COSMETIC COMPOSITION

Abstract: Modified ceramides are defined, together with their synthesis and compositions comprising them for topical application to human skin, hair and nails. The modified pseudoceramides have structure (1) and an approximate summary is that R and R<1> are aliphatic hydrocarbon, A is CH2, CHOR<2>, CH=CH or CHOY, and at least one of R<2>, R<3> and R<4> is sulphate, phosphate or similar. The presence of phosphate or sulphate facilitates skin absorption, after which the phosphate or sulphate is removed by enzymes present in vivo.

Description: - 1 - COSMETIC COMPOSITION FIELD OF THE INVENTION The invention relates to modified ceramides, their synthesis and use in compositions for topical application to human skin, hair or nails. BACKGROUND TO THE INVENTION AND PRIOR ART It is generally understood that ceramides present within the intercellular lipid lamellae of the stratum corneum play an important role in the production and maintenance of the water permeability barrier of the skin. Ceramides, or substances closely related to them, have been disclosed as components of skin care compositions. In particular, Kao Corporation in GB 2178312 and GB 2 213 723 disclose the use of natural ceramides extracted from skin in topical products. Also, Unilever in EP 97 059 disclose -linoleoyl ceramides and emphasize their role in the water barrier function of the skin. It is believed that one of the causes of dry skin and ageing skin is a reduction in the amount of lipid contained within these intercellular lipid lamellae. It is therefore desirable to be able successfully to replace these depleted lipids via the topical route. One of the problems associated with the topical application of skin and hair care products containing ceramides or their synthetic analogues, is devising a suitable method for delivering them effectively to the lipid lamellae, without causing permanent disruption of the stratum corneum. It is accordingly apparent that permanently disrupted stratum corneum is unable to retain molecules of this sort, as they are simply washed out again when the stratum corneum (skin) is contacted with water. This problem has not_successfully been solved to date. Kao Corporation have reported in GB 2 178 312, EP 227 994 and EP 282 816, that co-surfactants such as glyceryl ethers assist synthetic ceramide, to penetrate into the stratum corneum. However, these co-surfactants tend to disrupt the stratum corneum, so that when penetration occurs allowing the synthetic ceramide access to the lipid lamellae, there is nothing to prevent them being washed out again on contact with water. Certain phosphorylated and sulphated derivatives of ceramides have been prepared in the course of scientific investigation of natural metabolism or to make liposomes for drug delivery. Thus Karpyshev, Bushnev et al Bioorg Khim 5_(2) 238 (1979) and 5_(9) 1381 (1979) describe preparation of phosphorylated derivatives of ceramides by routes which entail the use of protective groups which are eventually removed. Japanese published application JP-A-89/299265 discloses the preparation of ceramide sulphates to be used for liposome production. SUMMARY OF THE INVENTION We have solved the problem of effective delivery of ceramides using modified naturally-occurring ceramides, that is ceramides derived from animal tissues, such as skin and brain or those derived from certain plant tissues, which have been modified by phosphorylation and/or sulphation. SUBSTITUTE SHEET Accordingly, when these modified ceramides are applied topically to the skin, together with a suitable cosmetically acceptable vehicle, they will readily penetrate the stratum corneum without permanently disrupting it, and after demodification with phosphatases or sulphatases which occur naturally in skin and which will cleave off the phosphate or sulphate groups respectively, the unmodified ceramide structures will remain locked in the desired location within the stratum corneum. Since the phosphate and/or sulphate groups, which facilitate delivery, have been removed once the ceramide is in position, it is then not possible