DISACCHARIDES

Abstract: A composition suitable for topical application to mammalian skin, for promoting or enhancing the growth of hair, comprises a disaccharide including a uronic acid residue and a hexosamine residue.

Description: Field of invention The invention relates to novel oligosaccharides, particularly to esterified disaccharides containing a uronic acid residue and a hexosamine residue joined through a glycosidic linkage. The invention also relates to the use of these esterified disaccharides, particularly in cosmetic and pharmaceutical compositions. Prior Art Certain α-1,4 esterified disaccharides, together with their synthesis and use in controlling the coagulation of blood, are described by Choay S.A. in EP-A-0 064 012. These α-1,4 disaccharides are said to have the structure: where Z represents a functional nitrogen group, such as an azide or a group having the structure -NHB, in which B represents -H or a functional group such as acetyl or sulphate as a salt with an organic or mineral cation; M represents -H or -SO₃M₁, where M₁ is an organic or metallic cation, particularly an alkali metal; or an acetyl group; R represents a C₁ to C₄ alkyl radical, especially methyl; or an aryl radical; A represents a functional group such as an acid or -COOR₁, where R₁ represents -H or a C₁ to C₄ alkyl radical, especially methyl; or a metal, especially an alkali metal. The Hair Growth Cycle It should be explained that in most mammals, hair does not grow continuously, but undergoes a cycle of activity involving alternate periods of growth and rest. The hair growth cycle can be divided into three main stages, namely: i) the growth phase known as anagen, during which the hair follicle penetrates deep into the dermis with the cells of the bulb dividing rapidly and differentiating to form the hair, ii) the transitional stage known as catagen which is heralded by the cessation of mitosis, and during which the follicle regresses upwards through the dermis and hair growth ceases, iii) the resting stage known as telogen in which the regressed follicle contains a small secondary germ with an underlying ball of tightly packed dermal papilla cells. The initiation of a new anagen phase is revealed by rapid cell proliferation in the germ, expansion of the dermal papilla and elaboration of basement membrane components. The hair cycle is then repeated many times until, most of the hair follicles spend an increasing proportion of their time in the telogen stage, and the hairs produced become finer, shorter and less visible; this is known as terminal to vellus transformation. In the human male subject this consequence is seen as the onset of male pattern baldness. Alleged Baldness Cures Although there have been many claims in the scientific literature to the promotion or maintenance of hair growth or regrowth, by the topical application of hair tonics and the like, particularly in the human male subject, none has yet been widely accepted by the consumer as being both safe and effective. Perhaps the only means which has met with partial success for growing hair on the bald or balding human head is by transplantation of hair to the bald areas. This is however an extremely painful operation and is not always successful. Furthermore, it is immediately apparent to the casual observer that the subject has received a hair transplant, and it may take many months or even years before hair regrowth, following this operation, assumes an appearance which resembles that of the original naturally growing hair. Among the many hair regrowth studies that have been reported in the literature, the work of Meyer et al (1961) in the Proceedings of the Society of Experimental and Biological Medicine, 108 , 59-63, is worthy of mention. Meyer and his co-workers repeatedly injected acid mucopolysaccharides intracutaneously into the skin of shaved rabbits and reportedly observed initiation of the hair growth cycle with stimulation of hair growth which in some instances appeared to be thicker than usual. They found that heparitin (also known as heparan) sulphate was particularly active, while dermatan sulphate and chondroitin-6-sulphate were also active in this respect, but to a lesser extent. It has also been reported by Frajdenrajch in EP-A-0 035 919 to include chondroitin sulphate in a hair composition in order to prevent loss and encourage growth of the hair. Also, Shansho Seijaku