Composition for skin health

Abstract

The present invention relates to a composition for improving skin health and / or appearance. The composition comprises digestible keratin, collagen and kiwifruit material, and it can be formulated for oral consumption or topical application.

Description

[0001] COMPOSITION FOR SKIN HEALTH

[0002] 1. FIELD OF THE INVENTION

[0003] The present invention relates to a composition for improving skin health and / or appearance. The composition comprises digestible keratin, collagen and kiwifruit material, and it can be formulated for oral consumption or topical application.

[0004] 2. BACKGROUND TO THE INVENTION

[0005] Modern society places great emphasis on appearance, with many people wishing to present a relatively youthful facial appearance. Unfortunately, people are increasingly exposed to stress, including work stress, environmental stress caused by UV light and atmospheric pollution, and dietary stress caused by processed foods. These stresses have a detrimental effect on the skin and can cause a reduction in youthful facial appearance, sometimes termed "premature aging". Accordingly, there is significant societal demand for the reversal of the effects of the above stresses on skin appearance.

[0006] Despite a wide range of dietary supplements and topical formulations used to try and reverse these effects, the degradation of skin health and skin cells remains an unsolved problem. It is an object of this invention to provide a composition that helps to reduce or reverse the effects of these stresses thereby providing a means of going at least partway towards solving this problem, and / or that at least provides the public with a useful choice.

[0007] In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.

[0008] 3. SUMMARY OF THE INVENTION

[0009] The invention relates to a composition comprising:

[0010] (a) collagen,

[0011] (b) digestible keratin, and

[0012] (c) kiwifruit material.

[0013] In one embodiment the collagen comprises hydrolysed collagen. In one embodiment the hydrolysed collagen is ovine collagen. In one embodiment the collagen is at least about 80 wt%, 85 wt% or 90 wt% protein, preferably at least about 85 wt% protein. In one embodiment the digestible keratin is at least about 70, 75, 80, 85, 90 or 95% digestible. In one embodiment the digestible keratin comprises at least about 65, 70 or 75 wt% protein, preferably at least about 70 wt% protein. In one embodiment the digestible keratin is ovine keratin.

[0014] In one embodiment the kiwifruit material is the skin of Actinidia deliciosa or Actinidia chinensis, preferably Actinidia deliciosa. In one embodiment the kiwifruit material comprises at least about 20 mg phenolics per g kiwifruit material, preferably at least about 25 mg phenolics per g kiwifruit material. In one embodiment the kiwifruit material comprises at least about 200 mg soluble fibre per g kiwifruit material, preferably at least about 250 mg soluble fibre per g kiwifruit material.

[0015] In one embodiment the composition comprises or consists essentially of:

[0016] (a) ovine collagen,

[0017] (b) digestible ovine keratin, and

[0018] (c) kiwifruit skin, in a dry weight ratio of 6.25: 1: 1.25.

[0019] In one aspect the invention provides a nutritional supplement comprising a composition of the invention and one or more nutraceutically acceptable excipients, carriers and / or diluents. In one embodiment the nutritional supplement is in the form of a soluble powder, concentrated liquid formulation, liquid beverage, supplement bar, dietary supplement capsule or gummy sweets.

[0020] In one aspect the invention provides a topical formulation comprising a composition of the invention and one or more cosmetically acceptable excipients, carriers and / or diluents.

[0021] In one aspect the invention provides a method of increasing keratinocyte viability in a subject comprising administration of a composition, supplement or formulation of the invention to the subject.

[0022] 4. DETAILED DESCRIPTION OF THE INVENTION

[0023] 4.1 Definitions and abbreviations

[0024] As used herein the term "comprising" means "consisting at least in part of". When interpreting each statement in this specification that includes the term "comprising", features other than that or those prefaced by the term may also be present. Related terms such as "comprise" and "comprises" are to be interpreted in the same manner.

[0025] The term "about" as used herein means a reasonable amount of deviation of the modified term such that the end result is not significantly changed. For example, when applied to a value, the term should be construed as including a deviation of+ / - 5% of the value.

[0026] It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7) and, therefore, all sub-ranges of all ranges expressly disclosed herein are hereby expressly disclosed. These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner.

[0027] Whenever a range is given in the specification, for example, a temperature range, a time range, or a composition range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the disclosure. In the disclosure and the claims, "and / or" means additionally or alternatively. Moreover, any use of a term in the singular also encompasses plural forms.

