%, preferably from 0.01 to 20% and most preferably from 0.2 to 2% by weight of the composition. The Non-Aqueous Vehicle The composition also comprises a solid, semi-solid or liquid cosmetically and/or physiologically acceptable non-aqueous vehicle, to enable the ester to be conveyed to the skin or hair at an appropriate dilution. The nature of the vehicle will depend upon the method chosen for topical administration of the composition. The selection of a vehicle for this purpose presents a wide range of possibilities depending on the required product form of the composition. Suitable vehicles can be classified as described hereinafter. It should be explained that vehicles are substances which can act as diluents, dispersants, or solvents for the esters which therefore ensure that they can be applied to and distributed evenly over the skin or hair at an appropriate concentration. The vehicle is preferably one which can aid penetration of the ester into the skin to reach the stratum corneum. Non-aqueous vehicles that can be used include solids or liquids such as emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicles, which can be used singly or as mixtures of one or more vehicles, are as follows: Emollients, such as stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane-1,2-diol, butane-1,3-diol, mink oil, cetyl alcohol, ispropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, dimethylpolysiloxane, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polythylene glycol, triethylene glycol, lanolin, sesame oil, coconut oil, arachis oil, sunflower seed oil, evening primrose oil, castor oil, lanolin alcohols, petrolatum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate; Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorotrifluoroethane, propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide; Solvents, such as ethyl alcohol, methylene chloride, isopropanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, dimethyl formamide, tetrahydrofuran; Humectants, such as glycerin, sorbitol, sodium 2-pyrrolidone-5-carboxylate, soluble collagen, dibutyl phthalate, gelatin; Gelling agents such as soaps and fatty alcohols; Powders, such as chalk, talc, fullers earth, kaolin, starch, gums, colloidal silicon dioxide, sodium polyacrylate, tetra alkyl and/or trialkyl aryl ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate. The amount of non-aqueous vehicle in the composition, can comprise the balance of the composition, particularly where little or no other ingredients are present in the composition. Accordingly, the vehicle or vehicles can comprise from 1 to 99.99%, preferably from 50 to 99.5% and ideally from 90 to 99% by weight of the composition. Perfume The composition can also optionally comprise a perfume in an amount sufficient to make the composition acceptable to the consumer and pleasant to use. Usually, the perfume when present will form from 0.01 to 10% by weight of the composition. Activity Enhancer The composition can also optionally comprise an activity enhancer, which can be chosen from a wide variety of molecules that can function in different ways to enhance delivery to the stratum corneum, of the ester or to potentiate its activity. Particular classes of activity enhancers include penetration enhancers and cationic polymers. Penetration Enhancers As has been stated earlier, the presence of a penetration enhancer can potentiate the benefit of the ester of pyroglutamic acid, by improving its delivery to the stratum corneum. The penetration enhancer can accordingly function in a variety of ways. It can for example, improve the distribution of the ester on the skin surface or, it can increase its partition into the skin from the composition when applied topically, so aiding its passage to its site of action. Other mechanisms enhancing the benefit of the chemical inhibitor may also be involved. Examples of penetration enhancers include: 2-methyl propan-2-ol Propan-2-ol Ethyl-2-hydroxypropanoate Hexan-2,5-diol POE(2) ethyl ether Di(2-hydroxypropyl) ether Pentan-2,4-diol Acetone POE(2) methyl ether 2-hydroxypropionic acid 2-hydroxyoctanoic acid Propan-1-ol 1,4 Dioxane Tetrahydrofuran Butan-1,4-diol