GB2572322A - A hair treatment composition - Google Patents

Abstract

A hair treatment composition comprising L-fucose and chondroitin disaccharide, and is formulated for topical application to the hair, or skin where hair is growing, or formulated for oral administration. The hair treatment composition is for treating hair to improve the condition, quality or composition of the hair.

Description

A hair treatment composition

Field of the Invention

The present invention relates to a hair treatment composition. Also contemplated are methods of treating hair with a composition to promote hair growth, prevent hair loss, and improve the condition, composition or quality of hair.

Background to the Invention

There is a lack of information about L-fucose influence on hair condition. This is a very important issue when it is considered that more and more people every year suffer because of poor hair condition and hair loss. Natural dynamics of the hair growth process, occurs through three phases known as: anagen (growth phase included about 85% of hairs, last from 2 to 7 years), catagen (transitional phase lasting up to 2 weeks) and telogen (resting phase which last from 1 to 4 months), can be impaired by a number of factors, such as genetic predisposition, hormonal disorders, aging, as well as poor nutrition or stress.

The hair follicle is considered to be a mini-organ with a plethora of different cell types which co-ordinate the hair growth cycle through a complex cascade of signalling pathways. Crucial element in the hair follicles for maintaining normal hair growth cycle are mesenchymal derived Dermal Papilla Cells (DPC). The task performed by these cells during the hair growth cycle makes them an excellent model for in vitro evaluation of molecules with hair growth promoting properties. Manipulating the course of hair growth cycle comprises the basic therapeutic strategy for all type of hair loss. Hair growth promoting products should induce or prolong the anagen phase, induce anagen in telogen phase follicles, inhibit catagen as well as inhibit of exogen (shedding phase of hair cycle). Targeting of the anagen phase is a favoured strategy as it enables targeting of the induction of new hair follicle formation and / or prolonging the duration and rate of hair growth. The key biomarkers of the anagen phase of the hair cell cycle is an increase in Dermal Papilla

Cells proliferation, an increase in alkaline phosphatase activity levels and expression of growth factors such as insulin growth factor. Currently used therapeutic agents, Minoxidil and Finasteride, are not effective treatment tool in all cases of hair loss. Furthermore, their effectiveness is less when used alone and they can cause unwanted side effects.

Summary of the Invention

The present invention addresses the need for a hair treatment/growth composition by providing a composition formulated for administration to a subject and that contains effective amounts of chondroitin disaccharide and L-fucose. The composition may be formulated for topical or oral administration, or for other methods of administration. The combination of these components has been found to have a synergistic effect in increasing the alkaline phosphatase activity levels in primary human follicle dermal papilla cells (a marker of growth / anagen phase of the hair cycle), compared with treatment with the individual components (Example 4 and Table 2). In addition, simultaneous treatment of primary human follicle dermal papilla cells with L-fucose and Chondroitin disaccharide Δdi 4S sodium salt caused an increase in dermal papilla cell proliferation (Example 1 and Fig. 1)

According to a first aspect of the present invention, there is provided a composition comprising L-fucose and/or chondroitin disaccharide. Preferably, the composition comprises an effective amount of L-fucose and an effective amount of chondroitin disaccharide.

In one embodiment, the composition is formulated for topical administration (topical composition).

In one embodiment, the composition is formulated for oral delivery (oral composition).

In one embodiment, the composition comprises 1.0 to 0.005 % L-fucose (w/v) and 0.1 to 0.00001 % chondroitin disaccharide (w/v).

In one embodiment, the composition comprises 0.5 to 0.005 % L-fucose (w/v).

In one embodiment, the composition comprises 0.1 to 0.01 % L-fucose (w/v).

In one embodiment, the composition comprises 0.05 to 0.00005 % chondroitin disaccharide (w/v).

In one embodiment, the composition comprises 0.01 to 0.0001 % chondroitin disaccharide (w/v).

In one embodiment, the composition comprises 0.5 to 0.005 % L-fucose (w/v) and 0.05 to 0.00005 % chondroitin disaccharide (w/v).

In one embodiment, the composition comprises 0.1 to 0.01 % L-fucose (w/v) and 0.01 to 0.0001 % chondroitin disaccharide (w/v).

In one embodiment, the topical composition is selected from a gel, cream, ointment or lotion. In one embodiment, the topical composition is selected from a shampoo, conditioner or shower/body gel.

In one embodiment, the composition is formulated for oral delivery, and is typically provided in the form of unit dose product, for example a tablet, nutraceutical tablet, capsule, sachet, beverage, or food product.

In one embodiment, the L-fucose is derived from a marine algae. In one embodiment, the Lfucose is derived from a seaweed. In one embodiment, the seaweed is selected from the range of brown Phaeophyceae, alage and certain sea animals such as sea cucumbers and sea urchins.

L-Fucose may also be produced via biotechnological processes or via extraction from other plant, fruit, vegetable and fungi species such as mushrooms, tomatoes and various seeds.

In one embodiment, the chondroitin disaccharide is derived from a marine, animal or Avians or Invertebrate species. In one embodiment, the chondroitin disaccharide is derived from a bone, shell, cartilage, skin, intestine or other GAG and proteoglycan rich materials

In one embodiment, the chondroitin disaccharide is chondroitin disaccharide salt. In one embodiment, the chondroitin disaccharide salt is chondroitin disaccharide Adi-4S sodium salt

In one embodiment, the topical composition comprises one or more cosmetically acceptable excipients.

In one embodiment, the oral composition comprises one or more nutritional or nutraceutical components.

In another aspect, the invention provides a method of treating a mammal to improve the growth or condition, or inhibit loss, of the mammals’ hair, the method comprising a step of administration of an effective amount of the composition of the invention to the mammal.

In one embodiment, the composition is a topical composition and the method comprises topical administration of the composition it is generally applied to the skin where the hair grows, usually the scalp, but it may also be applied to the face, neck, chest, back, legs or arms.

In a preferred embodiment, the topical composition is topically applied to a scalp of the mammal.

In one preferred embodiment, the topical composition is applied every 5-10 days, for example every 5, 6, 7, 8, 9 or 10 days.

In one embodiment, the composition is not washed off once applied for a period of at least 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96 or 108 hours.

In another embodiment, the composition is formulated for oral administration, and is orally administered to the mammal.

In one embodiment, the oral composition is administered daily.