in JA-59/186911 describe a shampoo containing a mucopolysaccharide such as chondroitin sulphate. There are other references, mainly of Japanese origin, which claim the use of chondroitin sulphate in preparations for topical application to human skin, particularly as hair tonics. It is believed that molecules having a molecular weight of greater than about 1500 are unlikely to penetrate skin to any significant extent when applied topically, and accordingly, it is unlikely that polysaccharides such as chondroitin sulphate having a molecular weight of many thousands could penetrate the skin of the scalp, following topical application, and diffuse into the immediate environment of the hair follicle in order to initiate or enhance hair growth. It has however now been discovered that oligosaccharides of smaller molecular weight, including certain disaccharides which are known for use in compositions other than for the treatment of baldness, can diffuse through the outer layers of the skin to the immediate environment of the hair follicle, where they can positively increase hair growth. It has accordingly been shown that application of these materials to mammalian skin in the region of vellus hair can convert vellus hair to growth as terminal hair. It has also been shown that the rate of terminal hair growth in mammalian skin can be increased by applying these materials to mammalian skin in the region of terminal hair. According to a first aspect of this invention there is provided a method for increasing the rate of terminal hair growth in mammalian species, which comprises applying to mammalian skin in the region of terminal hair, an effective amount of a composition comprising a disaccharide including a uronic acid residue having the structure: and a hexosamine residue having the structure: where X is - H, C₁ to C₄ alkyl, -CO(CH₂) m CH₃, -SO₃M, or an aryl radical, X' is - H, -CO(CH₂) m CH₃, or - SO₃M, Y is - H, C₁ to C₄ alkyl or M, and M is - H or a metallic or organic cation, and m is O or the integer 1 or 2; the groups designated X being the same or different, one -OH group from each pyranose ring structure being linked by a glycosidic linkage having the configuration α-1,3, β-1,3, α-1,4 or β-1,4; and the -COOY, -CH₂OX and -OX groups being of either configuration with respect to the pyranose ring. The invention also extends to the use of a disaccharide as defined above in the preparation of a composition for the treatment of baldness. In a second aspect this invention provides a composition suitable for topical application to mammalian skin for promoting or enhacing the growth of hair, said composition comprising an effective amount of a disaccharide including a uronic acid residue and a hexosamine residue having the structures (50) and (51) defined above, but excluding disaccharides of the structure: We have found that the molecular charge and polarity of an oligosaccharide will influence its skin penetration. The more polar or highly charged the oligosaccharide, the less likely it is to penetrate the skin, and for this reason it is advantageous to employ oligosaccharides which are esterified to an extent that will reduce their molecular charge. The preferred disaccharides that are selected for optimum penetration of the skin of the scalp are those which have at least 2, most preferably at least 6 ester groups per molecule. The topical composition The composition is preferably one comprising a solid, semi-solid or liquid physiologically acceptable vehicle. The nature of the vehicle employed in the preparation of any particular composition will depend on the method intended for administration of that composition. The vehicle can be inert or can possess physiological or pharmaceutical benefits of its own. The relative amounts of the disaccharide, and the vehicle is unimportant, as all that is necessary is the supply of an effective amount of the disaccharide for the purpose for which it is administered, the vehicle merely acting as a carrier or diluent of these materials. The disaccharide The disaccharides include those disclosed in EP-A-0 064 012 to Choay S.A., but with a disclosed utility other than for the promotion of hair growth or regrowth. Particularly preferred examples of known disaccharides which can be used in the method of the invention have the following structures where the designation of X, X', Y and M are as hereinbefore defined. A