subsequently to wash out the ceramide from the skin, so ensuring that it is available to effect repair in situ of lipid lamellae which have become damaged under dry skin conditions. o summarise: we have modified certain naturally-occurring ceramides by phosphorylation or sulphation to assist their penetration into the lipid lamellae of the stratum corneum. Once located within the lipid lamellae, naturally-occurring phosphatases and sulphatases will cleave off the phosphate or sulphate groups respectively, to leave the ceramides lodged firmly within the stratum corenum. DEFINITION OF THE INVENTION A ccordingly, one aspect of this invention provides a composition for topical application to human skin, hair or nails which comprises: i. an effective amount of at least one modified ceramide having the structure (1) below; and i. a cosmetically acceptable vehicle for the modified ceramide. SUBSTITUTE SHEET (1) 2 where A represents -CH or -CHOR or -CH=CH- or -CHOY- R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated aliphatic hydrocarbon group having from 8 to 49 carbon atoms or the group Y-0-(C a H b )- R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated, aliphatic hydrocarbon having from 8 to 28 carbon atoms; R 2 & R3 individually represent H or a phosphate residue (P.), or a sulphate residue (S0 3 θ ) , P . represents 0 θ I - p - I Λ θ R represents H, a phosphate residue (P.) , a sulphate residue (SO ) , a sugar residue or (2 ) or -0-P-OCH 2 CH 2 NH 2 (3 ) OH or -0-P-OCH 2 CH NH COOH (4 ) OH 92/06674 - 6 or o II -0-P-OCH CHOHCH OH (5) I OH or OH a is an integer of from 7 to 49 b is an integer of from 10 to 98 m is 0 or 1 Y represents H or a residue of a C 14 tθ C 22 fatty acid having the structure (7) -C-(CxHyZz)'CH_3 (7) where Z is -OH or an epoxy oxygen x is an integer of from 12 to 20 y is an integer of from 20 to 40 z is O, or an integer of from 1 to 4; 92/06674 - 7 - provided that at least one out of R , R & R is either a phosphate residue or a sulphate residue. FURTHER DISCLOSURE OF THE INVENTION The Modified Ceramide With reference to structure (1) , the group R preferably represents an aliphatic hydrocarbon group having from 12 to 30 carbon atoms, while the group R preferably represents an aliphatic hydrocarbon group having from 12 to 22 carbon atoms. Also, with reference to structure (1) , the value of "a" is preferably an integer of from 24 to 30 and the value of "b" is preferably an integer of from 44 to 60. Also, with reference to structure (1) , the group Y represents a straight chain saturated c 16 _ 18/ fatty acid residue or a straight chain all cis n-6,9 di-unsaturated c i6 - i8 fatt y acid residue. Specific examples of these modified ceramides are those having the structures (8)- (26) set out below: 0 CH 3 < C 16 H 28> C -°- C 2 H 59- C - NH ( 8 ) CH-C^OP^ ^ C, _H_. -CH=CH-CHOH 1 / 35 8 - 0 II C 23 H 47- C"NH (9) CH-CH 2 OS0 3 © C1.5..H3_1.-CH=CH-CH0H C 15 H 31- C ~ NH (10) CH-CH OP. 0 CH-CH 2 OS0 3 ° C 13 H 27 -CH=CH-CHOH 0 II C 14 H 29 "CHOH ~ C ~ NH (12) CH-CH OP. -I-" .JL 0 II C 22 H 45- CH0H - C - NH (13) C lg H 37 -CHOH-CHOH 0 II C 24 H 49 "CHOH_C - NH (14) CH-CH OP. C 18 H 37~ CHO ~ CHOH CH 3 ^ C 22 H 44 OH ) C 23 H 47- C - NH I II CH-CH 2 0-P-0CH 2 CH 2 N(CH 3 ) (15) C 23 H 47- C - NH CH-CH 2 0-P-OCH 2 CH 2 NH 2 (16) I I : 13 H 2g -CH=CH-CHOP. OH C 23 H 47- C - NH OH CH-CH 2 0-P- O CH CHNH COOH (17) c 13 H 27 -CH=CH-CHOSO Q 0 C 23 H 47 _C - NH C 13 C 23 H 47- C ~ NH C 22 H 45- CHOP i- C - NH CH-CH OP . 2 l (21) C 17 H 35 -CHOP i -CHOP. O 8 C 8 H 17 -CHOH-C-NH CH-CH 2 OP i (22) C 8 H 17 -CH=CH-CHOH O II C__H. t --CHOH-C-NH CH-CH 2 OS0 3 e (23) C_ _H . -CHOH-CHOH 23 47 C__H . -CHOSO - C-NH 22 45 3 CH-CH 2 OS0 3 e (24) C__H. -CHOSO_°-C-NH 22 45 3 CH-CH 2 OP . (25) © C. _H_ -CHOP . -CHOSO., 1/ JD 1 3 CH=CHCH 2 CH=CH(CH 2 ) 7 C-NH CH-CH 2 OP i (26) C ι 3 H 27 -CH=CH-CHOP i SUBSTITUTE SHEET 6674 χ3 SYNTHESIS OF THE MODIFIED CERAMIDES The modified ceramides according to the invention can be synthesised using a conventional method involving phosphorylation and/or sulphation. Examples of phosphorylation comprise the treatment of a