In one embodiment the oral composition is administered as a regimen over a 30 day period, which can involve a range of days between administrations from 1 - 30 or any combination thereof

In one embodiment, the oral composition is administered once or several times a day, or every 2-30 days, for a period of time until the composition is effective.

In one embodiment the treatment is a combination or oral and topical involving administration of frequencies of daily for any period of 1 to 31 days and any repeating combination thereof over a 6-month period,

Other aspects and preferred embodiments of the invention are defined and described in the other claims set out below.

Brief Description of the Figures

Figure 1: Effect of simultaneous treatment with L-fucose and Chondroitin disaccharide Δdi 4S sodium salt on proliferation in Dermal Papilla Cells.

Figure 2. Alkaline Phosphatase Activity Levels in Primary Dermal Papilla Cells following treatment with L-Fucose. HDFC cells were treated with L-Fucose at 0.1 - 0.001 w/v for up to 168 hours with alkaline phosphatase activity levels evaluated at 72, 120 & 168 hours post treatment. The largest increase was observed at 168 hrs post treatment with 0.001% w/v LFucose.

Figure 3. Effect of Chondroitin disaccharide Adi-4S sodium salt on Alkaline Phosphatase expression in primary Human Follicle Dermal Papilla Cells. HDFC cells were treated with

Chondroitin Disaccharide at 0.1 - 0.0001 w/v for up to 168 hour with alkaline phosphatase activity levels evaluated at 72, 120 & 168 hours post treatment. The largest increase was observed with a 128% increase at 168 hrs post treatment with 0.01% w/v Chondroitin Disaccharide.

Figure 4: Alkaline Phosphatase Activity Levels in primary dermal papilla cells in response to L-Fucose, Chondrotin Disaccharide co-treatment. Alkaline Phosphatase activity levels significantly increased following co-treatment with L-Fucose, Chondroitin Disaccharide and co-treatments with L-Fucose, Chondroitin Disaccharide. A statistically significant increase was detected at all concentrations. The largest increase was elicited by 0.1% w/v L-fucose + 0.001% w/v CS (+192%) and 0.01% w/v L-fucose + 0.0001% w/v CS (+171%) at 168 hours post treatment.

Detailed Description of the Invention

All publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full.

Definitions and general preferences

Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:

Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term a or an used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms a (or an), one or more, and at least one are used interchangeably herein.

As used herein, the term comprise, or variations thereof such as comprises or comprising, are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method/process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method/process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term comprising is inclusive or open-ended and does not exclude additional, unrecited integers or method/process steps.

As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.

As used herein, the term treatment or treating refers to an intervention (e.g. the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s) (for example, the reduction in accumulation of pathological levels of lysosomal enzymes). In this case, the term is used synonymously with the term “therapy”. Additionally, the terms treatment or treating refers to an intervention (e.g. the administration of an agent to a subject) which prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence within a treated population. In this case, the term treatment is used synonymously with the term “prophylaxis”. In the context of hair, the term “treatment” generally refers a treatment that results in one or more of improvement in hair growth (increasing the rate of grow th, or density of growth, or both), or slowing or inhibiting hair loss, or improving the condition of hair, including , composition and/or quality of hair.

As used herein, an effective amount or a therapeutically effective amount as applied to the active agents (chondroitin disaccharide and L-fucose) means amounts which effect an increase in hair growth, an improvement of hair condition, including composition and/or quality of hair, or decrease in hair loss. Generally, and effective amount means 1.0 to 0.005 % L-fucose (w/v) and 0.1 to 0.00001 % chondroitin disaccharide (w/v).

In the context of treatment and effective amounts as defined above, the term subject (which is to be read to include individual, animal, patient or mammal where context permits) defines any subject, particularly a mammalian subject, for whom treatment is indicated. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; and rodents such as mice, rats, hamsters and guinea pigs. In preferred embodiments, the subject is a human.

As used herein, the term “condition characterised by excessive hair loss of impaired hair growth” refers to a medical condition that manifests in excessive hair loss or impaired hair growth. Examples of such conditions include alopecia, traction alopecia, alopecia areata, androgenetic or androgenic alopecia, tinea capitis, telogen effluvium, scalp infections, diseases that cause scarring alopecia, hair pulling disorders, and conditions associated with hormonal disorders such as pregnancy, childbirth, menopause.

As used herein, the term “topical composition” refers to a composition that is formulated for topical administration. “Topical administration” refers to the application to the keratinous tissue, such as the hair and areas of the skin where hair grows. In particular, formulations for topical delivery are described in Topical drug delivery formulations edited by David Osborne and Antonio Aman, Taylor & Francis, the complete contents of which are incorporated herein by reference. An alternative means of topical administration is transdermal administration, for example by use of a skin patch. For example, the active ingredient can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycols or liquid paraffin. Compositions may be formulated in unit dosage form, i.e., in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose.

As used herein, the term “cosmetic composition” when used herein relates to a composition that can be used for cosmetic purposes, personal care and/or hygiene purposes. It will be appreciated that the composition may have more than one cosmetic purpose and may be used for more than one of these purposes at the same time. The cosmetic composition may be in the form of a hair treatment composition such as a shampoo or conditioner.

As used herein, the term “composition formulated for oral administration” or “oral composition” means a composition that is suitable for ingestion by a mammal. The composition may be a pharmaceutical composition and include one or more pharmaceutically acceptable excipients, or it may be a food, beverage, food ingredient, or food supplement. In one embodiment, the composition is provided in the form of a unit dose product, and may be in the form of a tablet, capsule, pill, ampoule, sachet, or any other unit dose form.

As used herein, the term “chondroitin disaccharide” refers to a disaccharide unit composed of glucuronic (GlcA) and N-acetylgalactosamine (GalNAc), or a cosmetically pharmaceutically acceptable salt of the disaccharide. The disaccharide is generally derived from the sulphated glycosaminoglycan, chondroitin sulphate (CS), and usually contains sulphate residues at various positions in the disaccharide molecule. Proteoglycans containing chondroitin sulphate are ubiquitous in nature and can be found in connective tissue matrix, cell surface and basement membranes, intracellular granules of certain cells, plant tissue and seaweeds. Chondroitin disaccharide may be provided as a free base or a salt. Examples of specific chondroitin disaccharides include chondroitin disaccharide Adi4S sodium salt (Sigma Aldrich); chondroitin disaccharide Adi-US-2S sodium salt (Sigma Aldrich); chondroitin disaccharide 5di-6S sodium salt (Santa Cruz Biotechnology); chondroitin disaccharide 6di-4S sodium salt (Creative-Enzymes); chondroitin disaccharide di-OS sodium salt (Carbosynth.com). In one embodiment, the chondroitin disaccharide is derived from a natural source from plant or animal, marine or terrestrial sources. In one embodiment, the chondroitin disaccharide is derived from a marine algae source. . Examples of chondroitin disaccharidesinclude chondroitin disaccharide Adi-4S sodium salt (Sigma Aldrich), and chondroitin disaccharide Adi-US-2S sodium salt (Sigma Aldrich).