Propylene glycol dipelargonate Polyoxypropylene 15 stearyl ether Octyl alcohol POE ester of oleyl alcohol Oleyl alcohol Lauryl alcohol Dioctyl adipate Dicapryl adipate Diisopropyl adipate Diisopropyl sebacate Dibutyl sebacate Diethyl sebacate Dimethyl sebacate Dioctyl sebacate Dibutyl suberate Dioctyl azelate Debenzyl sebacate Dibutyl phthalate Dibutyl azelate Ethyl myristate Dimethyl azelate Butyl myristate Dibutyl succinate Didecyl phthalate Decyl oleate Ethyl caproate Ethyl salicylate Isopropyl palmitate Ethyl laurate 2-ethyl-hexyl pelargonate Isopropyl isostearate Butyl laurate Benzyl benzoate Butyl benzoate Hexyl laurate Ethyl caprate Ethyl caprylate Butyl stearate Benzyl salicylate 2-hydroxypropanoic acid 2-hyroxyoctanoic acid, Further examples of penetration enhancers include:- Dimethyl sulphoxide N,N-Dimethyl acetamide N,N-Dimethyl formamide 2-Pyrrolidone 1-Methyl-2-pyrrolidone 5-Methyl-2-pyrrolidone 1,5-Dimethyl-2-pyrrolidone 1-Ethyl-2-pyrrolidone Phosphine oxides Sugar esters Tetrahydrofurfural alcohol Urea Diethyl-m-toluamide, and 1-Dodecylazacyloheptan-2-one Further examples of penetration enhancers include surface active agents, preferred examples of which include: (i) Anionic surface active agents, such as metallic or alkanolamine salts of fatty acids for example sodium laurate and triethanolamine oleate; alkyl benzene sulphonates, for example triethanolamine dodecyl benzene sulphonate; alkyl sulphates, for example sodium lauryl sulphate; alkyl ether sulphates, for example sodium lauryl ether sulphate [2 to 8 EO]; sulphosuccinates, for example sodium dioctyl sulphonsuccinate; monoglyceride sulphates, for example sodium glyceryl monostearate monosulphate; isethionates, for example sodium isethionate; methyl taurides, for example Igepon T; acylsarcosinates, for example sodium myristyl sarcosinate; acyl peptides, for example Maypons and Lamepons; acyl lactylates, polyalkoxylated ether glycollates, for example trideceth-7 carboxylic acid; phosphates, for example sodium dilauryl phosphate. (ii) Cationic surface active agents, such as amine salts, for example sapamin hydrochloride; quaternary ammonium salts, for example Quaternium 5, Quaternium 31 and Quaternium 18; (iii) Amphoteric suface active agents, such as imidazol compounds, for example Miranol; N-alkyl amino acids, such as sodium cocaminopropionate and asparagine derivatives; betaines, for example cocoamidopropylbetaine (iv) Nonionic surface active agents, such as fatty acid alkanolamides, for example oleic ethanolamide; esters of polyalcohols, for example Span; polyglycerol esters, for example that esterified with C₁₂₋₁₈ fatty acids and one or several OH groups; polyalkoxylated derivatives, for example polyoxy:polyoxyethylene stearate, and octylphenoxy polyethoxyethanol (TRITON X-100); ethers, for example polyoxyethylene lauryl ether; ester ethers, for example Tween; amine oxides, for example coconut and dodecyl dimethyl amine oxides. Mixtures of two or more of the above surface active agents can be employed in the composition. (c) cationic polymers chosen from: Guar Hydroxypropyltrimonium chloride Quaternium-19 Quaternium-23 Quaternium-40 Quaternium-57 Poly(dipropyldiallylammonium chloride) Poly(methyl-β-propaniodiallylammonium chloride) Poly(diallylpiperidinium chloride) Poly(vinyl pyridinium chloride) Quaternised poly (vinyl alcohol) Quaternised poly (dimethylaminoethylmethacrylate); and mixtures thereof The amount of activity enhancer, when employed in accordance with the invention, will normally be from 0.1 to 50%, preferably from 0.5 to 25% and most preferably from 0.5 to 10% by weight of the composition. FURTHER OPTIONAL INGREDIENTS The composition can also optionally contain further ingredients in addition to those which are conventionally used for the provision of the non-aqueous cosmetics acceptable vehicle. Accordingly, in addition to ingredients conventionally used in preparing a non-aqueous lotion, ointment, gel, powder, solid stick and aerosol concentrate, the composition can optionally comprise further ingredients such as a colourant, preservative, antioxidant, emollient or aerosol propellant, in amounts which are conventional in