generic structure of a known disaccharide based on those disclosed in EP-A-0 064 012 to Choay S.A. is: Specific examples of the esterified disaccharide (52) have the structures shown as (53) to (59). Specific examples of further esterified disaccharides similar to but not included in the disclosure of EP-A-0 064 012 to Choay S.A., have the structures shown on (60) to (63): Also suitable for use in methods according to the invention are oligosaccharides produced by chemical cleavage of glycosaminoglycans especially chondrosine, having the structure (30) which can be obtained by acid hydrolysis of chondroitin sulphate, and its N-acetyl, and its N-acetyl, O-sulpho derivatives, having the structures (31) and (32) respectively. The derivation of these compounds will now be described by way of illustration. The disaccharide chondrosine (30) was obtained from chondroitin sulphate by acid hydrolysis. 10g of chondroitin sulphate was hydrolysed with 200ml of 2N sulphuric acid by refluxing at 100°C for 4 hours. The resulting hydrolysate was chromatographed on Dowex 50W-X8 (200-400 mesh) resin in the hydrogen form. The column was eluted with 0.2N sulphuric acid and all fractions were tested with ninhydrin/ferric chloride reagent. The first large, broad peak gave a yield of chondrosine after neutralisation with saturated barium hydroxide and lyophilisation to a dry powder. The method employed was that described by Olavesen & Davidson, J.Biol.Chem. 240(3), 992-996 (1965). N-acetylchondrosine (31) was prepared by selective N-acetylation of chondrosine using acetic anhydride. 500mg chondrosine was dissolved in 500 ml of bicarbonate buffer and cooled to 0-5°C. (Bicarbonate buffer was prepared by mixing 10ml 0.1M Na₂CO₃ and 90ml 0.1M NaHCO₃ having a pH value of 9. To this was added 0.22ml of acetic anhydride with stirring. The mixture was then left standing at 0°C overnight. It was then added to a Dowex (Registered Trade Mark) 50W-X8 (200-400) column in the acid form. Elution with three bed volumes of distilled water and lyophilisation of the aqueous eluate produced a white fluffy solid which was characterised as N-acetylchondrosine by I.R. and N.M.R. spectroscopy. The method employed was that described by Olavesen & Davidson, Ibid. Sulphation of the product in the C-6 position of the hexosamine moiety was achieved by using triethylamine-N-sulphonic acid. To a mixture of 5ml dimethylformamide, 7.5ml benzene and 0.5ml pyridine was added 500mg of N-acetylchondrosine after it had been evaporated several times from dry benzene. 9.12mg of triethylamine-N-sulphonic acid was added and the reaction vessel shaken for 26 hours at room temperature. The resulting solution was evaporated at reduced pressure to a yellow syrup (bath temp. <50°C) which was extracted with 2 x 5ml ether. The resulting oil was extracted with 10ml chloroform to remove any residual sulphonic acid. Chloroform washings and insoluble solids were washed in situ with 4 x 5ml water. The water fractions were combined and lyophilised to give N-acetyl chondrosine-6-O-sulphate (32), as a white fluffy solid which was characterised by I.R. and N.M.R. and by T.L.C. The method employed was that described by Olavesen & Davidson, Biochim. Biophys. Acta., 101, 245-251 (1965). Also suitable for use in compositions according to the invention are low molecular weight limit digests of heparan sulphate, hyaluronic acid and chondroitin sulphate produced by the relevant enzyme, namely heparitinase, hyaluronidase and chondroitinase. Also suitable for use in methods according to the invention is hyalobiouronic acid having the structure: The amount of the disaccharide to be incorporated with a suitable vehicle into compositions for topical use can vary widely, but in general, an amount of from 0.01 to 10%, preferably from 0.1 to 5% by weight of the composition will provide an adequate dose to the skin after topical application. Synthesis of Disaccharides As already indicated, one possible route for synthesising disaccharides is by subjecting intact glycosaminoglycan chains to partial hydrolysis to yield oligosaccharides comprising at least one disaccharide having a uronic acid residue linked to a hexosamine residue. Such disaccharides can then be modified. Disaccharides having at least one uronic acid residue linked in the β configuration through the C-1 position to a hexosamine residue, or certain olisaccharides having at least one hexosamine residue linked in the α or β configuration through the C-1 position to a uronic acid residue, can be prepared by condensation of relevant uronic acid and hexosamine residues. A relevant condensation reaction carried out in the presence of nitromethane and p-toluenesulphonic acid is desribed by David & Veyrieres in Carbohydrate Research 40 , 23 (1975). The Vehicle The composition should also comprise a cosmetically or physiologically acceptable vehicle to enable the disaccharide to be conveyed to the skin in an appropriate dilution. 