Chondroitin disaccharides may be obtained from commercial sources (as described above), or may be extracted from natural products by extracting chondroitin sulphate from the natural source using CS digesting enzymes (for example a CS digesting enzyme derived from Sphingomonas paucimobHis. a non-fermenting Gram-negative bacillus cultured in the lab) to digest CS and generate a crude CS oligosaccharide preparation, and then fractionating the oligosaccharides by gel filtration chromatography to provide the CS disaccharide preparation. They can also be released via microbial fermentation of large Chondroitin Sulphate polysaccharides. Chondroitin disaccharides are described in the following publications: Kale et al. (Mar Biotechnol (NY) 2015: Aug;17(4)); Flengsrud et al. (Glycoconj J. 2016 Apr;33(2)), and Faller et al. (J Phys Chem B 2015 May 21:119(20)).

As used herein, the term “L-fucose” refers to a hexose deoxy sugar that exists in nature in the L-configuration (and which lacks a hydroxyl group on the carbon at the six position hence deoxy) or a cosmetically pharmaceutically acceptable salt thereof. It is found in nature on N-linked glycans in a wide variety of organisms, including mammal, insect and plant cell surfaces. In one embodiment, the L-fucose is derived from a natural source. In one embodiment, the L-fucose is derived from a marine algae source, preferably seaweed. Examples of L-fucose derived from seaweed include L-(-)-Fucose (Sigma Aldrich F2252). L-fucose is described in the following articles: Becket et al. (Glycobiology 2003 13(7); Ale et al. (Marine Drugs 2011 (Nov)); and Gerber et al (The New Phytrologist 2014 (June). Fucose can be released from fucose containing polymers by an enzyme called afucosidase. L-Fucose may also be produced via biotechnological processes or via extraction from other plant, fruit, vegetable and fungi species such as mushrooms, tomatoes, brewers yeast and various seeds.

As used herein, the term “actives” refers to chondroitin disaccharide and L-fucose.

The term “cosmetically or pharmaceutically acceptable salt” means a salt recognized for its use in animals and more specifically in human beings, and includes salts used to form base addition salts, either they are inorganic, such as and not restricted to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminium among others, either they are organic, such as and not restricted to, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine among others, or acid addition salts, either they are organic, such as and not restricted to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate or gluconate among others, or inorganic, such as and not restricted to, chloride, sulfate, borate or carbonate, among others. The nature of the salt is not critical, provided that it is cosmetically or pharmaceutically acceptable. The cosmetically or pharmaceutically acceptable salts of the actives of the invention can be obtained by the conventional methods, well known in the prior art.

The topical composition of the invention may be presented in a formulation selected from the group comprising creams, multiple emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydro-alcoholic solutions, hydro-glycolic solutions, cosmetic, personal care product, hydrogels, liniments, sera, soaps, dusting powder, paste, semi solid formulations, liniments, serums, shampoo, conditioner, ointments, any rinse off formulation, talc, mousses, powders, sprays, aerosols, solutions, suspensions, emulsions, syrups, elixirs, polysaccharide films, patches, gel patches, bandages, an adhesive system, water-in-oil emulsions, oil-in-water emulsions, and silicone emulsions.

In an embodiment of the current invention, the emulsion contains a lipid or oil. The emulsion may be, but is not limited to, oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silcone emulsions. The emulsion may contain a humectant. The emulsion may contain an anti-foaming agent, such as silicone. The emulsion may have any suitable viscosity. Emulsions may further contain an emulsifier and/or an anti-foaming agent. Methods of preparing an emulsion are known to a person skilled in the art.

The topical composition of the invention may be incorporated into a medical device for administration. Such a device can include but is not limited to a fabric, patch, bandage, gauge, sock, tight, underwear, dressing, glove, mask, adhesive patches, non-adhesive patches, occlusive patches and microelectric patches or suitable adhesive system. In such an embodiment, the device is in direct contact with the keratinous layer such as the skin, thus releasing the actives of the invention. It will be understood that the topical composition may be incorporated in any suitable form as detailed herein. For example, the topical composition of the invention can be incorporated into the device or be present on the surface of the device or can be in a cream, gel or wax formulation or any suitable formulation defined herein and incorporated into the device or on the surface of the device.

The device may be adapted for adhesion or attachment to the skin from which hair is growing.

In one embodiment the device is adapted to release a constant quantity of the composition of the invention. It will be understood that the amount of the composition contained in the sustained release system will depend, for example, on where the composition is to be administered, the kinetics and duration of the release of the composition of the invention, as well as the nature of the condition, disorder and/or disease to be treated and/or cared for. The device may be such that the composition is released by biodegradation of the device, or by friction between the device and the body, due to bodily moisture, the skin's pH or body temperature.

In an embodiment of the invention the topical composition may further comprise at least one cosmetically acceptable excipient. Excipient may be used interchangeably with functional ingredient or additive. It will be understood that although the topical compositions of the current invention can be administered alone, they will generally be administered in admixture with a cosmetic excipient. Cosmetically acceptable excipients are well known in the art and any known excipient, may be used provided that it is suitable for topical administration and is dermatologically acceptable without undue toxicity, incompatibility and/or allergic reaction. The amount of excipient included will depend on numerous factors, including the type of excipient used, the nature of the excipient, the component(s) of the topical composition, the amount of active in the topical composition and/or the intended use of the topical composition. The nature and amount of any excipient should not unacceptably alter the benefits of the actives of this invention. In an embodiment of the invention the excipient may be a suitable diluent, carrier, binder, lubricant, suspending agent, coating agent, preservative, stabilisers, dyes, vehicle, solubilising agent, base, emollient, emulsifying agent, fragrance, humectant, and/or surfactants. Examples of suitable diluents include, but are not limited to, any diluent disclosed in disclosed in US2014120131 or US2004132667. Examples include ethanol, glycerol and water. Examples of suitable carriers include, but are not limited to, lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and any suitable carrier disclosed in US2014120131 or US2004132667. Examples of suitable binders include, but are not limited to, starch, gelatin, glycerine, natural sugars such as glucose, anhydrous lactose, freeflow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol and any suitable binder disclosed in US2014120131 or US2004132667. Examples of suitable lubricants include, but are not limited to, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride and any suitable lubricant disclosed in US2014120131 or US2004132667.