naturally-occurring ceramide, or mixtures thereof, with one of the following: (i) phosphorus pentoxide (P_0 5 ) , (ii) polyphosphonic acid, ' (iii) phosphorus oxychloride, (P0C1 3 ) followed by hydrolysis, or (iv) phosphorus trichloride (PC1 3 ) followed by: (a) oxidation using, for example, chlorine, and then (b) hydrolysis. Examples of sulphation comprise the treatment of a naturally-occuring ceramide, or mixture thereof with one of the following: (i) chlorosulphonic acid, ((iiii)) tthhiioonnyyllcchhlloorriiddee,, ((SSO0CC1 2 ) , or (iii) fuming sulphuric acid. The naturally-occurring ceramide can either be synthesised or isolated from a suitable animal or plant source. Particulary preferred sources of naturally-occurring ceramides are pig skin or neutral tissue. A preferred technique for isolation of ceramides from pig skin involves the use of "pig bristle", this being the pulp or slurry obtained from the pig carcass following mechanical flailing or scrubbing of the skin to remove hair or 92/06674 - 14 - bristle prior to butchering to provide the useful parts of the animal for consumption. In accordance with this technique, the so-called pig bristle, as a pulp or slurry, is de-watered as far as it is possible, using filtration or centrifugation. The de-watered pig bristle is then preferably dried, for example with hot air, and then extracted with an organic solvent such as isopropyl alcohol and methyl alcohol, optionally together with chloroform. A mixture of ceramides can then be isolated from this solvent extract and treatment with one of the above mentioned methods, (preferably, with phosphorus pentoxide and/or chlorosulphonic acid) can then be employed in accordance with the conventional technology to achieve phosphorylation and/or sulphation, respectively, of the purified pig skin ceramides. A similar procedure involving phosphorylation and/or sulphation can be employed to modify purified naturally-occurring ceramides, to their respective phosphorylated and/or sulphated forms. The material which is subjected to sulphation or phosphorylation, whether natural or synthetic in origin, will preferably be of structure: OH in which A is -CH 2 - or -CHOH- or -CH=CH- or -CHOY- while R, R 1 and m are as defined above. Phosphorylation or, as the case may be, sulphation will preferably be carried out under conditions where any hydroxyl group present in the starting material can SUBSTITUTE SHEET 066 - 15 - react. This then leads to (at least some) formation of product compounds in which neither R 2 nor R 3 nor R 4 is H. It can also convert any other hydroxyl groups present as substituents on R or R 1 into phosphate or sulphate groups. There may be sulphation or phosphorylation of all free hydroxyl groups in the starting material. Such uncontrolled sulphation or phosphorylation is economical and is acceptable because it is intended that the sulphate or phosphate groups will be removed in vivo by naturally occurring enzymes. DEFINITION OF COMPOUNDS OF -THE INVENTION In another aspect, therefore, the invention provides modified ceramides having the structure (1) as defined above except that none of R 2 nor R 3 nor R 4 is H. FURTHER DISCLOSURE OF THE COMPOSITION The composition according to the invention comprises in its simplest form a modified ceramide of structure (1) above and a vehicle therefor to enable the modified ceramide to be dispersed onto the skin and distributed thereon. The amount of the modified ceramide, or a mixture thereof, present in the composition according to the invention is f rom 0.00001 to 50%, preferably from 0.001 to 20% and most preferably from 0.1 to 10% by weight. The Cosmetically Acceptable Vehicle The composition according to the invention also comprises a cosmetically acceptable vehicle to act as a dilutant, dispersant or carrier for the modified ceramide in the composition, so as to facilitate its distribution when the composition is applied to the skin and/or hair. Vehicles other than water can include liquid or solid emollients, solvents, humectants, thickeners and powders. 