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 disaccharide and which therefore ensure that it can be applied to and distributed evenly over the hair and/or scalp at an appropriate concentration. The vehicle is preferably one which can aid penetration of the disaccharide into the skin to reach the immediate environment of the hair follicle. Compositions according to this invention can include water as a vehicle, and/or at least one cosmetically acceptable vehicle other than water. Vehicles other than water that can be used in compositions according to the invention can 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, isopropyl 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, polyethylene glycol, triethylene glycol, lanolin, castor oil, acetylated lanolin alcohols, petroleum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristylmyristate; Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluorethane, monochlorodifluoromethane, trichlorotrifluorethane, 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, tetrahydrofuran; Humectants, such as glycerin, sorbitol, sodium 2-pyrrolidone-5-carboxylate, soluble collagen, dibutyl phthalate, gelatin; 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 vehicle in the composition, including water if present, should preferably be sufficient to carry at east a portion of the disaccharide to the skin in an amount which is sufficient effectively to enhance hair growth. The amount of the vehicle can comprise the balance of the composition, particularly where little or no other ingredients are present in the composition can accordingly comprise from 10 to 99.99%, preferably from 50 to 99.5% and ideally from 90 to 99% by weight of the vehicle or vehicles. Perfume The composition according to the invention 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 will form from 0.01 to 10% by weight of the composition. Activity Enhancer The composition according to the invention can also optionally comprise an activity enhancer whose presence further improves the delivery to the skin of the disaccharide. The activity enhancer accordingly effectively increases the partition of the esterified oligosaccharide into the skin from the composition when applied topically. While screening a series of non-electrolytes for their ability to function as activity enhancers, it was observed that they were all compounds which were capable of substantially increasing the cloud point temperature of nonionic surfactants. Such compounds included short chain alkanols, diols and short chain fatty acids. By contrast, other non-electrolytes which reduce the cloud point temperature of nonionic surfactants, such as long chain alcohols, for example, butan-1-ol and cyclohexanol; polyols, for example sorbitol and propan-1,2,3-triol, do not function as activity enhancers. An activity enhancer is accordingly defined as a non-electrolyte which is capable, at a concentration of 5% by weight of increasing the cloud point temperature of a 0.025M aqueous solution of polyoxyethylene(8)nonylphenyl ether by at least 10°C. Preferably the activity enhancer is one which is capable of increasing the cloud point temperature by at least 15°C, most preferably by at least 20°C. It should be explained that the "cloud point" is a measure of the inverse solubility of a nonionic surfactant with temperature and can be determined by heating a standard clear aqueous solution of the nonionic surfactant until the solution becomes visibly cloudy and then measuring the temperature. The cloud point temperature can conveniently be determined automatically using the equipment and method described by Baum et al in Mat. Res. Std. 4 26 (1964). Examples of suitable compounds functioning as activity enhancers, together with the respective elevated cloud point temperature obtained in each case when using