the cosmetics art. PREPARATION OF THE COMPOSITION The composition can be prepared in the form of a solution, lotion, gel, ointment, solid stick, aerosol or powder, or in any other form suited to administration topically to human skin and hair. When the composition is a liquid, such as a lotion or aerosol, or a semi-liquid such as a gel or ointment, or a solid stick, then it is usually necessary to dissolve an effective quantity of the ester of pyroglutamic acid, or a mixture thereof, in ethanol or other non-aqueous cosmetically acceptable vehicles, and then to admix this solution, if desired, in a conventional manner with a suitable ointment base containing, for example an oil or silicone oil, or stick base containing a gelling agent such as sodium stearate, or with a normally liquefiable gaseous propellant in order to prepare the composition. When the composition is a powder, then it is usually necessary to admix the ester of pyroglutamic acid or a mixture thereof, with a powder diluent, such as talc, starch, kaolin, Fuller's earth or other suitable powder base, in order to provide the composition in powder form. If desired, other cosmetically acceptable carriers, diluents or emollients can be incorporated in the composition according to the invention, in order to facilitate even distribution over the skin or hair at a suitable concentration. Evidence to support benefit of topical application to skin of the ester of pyroglutamic acid versus the free acid, with particular reference to the preference for employing a non-aqueous vehicle When pyroglutamic acid is applied topically to human skin, only a negligible amount is able to penetrate to the stratum corneum to augment that naturally present in this region of the skin. However, certain esters of pyroglutamic acid are able readily to penetrate the skin to reach the stratum corneum, where naturally occuring esterases cleave the ester to yield the free pyroglutamic acid which can then augment that which is naturally present in the skin, with the consequence that skin benefit is improved. Delivery of esters of pyroglutamic acid, with subsequent hydrolysis to yield free pyroglutamic acid in the stratum corneum, was confirmed using tritiated esters of pyroglutamic acid and a radio-tracer technique. Accordingly, [³H] esters of pyroglutamic acid were each dissolved at 1% w/v in anhydrous ethanol or in an oil-in-water emulsion base containing >5% by weight of water. These solutions were then applied to the arms of volunteers, left for 18 hours, washed with soap and water, and the stratum corneum was removed by stripping with Sellotape. The [³H] pyroglutamic acid was separated from unchanged ester by chromotography on AG1X8 resin and the amount delivered to the skin expressed as nmoles per mg of stratum corneum protein. The result obtained are summarised in Table 1: Ester of Pyroglutamic acid Pyroglutamic acid delivered (n mol/mg protein) Ethanol base Cream base Ethyl 8 5 Butyl 6 2 Hexyl 5 2 Octyl 4 1 Dodecyl 4 1 When [³H] pyroglutamic acid instead of a corresponding ester was applied topically in this experiment, a negligible amount of the tritiated free acid was recovered from the stratum corneum. The above results indicate that pyroglutamic acid is effectively delivered to the stratum corneum following topical application of an ester thereof, while little pyroglutamic acid reached the stratum corneum if applied as the free acid. These results also indicate a preference for a non-aqueous composition, rather than an aqueous cream base. Also, the shorter the alkyl chain of the ester, the more effective is the delivery of the ester to the stratum corneum, as judged by the higher yield of pyroglutamic acid found in that region of the skin. EVALUATION OF EFFICACY OF ESTERS OF PYROGLUTAMIC ACID AS HAIR GROWTH PROMOTERS USING THE RAT MODEL The Rat Hair Growth Test The effect of compounds on hair growth was assessed using male albino Wistar rats as an animal model. The rats were chosen from as few litters as possible and were each approximately 42 days of age at the start of the test. Each rat was housed individually to prevent licking. In each comparison, 10 rats were used in each