06674 - 16 - Examples of each of these types of vehicle, 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, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, tallow, lard, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, olive oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isostearic acid, pal itatic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate; Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorot ifluoroethane, propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide; Solvents, such as ethyl alcohol, methylene chloride, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, dimethyl formamide, tetrahydrofuran; TE SHEET Powders, such as chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium poJLyacrylate, 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 cosmetically acceptable vehicle will usually form from ιo to 99.9%, preferably from 50 to 99% by weight of the emulsion, and can, in the absence of other cosmetic adjuncts, form the balance of the composition. OPTIONAL SKIN BENEFIT MATERIALS AND COSMETIC ADJUNCTS A particularly convenient form of the composition according to the invention is an emulsion, in which case an oil or oily material will normally be present, together with an emulsifier to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending largely on the average hydrophilic-lyophilic balance (HLB) of the emulsifier employed. Oil or oily material The composition according to the invention can optionally comprise one or more oils or other materials having the properties of an oil. Examples of suitable oils include mineral oil and vegetable oils, and oil materials, such as those already proposed herein as emollients. Other oils or oily materials include silicone oils, both volatile and non-volatile, such as polydimethyl siloxanes. SUBSTITUTE SHEET 06 - 18 - The oil or oily material, when present for the purposes for forming an emulsion, will normally form up to 90%, preferably from 10 to 80% by volume of the composition. Emulsifier The composition according to the invention can also optionally comprise one or more emulsifiers the choice of which will normally determine whether a water-in-oil or and oil-in-water emulsion is formed. When a water-in-oil emulsion is required, the chosen emulsifier or emulsifiers should normally have an average HLB value of from 1 to 6. When an oil-in-water emulsion is required, a chosen emulsifier or emulsifiers should have an average HLB value of >6. Examples of suitable emulsifiers are set below in Table 1 in which the chemical name of the emulsifiers is given together with an example of a trade name as commercially available, and the average HLB value. 19 - Table 1 Chemical Name Trade Name HLB Value of Emulsifier Sorbitan trioleate Sorbitan tristearate Glycerol monooleate Glycerol monostearate Glycerol monolaurate Sorbitan sesquioleate Sorbitan monooleate Sorbitan monostearate Poloxyethylene (2) stearyl ether Brij 72 4.9 Poloxyethylene sorbitol beeswax derivative PEG 200 dilaurate Sorbitan monopalmitate Polyoxyethylene (3.5) nonyl phenol PEG 200 monostearate Sorbitan monolaurate PEG 400 dioleate Polyoxyethylene (5) monostearate Ethofat 60-16 9 . 0 Polyoxyethylene (4) sorbitan monostearate Polyoxyethylene (4) lauryl ether Polyoxyethylene (5) sorbitan monooleate PEG 300 monooleate - 20 - Polyoxyethylene (20) sorbitan tristearate Polyoxyethylene (20) sorbitan trioleate Polyoxyethylene (8) monostearate PEG 400 monooleate PEG 400 monostearate Polyoxyethylene 10 monooleate Ethofat 0/20 12.2 Polyoxyethylene (10) stearyl ether Brij 76 12.4 Polyoxyethylene (10) cetyl ether Brij 56 12.9 Polyoxyethylene (9-3) octyl phenol Triton X-100 13.0 Polyoxyethylene (4) sorbitan monolaurate PEG 600 monooleate PEG 1000 dilaurate Polyoxyethylene sorbitol lanolin derivative Polyoxyethylene (12) lauryl ether PEG 1500 dioleate Polyoxyethylene (14) laurate Arosurf HFL-714 14.8 Polyoxyethylene (20) sorbitan monostearate Tween 14.9 Polyoxyethylene 20 sorbitan monooleate Tween 80 15.0 Polyoxyethylene (20) stearyl ether Brij 78 15.3 SUBSTITUTE SHEET - 21 - Polyoxyethylene (20) sorbitan monopalmitate Tween 40 15.6 Polyoxyethylene (20) cetyl ether Brij 58 15.7 