the standard test defined hereinbefore are listed below in Table 1. "Synperonic" mentioned there is a Registered Trade Mark. Elevation of the cloud point temperature of a 0.025M aqueous solution of polyoxyethylene(8)nonylphenyl ether in the presence of activity enhancers Activity Enhancer (5% by weight) 0.025M aqueous solution of polyoxyethylene (8) nonyl phenyl ether (SYNPERONIC NP8 ex ICI) Cloud point temperature (°C) Elevation of cloud point temperature None (control) 33.5 0 2-methyl propan-2-ol 55.0 21.5 Propan-2-ol 56.0 22.5 Ethyl-hydroxypropanoate 52.1 18.6 Hexan-2,5-diol 52.0 18.5 POE(2) ethyl ether 46.0 12.5 Di(2-hydroxypropyl) ether 44.8 11.3 Pentan-2,4-diol 48.0 14.5 Acetone 46.3 12.8 POE(2) methyl ether 43.5 10.0 2-hydroxypropionic acid 45.0 11.5 Propan-1-ol 53.0 19.5 1,4 Dioxane 44.0 10.5 Tetrahydrofuran 45.0 11.5 Butan-1,4-diol 45.0 11.5 Other ingredients The composition optionally can contain ingredients other than those already mentioned depending on the form of the intended product. It is, for example, possible to include antiseptics, preservatives, antioxidants, emulsifiers, colouring agents and detergents. It is also possible to include other materials which inluence hair regrowth such as minoxidil and derivatives thereof. The composition can also be employed as a vehicle for a wide variety of cosmetically or pharmaceutically active ingredients, particularly ingredients which have some beneficial effect when applied to the skin other than the promotion of hair growth. The total amount of optional ingredients can form the balance of up to 84.99% by weight of the composition. Process for preparation of composition The invention also provides a process for the preparation of a composition suitable for topical application to mammalian skin, particularly to the hair and/or scalp of the human subject which comprises mixing a disaccharide as specified above with a suitable cosmetically or physiologically acceptable vehicle, to provide a composition containing the oligosacchharide at a concentration of from 0.01 to 10% by weight. Form of composition The composition can be formulated as liquids, for example as a lotion, shampoo, milk or cream for use in conjunction with an applicator such as a roll-ball applicator, or a spray device such as an aerosol can containing propellant, or a container fitted with a pump to dispense the liquid product. Alternatively, the composition of the invention can be solid or semi-solid, for example sticks, creams or gels, for use in conjunction with a suitable applicator or simply a tube, bottle or lidded jar, or as a liquid-impregnated fabric, such as a tissue wipe. The invention accordingly also provides a closed container containing a composition as herein defined. Use of compositions As mentioned, the invention also provides for the use of a disaccharide in the topical treatment of baldness. The compositions according to the invention are primarily intended for topical application to mammalian skin, particularly to the scalp of the human subject, especially where the head is already bald or balding. The compositions can also be applied prophilactically to the hair and hence the scalp to reduce or prevent the onset of baldness. The amount of the composition and the frequency of application to the hair and/or scalp can vary widely, depending on personal needs, but it is suggested as an example that topical application of from 1 to 5g daily containing from 0.001 to 1g of a selected esterified oligosaccharide over the period of at least six months will in most cases result in an improvement in hair growth. Efficacy testing The efficacy of the compositions according to the invention was examined using the rat as an animal model, in order to assess both the duration and amount of hair growth, following daily administration of such compositions. For this purpose, hair was clipped from the treatment area at regular intervals and weighed as an index of hair production. The increased duration of anagen phase was apparent from growth curves obtained by plotting weight of hair recovered from clippings against duration of the experiment. This model was validated using minoxidil, a compound known to stimulate hair growth, as a positive control. Ability to increase hair production and ability to increase the duration of anagen phase, are both required attributes of any product for reversing baldness. EXAMPLES The