The carrier may be any suitable carried known in the art or disclosed in US2014120131 or US2004132667. In some embodiments, the carrier may include, but is not limited to, a liquid, such as water, oils or surfactants, including those of petroleum, animal, plant or synthetic origin, polymer, oil, such as peanut oil, mineral oil, castor oil, soybean oil, alcohol, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxynols, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, or digitonin. It will be understood that the carrier will be dermatologically acceptable. Preferred carriers contain an emulsion such as oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silicone emulsions. Emulsions may further contain an emulsifier and/or an anti-foaming agent.

In an embodiment of the invention, the topical composition may further comprise one or more additional ingredients. The topical composition of the invention may be administered consecutively, simultaneously or sequentially with the one or more other additional agents. Such additional ingredients may be those of benefit to include in a topical composition, or of benefit depending on the intended use of the topical composition. The additional ingredient may be active or functional or both.

Examples of such additional ingredients include, but are not limited to, one or more of cleaning agents, conditioning agents, sunscreen, pigment, moisturiser, thickening agents, gelling agents, essential oil, astringents, pigments, anti-caking agent, anti-foaming agent, binders, additives, buffers, chelating agents, external analgesics, film formers or materials, bulking agents, polymers, opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin bleaching and lightening agents, skin conditioning agents, aloe vera, healing agents, soothing agents, smoothing agents, pantothenic acid, treating agents, thickeners, vitamins, colourants, pharmaceuticals, antiseptic agents, antifoaming agents, buffering agents, astringents, polymers, pH adjuster, deodorant or any other dermatologically acceptable carrier or surfactant.

It is to be understood that additional ingredients listed may provide more than one benefit. The classification given herein is for clarity and convenience only and not intended to limit the additional ingredient to that particular application or category listed.

The topical composition may be alcohol free.

In some embodiments of the invention, the composition further comprises one or more additional active agents, in addition to the actives of the composition. In addition, or alternatively, the composition may be administered with one or more other additional active agents. Typical said additional active agent is present in trace amounts only. In some embodiments, there may be no additional active agent present in the composition. The amount of additional active agent included will depend on numerous factors, including the type of additional active agent used, the nature of the additional active agent, the components) of the topical composition, the amount of active in the topical composition and/or the intended use of the topical composition. The nature and amount of any additional active agent should not unacceptably alter the benefits of the actives of this invention. It is to be understood that an ingredient that is considered to be an “active” ingredient in one product may be a “functional” or “excipient” ingredient in another and vice versa. It will also be appreciated that some ingredients play a dual role as both an active ingredient and as a functional or excipient ingredient. Examples of the additional active agents include glucose transport promoting drugs, skin supplement, agent for treatment and/or care of the skin, anti-inflammatory agent, an anti-aging agent, a cellular growth promoting agent and pharmacological enhancers. Such agents are well known in the art and it will be appreciated that any suitable additional active agent may be used. Additional active agents for treatment and/or care of the skin may include collagen synthesis agents, retinoids, exfoliating agents, anti-cellulite agents, elastase inhibiting agents, melanin synthesis stimulating or inhibiting agents, self-tanning agents, antiaging agents, antimicrobial agents, antifungal agents, fungistatic agents, bactericidal agents, and healing agents. Active agents also include antiinflammatory agents. Any additional active agent should be suitable for application to the skin without undue toxicity, incompatibility and/or allergic reaction. It will be understood that the classification given herein is for clarity and convenience only and not intended to limit the additional ingredient, excipient, or active to that particular application or category listed.

In a particularly preferred embodiment, the methods and uses of the invention involve administration of a composition of the invention in combination with one or more other active agents, for example, existing growth promoting drugs or pharmacological enhancers available on the market. In such cases, the compounds of the invention may be administered consecutively, simultaneously or sequentially with the one or more other active agents.

The topical composition of the invention is administered in a cosmetically or pharmaceutically effective amount. In other words, in an amount that is non-toxic but sufficient amount to provide the desired effect such as improved hair growth, inhibited hair loss, or improvement of hair condition. It will be appreciated that a person skilled in the art would be capable of determining an appropriate dose of the topical compositions of the invention to administer without undue experimentation. Alternatively, a physician will determine the actual dose that is most suitable for a patient depending on the particular condition, disease or disorder to be treated or cared for and the age, body weight and/or health of the person. It will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. There can, of course, be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. The amount and the frequency is as best suited to the purpose. The frequency of application or administration can vary greatly, depending on the needs of each subject, with a recommendation of an application or administration range from once a month to ten times a day, preferably from once a week to four times a day, more preferably from three times a week to three times a day, even more preferably once or twice a day.

In preferred embodiments, repeated use of the topical composition is provided.

The topical composition may be applied by, but not limited to, rubbing, or massaging into the hair or skin where hair grows to be treated or cared for. In some embodiments, the composition is left on or not removed from the area of the body. In some embodiments of the current invention, the composition of the invention may be applied to an area to be treated by means to achieve a greater penetration of the composition of the invention, such as, but not limited to, iontophoresis, sonophoresis, electroporation, microelectric patches, mechanical pressure, osmotic pressure gradient, occlusive cure, microinjections or needlefree injections by means of pressure, such as injections by oxygen pressure, or any combination thereof

In some embodiments of the current invention, the composition (particularly oral compositions) may be delivered via any one of liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, millicapsules, capsules, macrocapsules, nanocapsules, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactant-phospholipid mixed micelles, millispheres, spheres, lipospheres, particles, nanospheres, nanoparticles,milliparticles, solid nanopartciles as well as microemulsions including water-in-oil microemulsions with an internal structure of reverse micelle and nanoemulsions microspheres, microparticles.