Polyoxyethylene (25) oxypropylene G-2162 16.0 monostearate Polyoxyethylene (20) sorbitol monolaurate Tween 20 16.7 Polyoxyethylene (23) lauryl ether Brij 35 16.9 Polyoxyeth lene (50) monostearate Myrj 53 17.9 PEG 4000 monostearate Pegosperse 4000 MS 18.7 The foregoing list of emulsifiers is not intended to be limiting and merely exemplifies selected emulsifiers which are suitable for use in accordance with the invention. It is to be understood that two or more emulsifiers can be employed if desired. The amount of emulsifier or mixtures thereof, to be incorporated in the composition of the invention, when appropriate is from 1 to 50%, preferably from 2 to 20% and most preferably from 2 to 10% by weight of the composition. Water The composition of the invention can also comprise water, usually up to 98%, preferably from 5 to 80% by volume. SUBSTΪTUTE SHEET - 22 - Silicone Surfactant The composition of the invention can also optionally comprise a high molecular weight silicone surfactant which can also act as an emulsifier, in place of or in addition to the optional emulsifier(s) already mentioned. The silicone surfactant is a high molecular weight polymer of dimethyl polysiloxane with polyoxyethylene and/or polyoxypropylene side chains having a molecular weight of from 10,000 to 50,000 and having the structure: CH, CH. CH 3 -Sl- —si- -CH_. CH. CH. where the groups R' and R" are each chosen from -H, C alkyl and - [CH 2 CH 2 0] a [CH 2 CHO] b H CH. a has a value of from 9 to 115, b has a value of from 0 to 50, x has a value of from 133 to 673, y has a value of from 25 to 0.25. Preferably, the dimethyl polysiloxane polymer is one in which: SUBSTITUTE SHEET 06674 - 23 - a has a value of from 10 to 114 b has a value of from 0 to 49 x has a value of from 388 to 402 y has a value of from 15 to 0.75 one of groups R' and R" being lauryl, and the other having a molcular weight of from 1000 to 5000. A particularly preferred dimethyl polysiloxane polymer is one in which: a has the value 14 b has the value 13 x has the value 249 y has the value 1.25 The dimethyl polysiloxane polymer is conveniently provided as a dispersion in a volatile siloxane, the dispersion comprising, for example, from 1 to 20% by volume of the polymer and from 80 to 99% by volume of the volatile siloxane. Ideally, the dispersion consists of a 10% by volume of the polymer dispersed in the volatile siloxane. Examples of the volatile siloxanes in which the polysiloxane polymer can be dispersed include polydimethyl siloxane (pentamer and/or hexamer) . A particularly preferred silicone surfactant is cyclomethicone and dimethicone copolyol, such as DC 3225C Formulation Aid available from DOW CORNING. Another is laurylmethicone copolyol, such as DC Q2-5200, also available from Dow Corning. - 24 - The amount of silicone surfactant, when present in the composition will normally be up to 25%, preferably from 0.5 to 15% by weight of the emulsion. Other Cosmetic Adjuncts Examples of conventional adjuncts which can optionally be employed include preservatives, such as para-hydroxy benzoate esters; antioxidants, such butyl hydroxy toluene; humectants, such as glycerol, sorbitol, 2-pyrrolidone-5-carboxylate, dibutylphthalate, gelatin, polyethylene, glycol, preferably PEG 200-600; buffers, such as lactic acid together with a base such as triethanolamine or sodium hydroxide; surfactants, such as glycerol ethers and other ceramides of synthetic, animal or plant origin; phospholipids; waxes, such as beeswax, ozokerite wax, paraffin wax, plant extracts, such as Aloe vera, cornflower, witch hazel, elderflower, cucumber; thickeners; activity enhancers; colourants; perfumes; and sunscreen materials such as ultrafine titanium dioxide and organic sunscreens such as p-aminobenzoic acid and esters thereof, ethylhexyl p-methoxycinnamate, 2-ethoxyethyl p-methoxycinnamate and butyl methoxydibenzoylmethane, and mixtures thereof. In a further preferred composition, the modified ceramide, or a mixture thereof t is combined with conventional ceramides, pseudoceramides, cholesterol, cholesterol fatty acids, fatty