invention is illustrated by the following examples: Example 1 This Example illustrates a lotion according to the invention which is suitable for topical application to the scalp in order to promote hair growth. The lotion has the following formulation: % w/w disaccharide structure (53) 0.1 ethanol 99.995 perfume q.s. Example 2 This Example illustrates a hair tonic which is suitable for application to hair or scalp. The hair tonic has the following formulation: % w/w disaccharide : structure (54) 0.8 ethanol 50 water 49 perfume q.s. Example 3 This Example also illustrates a lotion which is suitable for topical application to the scalp. The lotion has the following formulation: % w/w disaccharide : structure (55) 1.5 propan-2-ol 10 ethanol 88.5 perfume q.s. Example 4 This Example also illustrates a hair tonic which is suitable for application to hair or scalp. The hair tonic has the following formulation: % w/w disaccharide : structure (56) 0.2 ethanol 40 water 59.80 perfume q.s. Examples 5 to 8 The following formulations represent lotions which can be used topically in the treatment of bald or balding male or female heads. % w/w 5 6 7 8 Hydroxyethyl cellulose 0.4 - 0.4 - Absolute ethanol 25 25 25 25 Propane-1,2-diol - - 38.4 38.4 Butane-1,3-diol 38.4 38.8 - - Paramethyl benzoate 0.2 0.2 0.2 0.2 Disaccharide structure (57) 5 - - - Disaccharide structure (58) - 1 - - Disaccharide structure (59) - - 0.8 - Disaccharide structure (60) - - - 0.6 Perfume 1 1 1 1 Water to 100 100 100 100 Examples 9 to 12 The following formulations represent creams which can be used in the treatment of baldness. % w/w 9 10 11 12 Cetyl alcohol polyoxyethylene (10) 4 4 4 4 Cetyl alcohol 4 4 4 4 Mineral oil 4 2 - - Paraffin wax - 2 4 - Partial glyceride of palmitic and stearic acids - - - 4 Disaccharide : structure (30) 2 - - - Disaccharide : structure (61) - - - 1 Disaccharide : structure (62) - 1.5 - - Disaccharide : structure (63) - - 2 - Triethanolamine 0.75 0.75 0.75 0.75 Butane-1,3-diol 3 3 3 3 Xanthan gum 0.3 0.3 0.3 0.3 Preservative 0.4 0.4 0.4 0.4 Perfume q.s. q.s. q.s. q.s. Water to 100 100 100 100 Example 13 This Example illustrates a water-in-oil high internal phase emulsion containing a disaccharide. The emulsion consisted of 10% by volume oily phase and 90% by weight aqueous phase. The oily phase and the aqueous phase had the following consitution: % w/w Oily phase Sorbitan monooleate 20 Quartenium-18 hectorite 5 Liquid paraffin 75 Aqueous phase Disaccharide : 0.5 Xanthan gum 1 Preservative 0.3 Perfume q.s. Sodium chloride (1% w/w solution) to 100 The emulsion was prepared by taking 10 parts by volume of the oily phase and to it adding slowly with stirring 90 parts by volume of the aqueous phase. The high internal phase water-in-oil emulsion so formed can be applied topically to the scalp, to improve hair growth and regrowth. Examples 14 to 17 The following formulations represent lotions which can be used topically in the treatment of bald or balding male or female heads. % w/w 14 15 16 17 Hydroxyethyl cellulose 0.4 - 0.4 - Absolute ethanol 25 25 25 25 Propane-1,2-diol - - 38.4 38.4 Butane-1,3-diol 38.4 38.8 - - Paramethyl benzoate 0.2 0.2 0.2 0.2 Disaccharide structure (30) 5 1 - - Disaccharide structure (31) - 1 4 - Disaccharide structure (32) - - 1 3 Disaccharide structure (33) 2 - - 3 Perfume 1 1 1 1 Water to 100 100 100 100 Examples 18 to 21 The following formulations represent creams which can be used in the treatment of baldness. % w/w 18 19 20 21 Cetyl alcohol polyoxyethylene (10) 4 4 4 4 Cetyl alcohol 4 4 4 4 Mineral oil 4 2 - - Paraffin wax - 2 4 - Partial glyceride of palmitic and stearic acids - - - 4 Disaccharide 6 6.5 4 4.5 Triethanolamine 0.75 0.75 0.75 0.75 Butane-1,3-diol 3 3 3 3 Xanthan gum 0.3 0.3 0.3 0.3 Preservative 0.4 0.4 0.4 0.4 Perfume q.s. q.s. q.s. q.s. Water to 100 100 100 100 The following examples 22 to 29 illustrate shampoos for use in washing the hair and scalp, and for promoting hair growth on the scalp. In these examples "Briphos" and "Polyquart" are Registered Trade Marks. Example 22 % w/w Monoethanolamine lauryl sulphate : 100% AD 20 POLYQUART H : 50% active 3 BRIPHOS 03D 1.7 Coconut diethanolamide 5 Disaccharide : structure (56) 1 Perfume q.s. Water to 100 pH adjusted to 6.5 Example 23 % w/w Sodium lauryl ether sulphate (3 EO) : 100% AD 12 POLYQUART H : 50% active 0.3 BRIPHOS 03D 1 Disaccharide : structure (57) 2 Perfume