A variety of methods are available for preparing liposomes. See, e.g., Szoka et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871, 4,261,975, 4,485,054, 4,501,728, 4,774,085, 4,837,028, 4,235,871, 4,261,975, 4,485,054, 4,501,728, 4,774,085, 4,837,028, 4,946,787, PCT Publication No. WO 91/17424, Deamer &

Bangham, Biochim. Biophys. Acta 443:629-634 (1976); Fraley, et al., PNAS 76:3348-3352 (1979); Hope et al., Biochim. Biophys. Acta 812:55-65 (1985); Mayer et al., Biochim. Biophys. Acta 858:161-168 (1986); Williams et al., PNAS 85:242-246 (1988); Liposomes (Ostro (ed.), 1983, Chapter 1); Hope et al., Chem. Phys. Lip. 40:89 (1986); Gregoriadis, Liposome Technology (1984) and Lasic, Liposomes: from Physics to Applications (1993)). Suitable methods include, for example, sonication, extrusion, high pressure/homogenization, microfluidization, detergent dialysis, calcium-induced fusion of small liposome vehicles and ether fusion methods, all of which are well known in the art.

These delivery systems may be adapted to achieve a greater penetration of the composition of the invention. This may improve pharmacokinetic and pharmacodynamics properties. The delivery system may be a sustained release system wherein the composition of the invention is gradually released during a period of time and preferably with a constant release rate over a period of time. The delivery' systems are prepared by methods known in the art. The amount of active contained in the sustained release system will depend on where the composition is to be delivered and the duration of the release as well as the type of the condition, disease and/or disorder to be treated or cared for.

The topical composition of the invention may be for human or animal usage in human and veterinary medicine.

As used herein, the term “personal care product” should be understood to mean a composition formulated for use by humans in cleaning or treating the human body, particularly the skin and hair. Examples include shampoo, conditioner, skin creams and lotions, powders, dentifrice, shower gel or creams, bath or shower gel, hair dye, soap, body scrub, exfoliant, anti-dandruff solutions body lotion, moisturisers, cleaners, masks, oils, serums, and rinses.

As used herein, the term dermatologically acceptable, means that the topical composition(s) or component(s) of the composition(s) are suitable for use in contact with human skin without risk of toxicity, incompatibility, instability and/or allergic response, and similar.

Various delivery systems are known and can be used to administer the composition of the invention, e.g., encapsulation in liposomes, microparticles, microcapsules. Methods of introduction include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. The compounds or compositions may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. In addition, it may be desirable to introduce the compounds or compositions of the invention into the circulation system by any suitable route. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent.

Alternatively, the compounds can be delivered in a vesicle, in particular a liposome (see Langer, Science, 1990, 249, 1527-1533; Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353365 (1989); Lopez-Berestein, ibid., pp. 317-327).

In yet another embodiment, the compounds or compositions of the invention can be delivered in a controlled release system. In one embodiment, a pump may be used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng., 1987, 14, 201; Buchwald et al., Surgery, 1980, 88, 75; Saudek et al., N. Engl. J. Med., 1989, 321, 574). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Press., Boca Raton, Fla. (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, J. Macromol. Sci. Rev. Macromol. Chem., 1983, 23, 61; see also Levy et al., Science, 1985, 228, 190; During et al., Ann. Neurol., 1989, 25, 351; Howard et al., J. Neurosurg., 1989, 71, 105). In yet another embodiment, a controlled release system can be placed in proximity of the therapeutic target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled release systems are discussed in the review by Langer (Science, 1990, 249, 1527-1533).

The present invention also provides pharmaceutical compositions. Such compositions comprise an effective amount of L-fucose and chondroitin disaccharide, and a pharmaceutically acceptable excipient or carrier. In a specific embodiment, the term pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals and more particularly in humans.

The term excipient refers to a diluent, adjuvant, excipient, or vehicle with which the compound or pro-drug of the invention is administered. Such pharmaceutical excipients can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol and water.

Exemplification

The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention.

EXAMPLE 1: Effect of L-fucose and chondroitin disaccharide on DPC proliferation.

Dermal Papilla Cells were seeded at a density of 10,000 cells per well in 96-well plates in 100 μΐ of complete media. Cells were allowed to adhere overnight.

Treatment media was prepared containing appropriate concentration of L-fucose

0.1% w/v L-fucose

0.01% w/v L-fucose

0.001% w/v L-fucose

0.0001% w/v L-fucose

Treatment media was prepared containing appropriate concentration of chondroitin disaccharide Δ di-4S sodium salt: 0.01% w/v chondroitin disaccharide 0.001% w/v chondroitin disaccharide 0.0001% w/v chondroitin disaccharide

Treatment media was prepared containing appropriate concentration of L-fucose and chondroitin disaccharide Δ di-4S sodium salt:

1% w/v L-fucose + 0.01% w/v chondroitin disaccharide

1% w/v L-fucose + 0.001% w/v chondroitin di saccharide

1% w/v L-fucose + 0.0001% w/v chondroitin disaccharide

0.1% w/v L-fucose + 0.01% w/v chondroitin disaccharide

0.1% w/v L-fucose + 0.001% w/v chondroitin disaccharide

0.1% w/v L-fucose + 0.0001% w/v chondroitin disaccharide

0.01% w/v L-fucose + 0.01% w/v chondroitin disaccharide

0.01% w/v L-fucose + 0.001% w/v chondroitin disaccharide

0.01% w/v L-fucose + 0.0001% w/v chondroitin disaccharide

Treatments were performed in triplicate wells. Cells were cultured for a further 24, 48 and 72 hours. No media changes were performed between initial treatment and cell assays. Media only was used to treat controls cells. An additional control was used to assess the impact of solvent (H2O Control). After exposure for the desired period of time 11 pl PrestoBlue reagent was added to each well of the 96-well plate. Plates were incubated in the dark for 2 hrs at 37°C. Fluorescence was read using a 560 nm excitation/590 nm emission filter set (lOnm bandwidth). Fluorescence data in wells containing cells were corrected for background fluorescence using cell free media control replicates.

EXAMPLE 2: Effect of L-fucose and chondroitin disaccharide on Alkaline Phosphatase expression in DPC.

The SensoLyte Alkaline Phosphatase assay comprises of p-nitrophenyl phosphate (pNPP) which is substrate for enzyme. Upon dephosphorylation, pNPP turns yellow and can be detected at absorbance = 405nm. Alkaline Phosphatase concentration is calculated according to the standard curve using serial dilutions f enzyme standards. Cells were seeded in transparent 12-well plates at density 30,000 cells per well in 2 ml complete media. Cells were allowed to adhere overnight.