acids, triglycerides, cerebroside, phospholipid and other ingredients well known to those skilled in the art to produce a liposomal dispersion. In yet another preferred composition, the modified ceramide, or mixture thereo is dissolved in squalene or squalane, optionally together with conventional ceramides, and formulated with volatile and non-volatile silicones to produce an anhydrous or nearly anhydrous single phase system. Cosmetic adjuncts can form the balance of the composition. Use of the Composition The composition according to the invention is intended primarily as a product for topical application to human skin, especially as an agent for reducing the permeability to water of the skin, particularly when the skin is dry or damaged, in order to reduce moisture loss and generally to enhance the quality of skin. The composition can also be applied to hair and nails. The modified ceramides according to the invention have surfactant properties and can therefore also be used, in the form of a composition as herein defined, for cleansing the surface of the human body. In particular the composition can be used to cleanse the skin to remove make up or can be employed in a shampoo for cleansing the hair. In use, a small quantity of the composition, for example from 1 to 5ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the skin using the hand or fingers or a suitable device. - 26 - PRODUCT FORM AND PACKAGING The topical skin, hair or nail treatment composition of the invention can be formulated as a lotion having a viscosity of from 4,000 to 10,000 mPas, a fluid cream having a viscosity of from 10,000 to 20,000 mPas or a cream having a viscosity of from 20,000 to 100,000 mPas, or above. The composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer. For example, a lotion or fluid cream can be packaged in a bottle or a roll-ball applicator or a propelIant-driven aerosol device or a container fitted with a pump suitable for finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar. The invention accordingly also provides a closed container containing a cosmetically acceptable composition as herein defined. EXAMPLES The invention is illustrated by the following examples. SUBSTITUTE SHEET 06674 - 27 - Example 1 This example illustrates a high internal phase water-in-oil emulsion in accordance with the invention. A high internal phase water-in-oil emulsion having the following formulation was prepared: % w/w Fully hydrogenated coconut oil 3.9 Phosphorylated ceramide having the structure (8) 0.1 Brij 92* 5 Bentone 38 0.5 Preservative 0.3 MgS0 4 7H 2 0 0.3 Butylated hydroxy toluene 0.01 Perfume qs Water to 100 *Brij 92 is polyoxyethylene (2) oleyl ether Example 2 This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: i. liquid paraffin replaced the fully hydrogenated coconut oil, and ii. the modified ceramide was sulphated and had the structure (9) . - 28 - Example 3 This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: The phosphorylated ceramide had the structure (10) . Example 4 This example illustrates an oil-in-water cream containing an ester of the invention. An oil-in-water cream emulsion having the following formulation was prepared: % w/w Mineral oil 4 Sulphated ceramide having the structure (11) 0.1 Brij 56* 4 Alfol 16RD* 4 Triethanola ine 0.75 Butane-l,3-diol 3 Xanthan gum 0.3 Preservative 0.4 Perfume qs Butylated hydroxy toluene 0.01 Water to 100 *Brij 56 is cetyl alcohol POE (10) Alfol 16RD is cetyl alcohol - 29 - Example 5 This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following change: the modified ceramide was phosphorylated and had the structure (12) , as herein defined. Example 6 This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following changes: sulphated ceramide was that having the structure (13) as herein defined. Example 7 This example illustrates an alcoholic lotion containing an amide of the invention. The lotion had the following formulation: w/w Phosphorylated ceramide having the structure (14) 0.2 Ethanol 40 Perfume qs Butylated hydroxy toluene 0.01 Water to 100 - 30 - Example 8 This example illustrates an alcoholic lotion