group and hair growth was assessed as follows: A small patch of normal skin (4cm x 4cm) on the upper back of each rat was clipped at the start and 0.3 ml of a hair growth stimulant composition (or a control) applied topically twice daily and once on Saturdays and Sundays to each clipped area. The concentration of test compound in the composition was chosen from 0.1 to 20% by weight. It is to be understood that the potency of each of the esters of pyroglutamic acid in terms of its ability to induce, maintain or increase hair growth is unlikely to be uniform, some being more potent than others, and therefore the concentration of any ester chosen for thorough evaluation must be carefully selected after preliminary testing to determine its potential as a hair growth promoter. In any case, this concentration will lie within the range of from 0.1 to 20% by weight as stipulated above. Hair was clipped from the area of the patch twice weekly, collected and weighed at each time point over a standard period of 3 months, and cumulative hair weight calculated. From these data, it was possible to estimate the effect of an ester of pyroglutamic acid as a hair growth stimulant (test compound) on the amount and duration of hair growth during the experiment. A positive response, i.e. an increase of at least 10% by weight of hair after 3 months treatment, compared with a control indicates the potential of the test compound to prevent hair loss and/or reverse baldness in human subjects. Accordingly, when the esters, as herein defined, are assessed either individually or in combination as test compound by the Rat Hair Growth Test, an increase of at least 10% by weight of hair after 3 months treatment will be obtained. Usually, the 10% by weight minimum value will be attained well before the end of this 3 months period. Examples The invention is further illustrated by the following examples. Example 1. Suntan Oil Ingredient % by wt. Phase A propylene glycol myristyl ether 22.0 cetyl palmitate 22.0 2-ethylhexyl methoxycinnamate 5.0 pyroglutamic acid n-hexyl ester 5.0 fragrance 0.1 Phase B glyceryl sterate 22.0 mineral oil 23.9 In a vessel, mix in components of Phase A, in order, until all items are dissolved. Upon completion of Phase A, add components in Phase B to those is Phase A and continue mixing until uniform. Example 2. Suntan Oil Ingredient % by wt. Phase A PPG-1 myristyl ether acetate 22.0 Cetyl palmitate 22.0 Parsol MCX 8.0 Benzophenone - 3 4.0 ethyl -2-[pyroglutamoyloxy]-n-propionate 1.0 Fragrance 0.1 Phase B Glyceryl triacetyl hydroxystearate 22.0 PPG-3 hydrogenated castor oil 20.9 In a vessel, mix in components of Phase A, in order, until all items are dissolved. Upon completion of Phase A, add components in Phase B to those in Phase A and continue mixing until uniform. Example 3. Dry Skin Cream Ingredient % by wt petrolatum, white USP 49.9 polyethylene 3.0 silicone dioxide 2.0 cyclomethicone 33.8 dimethicone, 50cs 10.0 mineral oil 1.0 propylparaben 0.1 sorbic acid 0.1 fragrance 0.1 pyroglutamic acid ethyl ester 1.0 Add petrolatum, polyethylene and silicone dioxide to a vessel, heat to 80°C, and homogenize. To this mixture add cyclomethicone, dimethicone, mineral oil, propylparaben and sorbic acid, dissolve and blend, and then cool to 35°C. Dissolve into this mixture PCA ester, and blend until a uniform dry skin composition containing solubilized PCA ester is obtained. Example 4. Dry Skin Lip Balm Ingredient % by wt triglycerides 17.0 trilaurin 36.7 mineral oil 9.0 beeswax 11.0 paraffin 12.0 petrolatum 13.0 fragrance/flavour 0.3 pyroglutamic acid octyl ester 1.0 Example 5. Lip Balm Ingredient % by wt petrolatum 51.0 cetyl ester 9.0 cetyl alcohol 13.0 oleyl alcohol 8.0 beeswax 8.0 mineral oil 6.0 pyroglutamic acid butyl ester 5.0 Example 6. HAIR GROWTH FORMULATION The following example illustrates a non-aqueous lotion according to the invention which can be applied topically to the scalp to prevent hair loss and stimulate hair regrowth. Ingredient % w/w L-Pyroglutamic acid hexyl ester 1 perfume q.s. ethanol to 100