Treatment media was prepared containing appropriate concentration of 1) L-fucose, 2) chondroitin di saccharide and 3) L-fucose + chondroitin di saccharide Δ di-4S sodium salt as described above:

Cells were assessed for AP expression at 72, 120 and 168 hours. Cells were gently washed twice with IX assay buffer. Triton X-100 was added to IX assay buffer and lysis buffer was added to each well. Cells were transferred into eppendorf tubes and subjected to 3 freeze thaws to ensure cells lysis. Cell suspensions were centrifuged at 2500g for 10 min at 4°C. Supernatants were used to AP assay.

A 2-fold serial dilution of calf AP standard was resulting in concentrations of 100, 50, 25, 12.5, 6.2, 3.1, and 0 ng/ml AP solutions. 50 pl of each standard dilution and each lysate sample was added in triplicate to a 96-well plate. To this, 50 pl of pNPP substrate solution was added and the reagents were mixed by gently shaking for 30 seconds. The plate was incubated at 37°C for 60 minutes. Absorbance was read using a VarioSkan Plate reader programmed to read absorbance at 405 nm.

EXAMPLE 3: L-fucose and chondroitin disaccharide effect on Dermal Papilla Cells proliferation.

Treatment with L-fucose and chondroitin sulphate independently or in combination caused a statistically significant increase in cell proliferation. Maximum cell proliferation rates observed were, 18.98% for L-Fucose (0.01% at 24 hours), 28.76% for Chnrodrotin Sulphate (0.01w/v at 24h hours) and 20.78% for the co-treatment, at 24 hours post treatMent with Είπε 0.1 % + CS dis 0.001%., Figure 1 and Table 1.

Statistical significance of the differences in mean values was assessed using one-way

ANOVA followed by Dunnett's multiple comparison test.

* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001

Table 1. Dermal Papilla Cell Proliferation. Treatment of dermal papilla cells with L-Fucose,

Chondroitin Disaccharide and the co-treatment L-Fucose, Chondroitin Disaccharide resulted in a significant increase in dermal papilla cell proliferation. Data on treating cells with only L-Fucose or

Chondroitin Disaccharide is included for comparison.

Product	24 hours	48 hours	72 hours
L-fucose 1 % w/v		I5.18±
	life	1.21****
L-fucose 0.1% w/v	18.65 ±	| 16.17 1	i 11.41 ±1.20**

**** i i 75****

L-fucose 0.01% w/v	18.98 ± |	! 11.85 ±2.83***
L-fucose 0.001% w/v	11.71 ± 1 39****	12.26 ± 1.60***	] 11.93 ± 1.79*** !
Chondroitin disaccharide 0.01%	28.76 ±	25.64 ±	i 17.79 1
i w/v j	2.22****	| 2.34****	[ 1.00****
Chondroitin disaccharide 0.001%	18.22 ±	18.57 ±	1 12.49 ± 1.71*** !
w/v i	1 2i****	ί 1 85****
i Chondroitin disaccharide 0.0001% i	15.12 ±	16.31 ±	j 14.45 ±
iiiie	2.09****	2.10****	llllO

L-fuc 0.1 % + CS dis 0.01%	i 20.42 ±	i 21.54±	i 9.51 ±0.65** !
	; | 25****	; i 64^	i :
L-fuc 0.1 % + CS dis 0.001 %	IBM	17.81 ±
	3.19****	4 52****
I .-flic 0.1 % + CS dis 0.0001 %	ί 1 1.94 ±0.88***	; 12.19 ± |.2I***	; 13.49 ±4.36*** ;
L-fuc 0.01 % + CS dis 0.01%	17.51 ±	19,08±	ΐ 12.69 ±1.32*** ί
	1.04****	0.98****
L-fuc 0.01 % + CS dis 0.001%	; 18.02 ±	12.76 ± 4.11***	| 9.05 : i.66* !
	i 1 76****	:	: :
L-fuc 0.01 % + CS dis 0.0001 %	ί 10.21 ±1.48**	; 12.01 ±1.32**	i 4.70 ± 1.57

EXAMPLE 4: L-fucose, chondroitin disaccharide and co-treatments effect on Alkaline

Phosphatase Activity:

Treatment of Human Primary Dermal Papilla Cells with L-Fucose:

cells were treated with 3 concentrations of L-Fucose, 0.1%, 0.01% and 0.001% w/v with Alkaline Phosphatase activity level evaluated at 72, 120 & 168 hours post treatment. All treatments resulted in statistically significant increase in Alkaline Phosphatase production in response to all used concentrations Figure. 2 and Table 2, activity levels were increased at all concentrations 24 hours post treatment (38 - 50%) further increasing in a concentration dependent manner to between 65 - 88 % by 168 hours post treatment.

The results are expressed as a percentage of control from three independent experiments. Statistical significance of the differences in mean values was assessed using one-way ANOVA followed by Dunnett's multiple comparison test.

0.0001

Treatment of Human Primary Dermal Papilla Cells with Chondroitin Disaccharide: cells were treated with 3 concentrations of Chondroitin Disaccaride 0.01%, 0.001% and 0.0001% w/v. Alkaline Phosphatase activity levels were evaluated at 72, 120 & 168 hours post treatment. A statistically significant increase in Alkaline Phosphatase production in response to all used concentrations at all-time points. Figure. 3 and Table 2 from (38 - 43%) at 72 hours post treatment further increasing in a concentration dependent manner, with the largest increase of 128% in response to 0.01% w/v at 168 hours post treatment.

The results are expressed as a percentage of control from three independent experiments. Statistical significance of the differences in mean values was assessed using one-way ANOVA followed by Dunnett's multiple comparison test.

**** p _< 0.0001

Treatment of Human Primary Dermal Papilla Cells with L-Fucose & Chondroitin Disaccharide:

Cells were co-treated with L-Fucose (0.1% - 0.001 w/v & and Chondroitin Disaccharide (0.0001%) with Alkaline Phosphatase activity levels evaluated at 72, 120 & 168 hours post treatment, see Figure 4 and Table 2.