containing an amide of the invention. The lotion had the following formulations: % w/w Sulphated ceramide having the structure (15) 0.2 Dimethylsulphoxide 10 Ethanol 40 Antioxidant 0.1 Perfume qs Water to 100 Examples 9 and 10 The following compositions according to the invention represent lotions which can be used in the treatment of dry skin: % w/w 9 10 Phosphorylated ceramide having the structure (16) 1.5 Sulphated ceramide having the structure (17) - 0.5 Perfume 0.1 0.1 Hydroxyethyl cellulose 0.4 0.4 Absolute ethanol 25 25 p-methyl benzoate 0.2 0.2 Sterilised demineralised water to 100 to 100 - 31 - Examples 11 and 12 The following compositions according to the invention represent lotions which can be used in the treatment of dry skin: % w/w 11 JL2 The phosphorylated ceramide having the structure (18) 0.08 - The sulphated ceramide having the structure (19) - 0.15 Ethanol 10 10 Perfume 0.5 0.5 Distilled water to 100 to 100 Example 13 This example illustrates a high internal phase water-in-oil emulsion in accordance with the invention. A high internal phase water-in-oil emulsion having the following formulation was prepared: SUBSTITUTE SHEET - 32 - w/w Fully hydrogenated coconut oil 3.9 Phosphorylated ceramide having the structure (20) 0.1 Brij 92* 5 Bentone 38 0.5 Preservative 0.3 gS0 4 7H 2 0 0.3 Butylated hydroxy toluene 0.01 Perfume qs Water to 100 *Brij 92 is polyoxyethylene (2) oleyl ether Example 14 This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: i. liquid paraffin replaced the fully hydrogenated coconut oil, and ii. the phosphorylated ceramide had the structure (21) . SUBSTITUTE SHEET - 33 - Example 15 This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: The phosphorylated ceramide had the structure (22) . Example 16 This example illustrates an oil-in-water cream containing an ester of the invention. An oil-in-water cream emulsion having the following formulation was prepared: w/w Mineral oil 4 Sulphated ceramide having the structure (23) 0-1 Brij 56* 4 Alfol 16RD* 4 Triethanolamine 0.75 Butane-l,3-diol 3 Xanthan gum 0.3 Preservative 0.4 Perfume qs Butylated hydroxy toluene 0.01 Water to 100 *Brij 56 is cetyl alcohol POE (10) Alfol 16RD is cetyl alcohol Example 17 This example also illustrates an oil-in-water emulsion containing an ester of the invention, in which the formulation of example 4 was prepared but with the following change: the sulphated ceramide was that having structure (24) , as herein defined. Example 18 This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following changes: the modified ceramide was both sulphated and phosphorylated and had the structure (25) as herein defined. Example 19 This example illustrates an alcoholic lotion containing an amide of the invention. The lotion had the following formulation: w/w Phosphorylated ceramide having the structure (8) 0.2 Ethanol 40 Perfume qs Butylated hydroxy toluene 0.01 Water to 100 35 Example 20 This example illustrates an alcoholic lotion containing an amide of the invention which is suitable for application to nails. The lotion had the following formulations: w/w Sulphated ceramide having the structure (9) 0.2 Dimethylsulphoxide 10 Ethanol 40 Antioxidant 0.1 Perfume Water to 100 - 36 - Examples 21 and 22 The following compositions according to the invention represent lotions which can be used in the treatment of dry, unmanageable hair. % w/w 21 22 Phosphorylated ceramide having the structure (10) 1.5 - Sulphated ceramide having the structure (11) - 0.5 Perfume 0.1 0.1 Hydroxyethyl cellulose 0.4 0.4 Absolute ethanol 25 25 p-meth l benzoate 0.2 0.2 Sterilised demineralised water to 100 to 100 Examples 23 and 24 The following compositions according to the invention represent lotions which can be used in the treatment of dry skin, hair or nails: w/w 23 24 The phosphorylated ceramide having the structure (12) 0.08 The sulphated ceramide having the structure (13) Ethanol Perfume Distilled water Example 25 This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following change: the modified ceramide was phosphorylated and had the structure (12), as herein defined.