[0028] 4.1 The composition of the invention

[0029] Keratinocytes occur on the outermost layer of the skin. As a result, an increase in keratinocyte cell viability is directly associated with improvements in skin health, by building the skin barrier function, the dermal-epidermal junction associated with wrinkle formation, and by increasing skin firmness through collagen synthesis.

[0030] The composition of the invention comprises three essential components - collagen, digestible keratin and kiwifruit material. This composition provides a surprising stimulating effect on skin cells and specifically improves the viability of human keratinocytes. The stimulating effect on skin is greater than observed for the components alone or in any other combination, indicating the presence of a synergistic mechanism (see Example 1).

[0031] Based on the results provided in the present disclosure, the inventors believe that oral consumption or topical application of the composition of the invention is reasonably expected to lead to associated benefits in skin health and cosmetic appearance.

[0032] Collagen is the most abundant protein in mammals, found usually in connective tissue including cartilage, bones, tendons, ligaments and skin. Collagen derived from mammalian or marine sources such as bovine, ovine, cervine, caprine or piscine skin is a protein frequently used in dietary supplements and functional foods. Such supplements and / or foods are commonly consumed for enhancing beauty or providing benefits associated with joint health and mobility. Many different types of collagen are known, each type being characterized by different three-dimensional structure.

[0033] Collagen I, II or III are typically most prevalent in the skin and are responsible for the volume and structure of the skin and other soft tissues. Collagen IV is a junctional protein known to act in the basement membrane, for example where the dermis and epidermis are joined. Collagen IV is rarely provided in dietary supplements, but it is a protein of significant importance to the health of tissue.

[0034] While types I and III collagen are preferred, all types of collagen are suitable for use in the composition of the invention.

[0035] In one embodiment the composition of the invention comprises bovine, ovine, cervine, piscine, caprine or equine collagen, or combinations thereof. In one embodiment, the collagen is ovine collagen. Collagen can be extracted from its biological source by a range of methods, including as described in NZ 536193, incorporated by reference herein in its entirety.

[0036] Collagen comprised in the composition of the invention, may be in any form including intact or hydrolysed collagen. Intact collagen is a complex protein comprising three amino acid chains. While collagen is not soluble, it is readily digestible. Hydrolysed collagen comprises a group of peptides of low molecular weight. Hydrolysed collagen is obtained by enzymatic action and is often produced by enzymatic digestion of agro-food waste such as bones, tendons and skin.

[0037] In one embodiment the composition of the invention comprises hydrolysed or intact collagen, preferably hydrolysed collagen.

[0038] The purity of collagen can vary, as indicated by its protein content. Collagen for use in the composition of the invention must be high in protein. In one embodiment, the collagen is at least about 80, 85 or 90 wt% protein. Preferably, the collagen is at least about 85 wt% protein.

[0039] In one embodiment the collagen is hydrolysed type I and / or hydrolysed type II ovine collagen of at least 85 wt% protein.

[0040] Keratin is a scleroprotein found in wool, hair, horns, hooves, feathers and the outer layer of the skin of animals. Keratin is typically a tough and insoluble protein known to be indigestible due to the high proportion of the amino acid cystine compared to other proteins. Multiple cystine residues form crosslinks that make keratin enzyme resistant, resulting in a protein that is generally of low nutritional value. Keratin can be extracted from a keratin source using a variety of techniques including chemical (such as oxidation, reduction, hydrolysis and sulfitolysis), enzymatic / microbial, dissolution in ionic liquids, microwave irradiation, steam explosion and thermal hydrolysis.

[0041] Chemical extraction processes generally break the disulfide crosslinks within and between keratin proteins, increasing both solubility and digestibility. For example, US 7,148,327, incorporated by reference herein in its entirety, describes such a process.

[0042] In this digestible form keratin has been used in dietary supplements to confer benefits associated with beauty and joint health. Digestible keratin, comprised in the composition of the invention, is keratin that has been modified to render it digestible. The term "digestible keratin" as used herein, means keratin that has an in vitro digestibility of at least 70% using the standard pepsin digestibility assay according to the procedure of the Association of Official Analytical Chemists (Official Methods of Analysis (13th Rev. ed), Association of Official Analytical Chemists, Washington, D.C (1980)).

[0043] Keratin may be modified for digestibility using any method known in the art. In addition to chemical processes that breaking the cystine crosslinks, protein hydrolysis may also be used to increase digestibility. Modification for digestibility typically takes place as part of the keratin isolation process.