Claims: Claims for the following Contracting States : AT, BE, CH, LI, DE, FR, GB, GR, IT, NL, SE A non-aqueous composition for topical application to human skin or hair which comprises: (i) from 0.01 to 99% by weight of an ester of pyroglutamic acid having the structure: where R is a linear C₁ to C₆ alkyl group; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle, "non-aqueous" meaning that there is not more than 5% by weight water in the composition. Composition according to claim 1 in which the non-aqueous vehicle is chosen from petrolatum, lanolin, lanolin alcohols, mineral oil, sunflower seed oil, evening primrose oil, sesame oil, ethyl alcohol, glycerin, and mixtures thereof. Composition according to claim 1, wherein the composition additionally comprises from 0.01 to 10% by weight of a perfume. Composition according to claim 1, wherein the composition further comprises an activity enhancer. Composition according to claim 4, in which the activity enhancer is chosen from penetration enhancers, surface active agents and cationic polymers. Composition according to claim 4 or claim 5, in which the activity enhancer forms from 0.1 to 50% by weight of the composition. Use for inducing, maintaining or increasing hair growth of a non-aqueous composition which comprises: (i) from 0.01 to 20% by weight of an ester of pyroglutamic acid having the structure: where R is a linear or branched chain saturated or unsaturated alkyl group having from 1 to 30 carbon atoms, or the group: where R' and R'' are the same or different and are each represented by H or the group: [(CH₃) u' (CH₂OH) v' (CH₂) w' (CHCH₃) x' (CHOH) y' (CH=CH) z ]- (2) where one of u and v is zero and the other is 1 w is zero, or an integer of from 1 to 21 x is zero, or an integer of from 1 to 4 y is zero, or an integer of from 1 to 2 z is zero, or an integer of from 1 to 4; and u + v + w + x + y + z is an integer of from 1 to 22; the subgroups within the group (2) being in any sequence; provided that when the subgroup (CH=CH) is present, then the total number of carbon atoms in said group (2) will be from 10 to 20; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle, "non-aqueous" meaning that there is not more than 5% by weight water in the composition. Use according to claim 7, in which the ester of pyroglutamic acid is chosen from those where R in structure (1) is a C₁ to C₃₀ linear or branched chain alkyl group. Use according to claim 8, in which the ester of pyroglutamic acid is chosen from: pyroglutamic acid methyl ester pyroglutamic acid ethyl ester pyroglutamic acid n-propyl ester pyroglutamic acid n-butyl ester pyroglutamic acid n-hexyl ester pyroglutamic acid n-heptyl ester pyroglutamic acid n-octyl ester pyroglutamic acid n-nonyl ester pyroglutamic acid n-decyl ester pyroglutamic acid n-undecyl ester pyroglutamic acid n-dodecyl ester pyroglutamic acid n-tridecyl ester pyroglutamic acid n-tetradecyl ester pyroglutamic acid n-hexadecyl ester pyroglutamic acid n-octadecyl ester pyroglutamic acid n-eicosyl ester pyroglutamic acid iso-propyl ester pyroglutamic acid 2-methylhexyl ester pyroglutamic acid 2-ethylhexyl ester pyroglutamic acid 3,7-dimethyloctyl ester pyroglutamic acid 2-hexyldecyl ester pyroglutamic acid 2-octyldodecyl ester pyroglutamic acid 2,4,4-trimethyl-1-pentane ester pyroglutamic acid methyloctyl ester Use according to claim 7 , in which the R group in structure (1) is the group as defined in claim 7. Use according to claim 10, in which the group (2) is chosen from straight or branched chain, saturated or unsaturated aliphatic groups having from 1 to 22 carbon atoms or from alkenyl groups having from 10 to 22 carbon atoms. Use according to claim 7, 10 or 11 in which the ester of pyroglutamic acid is chosen from 2-(Pyroglutamoyloxy)-propionic acid methyl-2(pyroglutamoyloxy)-acetate ethyl-2-(pyroglutamoyloxy)-n-propionate ethyl-2-(pyroglutamoyloxy)-n-butyrate ethyl-2-(pyroglutamoyloxy)-iso-butyrate ethyl-2-(pyroglutamoyloxy)-n-valerate ethyl-2-(pyroglutamoyloxyl)-n-caproate ethyl-2-(pyroglutamoyloxyl)-n-heptylate ethyl-2-(pyroglutamoyloxy)-n-caprylate ethyl-2-(pyroglutamoyloxy)-n-pelargonate ethyl-2-(pyroglutamoyloxy)-3-hydroxybutyrate iso-propyl-2-(pyroglutamoyloxy)-n-propionate iso-propyl-2-(pyroglutamoyloxy)-n-caprylate