Claims: - 38 - CLAIMS 1. A composition suitable for topical application to skin, hair or nails, which comprises an amount of from 0.00001 to 20% by weight of a modified ceramide, together with a cosmetically acceptable vehicle for the modified ceramide, the modified ceramide having the structure (1) : 0 II R-(CHOR 2 ) " HI-C-NH I CH-CH 2 0R 4 (1) I R X -A-CHOR 3 2 where A represents -CH_ or -CHOR or -CH=CH- or -CHOY. . - R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated, aliphatic hydrocarbon group having from 8 to 49 carbon atoms or the group Y-0-(C a H b )- i R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated, aliphatic hydrocarbon having from 8 to 28 carbon atoms; 2 3 . R & R individually represent H, a phosphate residue (P.), or a sulphate residue (so 3 ^) , P . represents 0 β P = 0 0 θ 4 R represents H, a phosphate residue (P.), a sulphate residue SO_ , a sugar residue or the groups 0 II & ■ 0-P-OCH 2 CH 2 N(CH 3 ) 2 (2) I or • 0-P-OCH 2 CH 2 NH 2 ( 3 ) OH or -0-P-OCH 2 CH 2 NH 2 COOH (4 ) OH or 0 II -0-P-OCH 2 CHOHCH OH (5) OH or a is an integer of from 7 to 49 b is an integer of from 10 to 98 m is 0 or 1 Y represents H or a residue of a C 14 tθ C 22 fatt ^ acid having the structure (7) 0 -C-( v CxHyZz)'CH,3 (7) where Z is -OH or an epoxy oxygen x is an integer of from 12 to 20 y is an integer of from 20 to 40 z is O, or an integer of from 1 to 4; 4 - 41 - provided that at least one out of R 2 , R 3 and R 4 is either a phosphate residue or a sulphate residue. 2. A composition according to claim 1 wherein neither R 2 nor R 3 nor R 4 represents H. 3. A method for the treatment of skin, hair or nails which comprises topical application thereto of a composition according to cliam 1 or claim 2. 4. The use of at least 0.00001% by weight of a modified ceramide as defined in claim 1 or claim 2 as an agent for skin water barrier repair, in a topical composition comprising a major proportion of a cosmetically acceptable vehicle for the ceramide. 5. The use of at least 0.00001% by weight of a modified ceramide as defined in claim 1 or claim 2 as an agent for improving nails. 6. The use of at least 0.00001% by weight of a modified ceramide as defined in claim 1 or cliam 2 as an agent for improving hair. 7. A process for synthesising the modified ceramide as defined in claim 1 or cliam 2 which comprises the step of phosphorylation and/or sulphation of naturally- occurring cermaide, or a mixture of naturally-occurring ceramides. 8. A process according to claim 7 wherein the naturally-occurring ceramide(s) are of structure: 2 CH 2 OH R 1 -A-CH0H - 42 - wherein A is -CH 2 - or - CHOH- or -CH=CH- or -CHOY- and R, R 1 and m are as defined in claim 1. 9. Modified ceramides having the structure: 0 II CH-CH OR (1) R 1 -A-CHOR 3 2 where A represents -CH or -CHOR or -CH=CH- or -CHOY- R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated aliphatic hydrocarbon group having from 8 to 49 carbon atoms or the group Y-0-(C a H b )- R represents a linear or branched, saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated, aliphatic hydrocarbon having from 8 to 28 carbon atoms; 2 3 . . . R & R individually represent a phosphate residue (P.), or a sulphate residue S0 3 θ >' P. represents 0 θ P = 0 „, θ 4 R represents a phosphate residue (P . ) , a Q ••*- sulphate residue (SO )., a sugar residue or the groups © -0-P-OCH 2 CH 2 N(CH 3 ) 2 (2) or 0 II -0-P-OCH 2 CH 2 NH 2 (3) OH or 0-P-OCH 2 CH 2 NH 2 COOH (4) I OH SUBSTITUTE SHEET - 44 or 0 II -0-P-OCH 2 CH0HCH 2 OH (5) OH or OH a is an integer of from 7 to 49 b is an integer of from 10 to 98 m is 0 or 1 Y represents H or a residue of a C 14 tθ C 22 fatt y acid having the structure (7) -C-(CxHyZz)'CH_3 (7) where Z is -OH or an epoxy oxygen x is an integer of from 12 to 20 y is an integer of from 20 to 40 z is 0, or an integer of from 1 to 4.

Inventors: CRITCHLEY PETER, KIRSCH SUSAN, RAWLINGS ANTHONY VINCENT, SCOTT IAN RICHARD, CRITCHLEY, PETER, KIRSCH, SUSAN, RAWLINGS, ANTHONY, VINCENT, SCOTT, IAN, RICHARD
Applicants: UNILEVER NV, UNILEVER PLC
Application year: 1991
Main classification: A61K7
IPC codes: A61K8, A61Q3, A61Q5, A61Q17, A61Q19, C07C305, C07F9