Table 2: Alkaline Phosphatase Activity Levels in dermal papilla cells in response to LFucose, Chondroitin Disaccharide co-treatments. Alkaline Phosphatase activity levels significantly increased following treatment with L-Fucose, Chondroitin Disaccharide and co-treatments with L-Fucose & Chondroitin Disaccharide. A statistically significant increase was detected at all concentrations. The largest increase was elicited by 0.1% w/v Lfucose + 0.001% w/v CS and 0.01% w/v L-fucose + 0.0001% w/v CS at 168 hours post treatment. Data on treating cells with only L-Fucose or Chondroitin Disaccharide is included for comparison.

Product	72 hours	120 hours	168 hours
L-fucose 0.1% w/v	38.89 + 3.42****	65.82 + 6.18****
L-fucose 0.01% w/v	50.59 + 3.27****	i 64.83 + 2.34****	i 69.83 + 4.36****
L-fucose 0.001 % w/v	45.53 ± 3.52****		ί 88.26 + 3.96****
Chondroitin disaccharide	383Ϊ'±'5Α9***	P 36 77 ± 2'91***	Ί 128.03 -
0.01% w/v			ί 4 79****
Chondroitin disaccharide	44.11 ±6.00****	ί 44.77+3.67****	1 85.80 + 7.26****
0.001% w/v
Chondroitin disaccharide	43.93 ± 6.01****	i 69.85 + 5.66****	i 94.92 + 7.20****
0.0001% w/v
L-fuc 0.1 % + CS dis 0.01 %	41.70+ 7.43*	i 39.03 ± 4.32*	144.52 + 14.16****
L-fuc 0.1 % + CS dis 0.001%	49.21 + 6.63**	57.26 + 5.27***	i 168.03 ± i 13.35****
L-fuc 0.1 % + CS dis 0.0001 %	43.87+ 7.00*	37.74 + 4.31*	152.82 +
			12.10****
L-fuc 0.01 % + CS dis 0.01%	41.02 + 7.17*	i 42.84 + 3.43*	i 192.25 ±
			ί 14 99****
L-fuc 0.01 % + CS dis 0.001 %	30.73 ± 3.55	ί 44.34 + 3.91**	143.70 + 5.05****
L-fuc 0.01 % + CS dis	34.96 + 4.37	i 56.46 + 7.58***	i 17()+)2 ±
0.0001%		:	I g 42****

EXAMPLES 5 TO 9- HAIR TREATMENT COMPOSITIONS

In a preferred embodiment, the composition is formulated for topical application as defined herein. In one embodiment the composition is an emulsion or cream or a rub.

In an embodiment the cream comprises an excipient or diluent, a suspending agent, a preservative and an effective amount of chondroitin disaccharide and L-fucose.

In an embodiment the cream comprises an alcohol, a carbomer, a sorbate, water, and an effective amount of chondroitin sulphate and L-fucose.

Preferably the alcohol is butylene glycol (1,3-butanediol). The alcohol may be present in an amount of between 1 and 10 % of the composition, preferably between 2 and 6%, preferably 4%. The sorbate may be polysorbate-20. The sorbate may be present in an amount of between .01 to 1% of the composition, preferably between .05 and .5%, preferably 0.10%. Water is present in an amount of between 10% and 90%, preferably 30% to 75%. The carbomer may be present in an amount of from 0.05% to 1%, preferably, 0.1% to 0.5%, preferably, 0.15%. The carbomer may be Ultrez 10.

The actives may be included in an amount of 1.0 to 0.005 % L-fucose (w/v) and 0.1 to 0.00001 % chondroitin di saccharide (w/v).

The composition may further comprise one or more of sugar alcohol such as glycerine, parabens, silicon, such as cyclohexasiloxane, a fatty alcohol or phosphoric acid or a mixture of fatty alcohol and phosphoric acid, such as cetearyl alcohol, dicetyl phosphate and Cereth 10 phosphate or combinations thereof, a polyoxyethylene stearyl ethers, such as Steareth 2 and 10, and a fragrance.

An exemplary rub or emulsion is follows in Example 5.

Ingredient	Exemplary (w/w)%
Phase A Water	70.95
Carbomer	0.15
Phase B Glycerin	3.5
Phase C Steareth 2	0.40
Cetearyl alcohol dicetyl phosphate and Ceteth 10	4
phosphate Cyclohexsiloxane	2
Dioctyl succinate	7
Steareth 10	1.2
Mixed parabens	0.30
Phase D Sorbate	0.10
Phase E Water	2.50
Sodium hydroxide	0.30
Phase F Fragrance	0.10
Phase G chondroitin disaccharide Δ di-4S sodium salt	0.001
L-fucose	0.1

The resulting emulsion is suited as a rub. In addition, the rub is suitable for fragile aged skin.

The emulsion is suitable for improving hair growth and condition, and inhibiting hair loss.

Percentages are examples only and it will be appreciated that any suitable percentage may be used depending on the use.

The emulsion is prepared in the following way: Phase A: disperse Ultrez 10 (carbomer) in water and let is swell for 20 minutes, then add phase B; heat to 75°C. Heat Phase C separately to 75°C. Mix the two phases under stirring, homogenise, add Phase D, neutralise with Phase E, cool until reaching 30°C, then add Phase F and Phase G; adjust to pH to 6 with -NaOH. It 15 will be understood that this is an example only and any suitable method known in the art may be used.

In a further embodiment, the composition may comprise one or more of water, a carbomer, a sorbate such as potassium sorbate, a sugar alcohol, such as glycerine, an alcohol such as 2(2-Ethoxyethoxy)ethanol, a polyoxyethylene stearyl ethers, such as Steareth 2, a fatty alcohol or phosphoric acid or a mixture of fatty alcohol and phosphoric acid , such as cetearyl alcohol, dicetyl phosphate and Cereth 10 phosphate or combinations thereof, a siloxane, such as cyclomethicone, a Caprylic Capric Triglycerides, a sorbitan Stearate, Parabens, Sodium hydroxide, chondroitin disaccharide and L-fucose.

The following composition in Example 6 is an example of an emulsion or cream or a rub.

Ingredient	Exemplary (w/w)%
Water Deionised	qs 100
Carbomer	0.10
Potassium Sorbate	0.10
Transcutol	3.00
Glycerin	8.00
Volpo S2 [Steareth 2]	0.60
Crodafos CES [Cetearyl Alcohol (and) Dicetyl Phosphate	4.00
(and) Ceteth 10 Phosphate]
DC 344 [Cyclomethicone]	2.00
Crodamol GTCC [Caprylic/Capric triglyceride]	10.00
Crill 3 [Sorbitan Stearate]	1.60
	0.30
Mixed Parabens
	0.35
Sodium Hydroxide 30%	3.50
Water Deionised
	3.00
chondroitin disaccharide Δ di-4S sodium salt	0.0001
L-fucose	0.01

This formulation can be made according to the procedures generally outlined in Example 1.