n-propyl-2-(pyroglutamoyloxy)-n-propionate n-propyl-2-(pyroglutamoyloxy)-n-caprylate stearyl-2-(pyroglutamoyloxy)-n-propionate 12-hydroxystearyl-2-(pyroglutamoyloxy)-n-propionate stearyl-2-(pyroglutamoyloxy)-n-stearate palmityl-2-(pyroglutamoyloxy)-n-propionate linoleyl-2-(pyroglutamoyloxy)-n-propionate linoleyl-2-(pyroglutamoyloxy)-n-caprylate lauryl-2-(pyroglutamoyloxy)-n-caprylate stearyl-2-(pyroglutamoyloxy)-n-caprylate glyceryl mono(2-(Pyroglutamoyloxy)-n-propionate glyceryl mono(2-(pyroglutamoyloxy)-n-caprylate), and glyceryl di(2-(Pyroglutamoyloxy)-n-propionate. Use according to any one of claims 7 to 12, in which the non-aqueous vehicle is chosen from petrolatum, lanolin, lanolin alcohols, mineral oil, sunflower seed oil, evening primrose oil, sesame oil, ethyl alcohol, glycerin, and mixtures thereof. Use according to any one of claims 7 to 12, wherein the composition additionally comprises from 0.01 to 10% by weight of a perfume. Use according to any one of claims 7 to 12, wherein the composition further comprises an activity enhancer. Use according to claim 15, in which the activity enhancer is chosen from penetration enhancers, surface active agents and cationic polymers. Use according to claim 15 or claim 16, in which the activity enhancer forms from 0.1 to 50% by weight of the composition. Use according to claim 7, in which the ester of pyroglutamic acid is chosen from those where R in structure (1) is a C₂ to C₁₂ alkyl group. Use according to claim 18, in which the ester of pyroglutamic acid is chosen from: pyroglutamic acid n-butyl ester pyroglutamic acid n-pentyl ester pyroglutamic acid n-hexyl ester pyroglutamic acid n-heptyl ester, and pyroglutamic acid n-octyl ester. Claims for the following Contracting State : ES A non-aqueous composition for topical application to human skin or hair which comprises: (i) from 0.01 to 99% by weight of an ester of pyroglutamic acid having the structure: where R is a linear C₁ to C₆ alkyl group; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle, "non-aqueous" meaning that there is not more than 5% by weight water in the composition. Composition according to claim 1 in which the non-aqueous vehicle is chosen from petrolatum, lanolin, lanolin alcohols, mineral oil, sunflower seed oil, evening primrose oil, sesame oil, ethyl alcohol, glycerin, and mixtures thereof. Composition according to claim 1, wherein the composition additionally comprises from 0.01 to 10% by weight of a perfume. Composition according to claim 1, wherein the composition further comprises an activity enhancer. Composition according to claim 4, in which the activity enhancer is chosen from penetration enhancers, surface active agents and cationic polymers. Composition according to claim 4 or claim 5, in which the activity enhancer forms from 0.1 to 50% by weight of the composition. Use for inducing, maintaining or increasing hair growth of a non-aqueous composition which comprises: (i) from 0.01 to 20% by weight of an ester of pyroglutamic acid having the structure: where R is a linear or branched chain saturated or unsaturated alkyl group having from 1 to 30 carbon atoms, or the group: where R' and R'' are the same or different and are each represented by H or the group: [(CH₃) u' (CH₂OH) v' (CH₂) w' (CHCH₃) x' (CHOH) y' (CH=CH) z ]- (2) where one of u and v is zero and the other is 1 w is zero, or an integer of from 1 to 21 x is zero, or an integer of from 1 to 4 y is zero, or an integer of from 1 to 2 z is zero, or an integer of from 1 to 4; and u + v + w + x + y + z is an integer of from 1 to 22; the subgroups within the group (2) being in any sequence; provided that when the subgroup (CH=CH) is present, then the total number of carbon atoms in said group (2) will be from 10 to 20; without any drug in addition to said ester and (ii) from 1 to 99.99% by weight of a cosmetically acceptable non-aqueous vehicle, "non-aqueous" meaning that there is not more than 5% by weight water in the composition. Use according to claim 7, in which the ester of pyroglutamic acid is chosen from those where R in structure (1) is a C₁ to C₃₀ linear or branched chain alkyl group. Use according to claim 8, in which the ester of pyroglutamic