q.s. Water to 100 pH adjusted to 6.5 Example 24 % w/w Sodium lauryl ether sulphate ( 2 EO) : 100% AD 12 POLYQUART H : 50% active 3 BRIPHOS 03D 1 Opacifier 9 Disaccharide : structure (58) 5 Perfume q.s. Water to 100 pH adjusted to 6.5 Examples 25 to 29 The following Examples 43 to 47 illustrate powder compositions according to the invention which can be applied topically to the scalp. % w/w 25 26 27 28 29 Chemically modified starch 5 - 5 - 5 Chemically modified cellulose - 5 - 5 - Boric acid 10 10 10 10 10 Zinc oxide 5 5 5 5 5 Disaccharide : structure (59) 5 - - - - Disaccharide : structure (60) - 10 - - - Disaccharide : structure (61) - - 2 - - Disaccharide : structure (62) - - - 4 - Disaccharide : structure (63) - - - - 1 Perfume q.s. q.s. q.s. q.s. q.s. Chalk 10 10 10 10 10 Talc to 100 100 100 100 100

Claims: A method for increasing the rate of terminal hair growth in mammalian species, which comprises applying to mammalian skin in the region of terminal hair, an effective amount of a composition comprising and a hexosamine residue having the structure: where X is - H, C₁ to C₄ alkyl, -CO(CH₂) m CH₃, -SO₃M, or an aryl radical, X' is - H, -CO(CH₂) m CH₃, or - SO₃M, Y is - H, C₁ to C₄ alkyl or M, and M is - H or a metallic or organic cation, and m is 0 or the integer 1 or 2; the groups designated X being the same or different, one -OH group from each pyranose ring structure being linked by a glycosidic linkage having the configuration α -1,3, β -1,3, α -1,4 or β -1,4; and the -COOY, -CH₂OX and -OX groups being of either configuration with respect to the pyranose ring. A method according to claim 1 in which the disaccharide has the structure: A method according to claim 2, in which the disaccharide in chosen from those having the following structures: A composition suitable for topical application to mammalian skin for promoting or enhancing the growth of hair, said composition comprising an effective amount of a disaccharide including a uronic acid residue having the structure: and a hexosamine residue having the structure: where X is - H, C₁ to C₄ alkyl, -CO(CH₂) m CH₃, -SO₃M, or an aryl radical, X' is - H, -CO(CH₂) m CH₃, or - SO₃M, Y is - H, C₁ to C₄ alkyl or M, and M is - H or a metallic or organic cation, and m is O or the integer 1 or 2; the groups designated X being the same or different, one -OH group from each pyranose ring structure being linked by a glycosidic linkage having the configuration α -1,3, β -1,3, α -1,4 or β -1,4; and the -COOY, -CH₂OX and -OX groups being of either configuration with respect to the pyranose ring, but excluding disaccharides of the structure: A composition according to claim 3 or 4, in which the disaccharide is chosen from those having the following structures: A composition according to any of claims 4 to 5, in which the effective amount of the disaccharide present in the composition is from 0.01 to 10% by weight. A composition according to any of claims 4 to 6, in which the effective amount of the disaccharide present in the composition is from 0.01 to 5% by weight. A composition according to any of claims 4 to 7, in which the carrier forms from 10 to 99.99% by weight. A composition according to any of claims 4 to 8, in which the carrier forms from 50 to 99.5% by weight. A composition according to any of claims 4 to 9, which additionally comprises a perfume. A composition according to any of claims 4 to 10, which additionally comprises an activity enhancer. A composition according to any of claims 4 to 11, which is in the form of a cream, a gel, a lotion or a stick. A method for the conversion of vellus hair to growth as terminal hair, which comprises applying to mammalian skin in the region of vellus hair, an effective amount of a composition according to any of claims 4 to 12. A method according to claim 1 wherein the disaccharide is as defined in claim 5. The use of a composition as defined in any of claims 3 to 12 in the promotion of mammalian hair growth or regrowth. The use of a disaccharide as defined in any of claims 1 to 5 in the preparation of a composition for the treatment of baldness.

Inventors: COUCHMAN, JOHN ROBERT THE DIABETES RES. & TRAIN., GIBSON, WALTER THOMAS, Couchman, John Robert The Diabetes Res. &amp; Train.
Applicants: UNILEVER N.V., UNILEVER PLC
Application year: 1986
Main classification: A61K7
IPC codes: A61K8, A61K31, C07H11, A61Q5, A61P17, C07H3, C07H13, A61Q7, C07H15, C07H7