[0044] The term "digestible keratin" includes keratin derivatives such as S-sulfonated keratin, oxidised keratin and keratin peptides, all of which may be produced during the digestibility process.

[0045] In one embodiment the digestible keratin is at least about 70, 75, 80, 85, 90 or 95% digestible.

[0046] The digestibility of keratin can be increased by methods that also convert much of the cystine present to the amino acid cysteic acid, such as by a method disclosed in US application 13 / 381,766 (published as US 2012 / 0219667), incorporated by reference herein in its entirety. This method involves heating the keratin source in an oxidising solution at acidic pH to oxidise the cystine components to cysteic acid, further heating at neutral pH, removing residual oxidisers and salts and then drying and milling the digestible keratin powder. Keratin that is rich in cysteic acid is thought to have increased nutritional value.

[0047] In one embodiment the digestible keratin is isolated from ovine wool. In one embodiment, the keratin has been isolated from ovine wool using the method outlined in US 2012 / 0219667. In one embodiment the keratin was extracted from a keratin source using the following method:

[0048] (a) adding an insoluble keratin source to an aqueous solution of oxidizing agent at 90° C and holding the mixture at 90° C. for 90 minutes,

[0049] (b) cooling the mixture to 60° C then adding an amount of base sufficient to raise the pH to produce the protein salt, but keeping the pH below 7.5,

[0050] (c) heating back up to 90° C and holding for about 40 minutes while maintaining the pH below 6.1.

[0051] In one embodiment the digestible keratin comprises at least about 65, 70 or 75 wt% protein, preferably at least about 70 wt% protein.

[0052] Kiwifruit is the edible berry of several species of woody vine plants in the genus Actinidia. The most common kiwifruit cultivar (Actinidia deliciosa "Haywood") is oval, about 5-8 cm long with a thin, fuzzy light brown skin. The fruit is light green or golden with a soft texture and sweet flavour. Another popular cultivar is Actinidia chinensis "Gold", which has yellow flesh. The term "kiwifruit material" as used herein, means the flesh, skin and / or seeds of a berry of any kiwifruit Actinidia) species or an extract thereof.

[0053] In one embodiment, the kiwifruit material is from A ctinidia deliciosa or Actinidia chinensis, preferably Actinidia deliciosa.

[0054] In one embodiment the composition of the invention comprises an extract of kiwifruit skin. Kiwifruit skin extracts may be obtained by water extraction of macerated kiwifruit skin, followed by freeze-drying.

[0055] In one embodiment the kiwifruit skin extract comprises at least about 20 mg phenolics per g extract, preferably at least about 25 mg phenolics per g extract.

[0056] In one embodiment the kiwifruit skin extract comprises at least about 200 mg soluble fibre per g extract, preferably at least about 250 mg soluble fibre per g extract.

[0057] In one embodiment the invention relates to a composition comprising or consisting essentially of:

[0058] (a) collagen,

[0059] (b) digestible keratin, and

[0060] (c) kiwifruit material.

[0061] The inventors have surprisingly found that compositions of the invention comprising the three components within a particular range of weight ratios are the most effective at increasing the viability of human keratinocytes. In one embodiment the dry weight ratio of components (a):(b):(c) is about 4 to 8: 0.5 to 2:0.5 to 2.

[0062] In one embodiment the dry weight ratio of components (a):(b):(c) is about 4 to 8: 1 :0.5 to 2.

[0063] In one embodiment the dry weight ratio of components (a):(b):(c) is about 6.25:0.5 to 2:0.5 to 2.

[0064] In one embodiment the dry weight ratio of components (a):(b):(c) is about 4 to 8:0.5 to 2: 1.25.

[0065] In one aspect the invention provides a composition comprising:

[0066] (a) ovine collagen,

[0067] (b) digestible ovine keratin, and

[0068] (c) kiwifruit skin, in a dry weight ratio of 6.25: 1: 1.25.

[0069] 4.2 Formulations of the composition of the invention

[0070] The composition of the invention can be directly added to foods or beverages including milks (dairy or plant based), hot beverages, cookies and other baked goods and water. Alternatively, the composition of the invention can be formulated into a nutritional supplement or topical formulation.

[0071] In one aspect the invention provides a nutritional supplement comprising a composition of the invention and one or more nutraceutically acceptable excipients, carriers and / or diluents. Nutraceutically acceptable excipients, carriers and diluents include but are not limited to vitamins such as vitamin C, fillers such as maltodextrin and microcrystalline cellulose, flavourings, preservatives, sweeteners (natural and artificial) and the like.