acid is chosen from: pyroglutamic acid methyl ester pyroglutamic acid ethyl ester pyroglutamic acid n-propyl ester pyroglutamic acid n-butyl ester pyroglutamic acid n-hexyl ester pyroglutamic acid n-heptyl ester pyroglutamic acid n-octyl ester pyroglutamic acid n-nonyl ester pyroglutamic acid n-decyl ester pyroglutamic acid n-undecyl ester pyroglutamic acid n-dodecyl ester pyroglutamic acid n-tridecyl ester pyroglutamic acid n-tetradecyl ester pyroglutamic acid n-hexadecyl ester pyroglutamic acid n-octadecyl ester pyroglutamic acid n-eicosyl ester pyroglutamic acid iso-propyl ester pyroglutamic acid 2-methylhexyl ester pyroglutamic acid 2-ethylhexyl ester pyroglutamic acid 3,7-dimethyloctyl ester pyroglutamic acid 2-hexyldecyl ester pyroglutamic acid 2-octyldodecyl ester pyroglutamic acid 2,4,4-trimethyl-1-pentane ester pyroglutamic acid methyloctyl ester Use according to claim 7, in which the R group in structure (1) is the group as defined in claim 7. Use according to claim 10, in which the group (2) is chosen from straight or branched chain, saturated or unsaturated aliphatic groups having from 1 to 22 carbon atoms or from alkenyl groups having from 10 to 22 carbon atoms. Use according to claim 7, 10 or 11 in which the ester of pyroglutamic acid is chosen from 2-(pyroglutamoyloxy)-propionic acid methyl-2(pyroglutamoyloxy)-acetate ethyl-2-(pyroglutamoyloxy)-n-propionate ethyl-2-(pyroglutamoyloxy)-n-butyrate ethyl-2-(pyroglutamoyloxy)-iso-butyrate ethyl-2-(pyroglutamoyloxy)-n-valerate ethyl-2-(pyroglutamoyloxyl)-n-caproate ethyl-2-(pyroglutamoyloxyl)-n-heptylate ethyl-2-(pyroglutamoyloxy)-n-caprylate ethyl-2-(pyroglutamoyloxy)-n-pelargonate ethyl-2-(pyroglutamoyloxy)-3-hydroxybutyrate iso-propyl-2-(pyroglutamoyloxy)-n-propionate iso-propyl-2-(pyroglutamoyloxy)-n-caprylate n-propyl-2-(pyroglutamoyloxy)-n-propionate n-propyl-2-(pyroglutamoyloxy)-n-caprylate stearyl-2-(pyroglutamoyloxy)-n-propionate 12-hydroxystearyl-2-(pyroglutamoyloxy)-n-propionate stearyl-2-(pyroglutamoyloxy)-n-stearate palmityl-2-(pyroglutamoyloxy)-n-propionate linoleyl-2-(pyroglutamoyloxy)-n-propionate linoleyl-2-(pyroglutamoyloxy)-n-caprylate lauryl-2-(pyroglutamoyloxy)-n-caprylate stearyl-2-(pyroglutamoyloxy)-n-caprylate glyceryl mono(2-(pyroglutamoyloxy)-n-propionate glyceryl mono(2-(pyroglutamoyloxy)-n-caprylate), and glyceryl di(2-(pyroglutamoyloxy)-n-propionate. Use according to any one of claims 7 to 12, in which the non-aqueous vehicle is chosen from petrolatum, lanolin, lanolin alcohols, mineral oil, sunflower seed oil, evening primrose oil, sesame oil, ethyl alcohol, glycerin, and mixtures thereof. Use according to any one of claims 7 to 12, wherein the composition additionally comprises from 0.01 to 10% by weight of a perfume. Use according to any one of claims 7 to 12, wherein the composition further comprises an activity enhancer. Use according to claim 15, in which the activity enhancer is chosen from penetration enhancers, surface active agents and cationic polymers. Use according to claim 15 or claim 16, in which the activity enhancer forms from 0.1 to 50% by weight of the composition. Use according to claim 7, in which the ester of pyroglutamic acid is chosen from those where R in structure (1) is a C₂ to C₁₂ alkyl group. Use according to claim 18, in which the ester of pyroglutamic acid is chosen from: pyroglutamic acid n-butyl ester pyroglutamic acid n-pentyl ester pyroglutamic acid n-hexyl ester pyroglutamic acid n-heptyl ester, and pyroglutamic acid n-octyl ester. A method of making a non-aqueous composition for topical application to human skin or hair which comprises admixing. (i) from 0.01 to 99% by weight of an ester of pyroglutamic acid having the structure: where R is a linear C₁ to C₆ alkyl group; without any drug in addition to said ester with (ii) from 1 to 99.99% by weight of a cosmetically acceptable non aqueous vehicle, "non-aqueous" meaning that there is not more than 5% by weight water in the composition.

Inventors: SCOTT IAN RICHARD, SCOTT, IAN RICHARD
Applicants: UNILEVER NV, UNILEVER PLC, UNILEVER N.V.
Application year: 1989
Main classification: A61K7
IPC codes: A61Q7, A61Q1, A61Q19, A61K8, A61Q5, A61K31