The composition may be an emulsion or cream or rub comprising one or more of water, a carbomer, such as Ultrez 10, a sugar alcohol, such as glycerine, an alcohol such as phenova (phenoxyethanol and mixed parabens), a fatty acid ester such as ethylhexyl palmitate, a fatty alcohol such as cetearyl alcohol, a lactic acid ester such as myristyl lactate, a sorbate such as polysorbate 20 and/or potassium sorbate, a polymeric emulsifier such as Acrylate (C10-30 alkyl acrylate) and a cross polymer, a siloxane, such as cyclomethicone, sodium hydroxide, and the active agents

The following composition in Example 7 is an example of an emulsion or cream. In an embodiment, the emulsion or cream is an anti-stretch mark cream.

Ingredient	Exemplary (w/w)%
Part A
Water Deionised	qs 100
Ultrez 10 [Carbomer]	0.40
Part B
Glycerin	5.00
Phenova | Phenoxyethanol (and) Mixed Parabens]	0.80
Part C
Crodamol OP [Ethylhexyl Palmitate]	4.00
Crodacol CS90 [Cetearyl alcohol]	0.50
Crodamol ML [Myristyl Lactate]	0.30
	1.00
Crillet 1 [Polysorbate 20]
Part D	0.20
PemulenTR2 [Acrylates/C 10-30 Alkyl
Acrylate (and) Crosspolymer]
	2.00
DC 345 [Cyclomethicone]
Part E	0.10
Potassium Sorbate
Part F	6.00
Water	0.60
Sodium Hydroxide 38%
Part G	0.005
chondroitin disaccharide Δ di-4S sodium salt	0.5
L-fucose

This emulsion or rub is prepared in the following way: Phase A disperse Ultrez 10 (carbomer) in water and let it swell for 20 minutes, then add phase B; heat to 75°C. Heat Phase C separately to 75°C. Mix the two phases under stirring, homogenise, add Phase D, neutralise with Phase E, cool until reaching 30°C., then add Phase F and Phase G, adjust pH to -6 with 10 NaOH.

In an embodiment of the invention the composition may be an emulsion, cream or a gel, preferably a gel, comprising one or more of water, a carbomer, such as Ultrez 10, a sugar alcohol, such as glycerine, an alcohol such as phenova (phenoxyethanol and mixed parabens), 15 a sorbate such as polysorbate 20 and/or potassium sorbate, a polymeric emulsifier such as

Acrylate (Cio-so alkyl acrylate), a siloxane, such as cyclomethicone, sodium hydroxide, an active agent and optionally a suitable moisturising agent, such as an agent comprising Imperata cylindrica (root) extract, water, glycerine, PEG-8, and carbomer (MOIST 24). In an embodiment, the gel is a moisturising gel.

The following composition in Example 8 is an example of a gel. In an embodiment, the gel is a moisturising gel.

Ingredient	Exemplary (w/w)%
Part A
Ultrez 10 [Carbomer]	0.20
Water Deionised	qs 100
Part B
Glycerin	3.00
Phenova | Phenoxyethanol (and) Mixed Parabens]	0.80
Part C
Crillet 1 [Polysorbate 20]	0.50
Part D
Potassium Sorbate	0.10
Part E
PemulenTRl [Aciylates/C10-30 Alkyl	0.20
Acrylate Crosspolymer]	3.00
DC 345 [Cyclomethicone]	2.00
Part F
Water	4.00
Sodium Hydroxide 38%	0.40
Part G
chondroitin disaccharide Δ di-4S sodium salt	0.0001
L-fucose	0.1

This formulation can be made according to the procedures generally outlined in Example 3.

Equivalents

The foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.

Claims (15)

CLAIMS:

1. A composition comprising effective amounts of L-fucose and chondroitin disaccharide, formulated for topical application to the hair, or skin where hair is growing, or formulated for oral administration.

2. A composition according to Claim 1 formulated for topical application to the hair, or skin where hair is growing.

3. A composition according to Claim 1 or 2, including 1.0 to 0.005 % L-fucose (w/v) and 0.1 to 0.00001 % chondroitin disaccharide (w/v).

4. A composition according to any preceding Claim, including 0.5 to 0.005 % L-fucose (w/v).

5. A composition according to any preceding Claim, including 0.1 to 0.01 % L-fucose (w/v) and

6. A composition according to any preceding Claim, including 0.05 to 0.00005 % chondroitin disaccharide (w/v).

7. A composition according to Claim 5, including 0.01 to 0.0001 % chondroitin disaccharide (w/v).

8. A composition according to Claim 1, including 0.5 to 0.005 % L-fucose (w/v) and 0.05 to 0.00005 % chondroitin disaccharide (w/v).

9. A composition according to Claim 1, including 0.1 to 0.01 % L-fucose (w/v) and 0.01 to 0.0001 % chondroitin disaccharide (w/v).

10. A composition according to any of Claims 2 to 8, selected from a gel, cream, ointment or lotion.

11. A composition according to any preceding Claim, including one or more cosmetically acceptable excipients.

12. A non-therapeutic method of treating a mammal to improve the growth or condition, or inhibit loss, of the mammals’ hair, the method comprising a step of oral or topical administration of an effective amount of the composition of any of Claims 1 to 10 to the mammal.

13. A non-therapeutic method according to Claim 12, in which the composition is formulated for topical application to the hair, or skin where hair is growing, of the mammal, and in which the composition is topically applied to the hair or skin here hair is growing of the mammal.

14. A composition according to any of Claims 1 to 11, for use in a method of inhibiting hair loss or promoting hair growth in a subject with a condition characterised by excessive hair loss of impaired hair growth, in which the composition is formulated for topical application to the hair, or skin where hair is growing, of the mammal, wherein the composition is topically applied to the hair or

10 skin here hair is growing of the mammal, or in which the composition is formulated for oral administration the mammal, wherein the composition is orally administered the mammal.

15. A composition according to any of Claims 1 to 11, for use of Claim 14, in which the composition is formulated for topical application to the hair, or skin where hair is growing, of the

15 mammal, and in which the composition is topically applied to the hair, or skin where hair is growing, of the mammal.