[0072] In one embodiment the nutritional supplement is a soluble powder. In one embodiment the soluble powder comprises 3.4 g of the composition of the invention with lOOmg vitamin C and 1g maltodextrin.

[0073] In another embodiment the nutritional supplement is a concentrated liquid formulation. A concentrated liquid formulation can be added to another beverage, as a "shot". In one embodiment the concentrated liquid formulation comprises 3.4 g of the composition of the invention suspended in 25 ml water and 0.25 g sodium benzoate preservative.

[0074] In one embodiment the nutritional supplement is a liquid beverage. In one embodiment the liquid beverage comprises 3.4 g of the composition of the invention, 10g sucrose, 1g vitamin C, and small amounts of colouring and flavouring agents in 250ml of water or soda water.

[0075] In one embodiment the nutritional supplement is a supplement bar. In one embodiment the supplement bar comprises 3.4 g of the composition of the invention combined with glucose, milk chocolate, soy lecithin, glycerine, maltodextrin, pineapple juice concentrate, honey, salt and colouring, and has the following properties:

[0076] • Mass 60g

[0077] • Energy 915kJ

[0078] • Protein 20g

[0079] • Total fat 3g

[0080] • Total carbohydrate 27.3g

[0081] In one embodiment the nutritional supplement is formulated as a dietary supplement.

[0082] In one embodiment the dietary supplement is provided as a pill or in a capsule. In one embodiment the nutritional supplement comprises 850mg of the composition of the invention combined with 150 mg microcrystalline cellulose in size 00 capsules for daily administration of 4 capsules per day.

[0083] In one embodiment the nutritional supplement is a gummy. A gummy is a gelatinebased chewable sweet. In one embodiment the gummy comprises 12.5 g of the composition of the invention and 3g of mixed berry flavouring, added to 35g powdered gelatine mixed with 40g water and moulded to produce 1.13g gummies, intended for 3 X daily consumption.

[0084] In one aspect the invention provides a topical formulation comprising a composition of the invention and one or more cosmetically acceptable excipients, carriers and / or diluents. Cosmetically acceptable excipients, carriers and dilulents include, but are not limited to fat and oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbents, preservatives, disinfectants, antioxidants, plant extracts, pH regulators, alcohols, pigments, perfumes, bloodcirculation promoters, refrigerants, antiperspirants and purified water.

[0085] The cosmetic formulations of the invention may be formulated as solutions, emulsions, pastes, creams, gels and the like.

[0086] 4.3 Properties of the compositions of the invention

[0087] The effect of the compositions of the invention on an in vitro cell culture of primary human keratinocytes was investigated by using the MTT cell proliferation assay, as described in Example 1. In this assay the quantity of formazan (directly proportional to the number of viable cells) is measured by recording changes in the absorbance at 570 nm using a plate reading spectrophotometer.

[0088] The composition of the invention (sample 3) showed a 17.2% increase in cell viability over control sample 5, containing the same amount and ratios of keratin and collagen.

[0089] Cell viability is a strong indicator of tissue viability and establishing improved tissue viability on primary human keratinocyte cells more accurately models the potential outcome for full skin than immortalised fibroblasts typically used in cell culture.

[0090] Improved skin cell viability is directly associated with important skin structural properties including moisture content, barrier function, firmness, elasticity, wrinkle structure, depth and volume.

[0091] Accordingly, in one aspect the invention provides a method of increasing keratinocyte viability in a subject comprising administration of a composition, supplement or formulation of the invention to the subject. In one embodiment, the method comprises oral administration of a nutritional supplement of the invention. In another embodiment the method comprises topical administration of a cosmetic formulation of the invention.

[0092] 5. EXAMPLES

[0093] Example 1: Effect of the composition of the invention on viability of primary human keratinocyte cells

[0094] Keratinocytes are one of the major types of cells present in skin. They are the most prominent cell type within the epidermal layer. They provide a barrier against a range of risks including micro-organisms, radiation and heat. They produce a number of pro- inflammatory compounds when skin is exposed to these potential dangers. They also produce a number of the structural constituents of skin such as keratin and filaggrin.

[0095] Primary human keratinocytes (HEKa ATCC No.PCS-200-011) were cultured according to supplier recommendations.

[0096] The collagen used was hydrolysed type I and III ovine collagen. The keratin used in the study was isolated from ovine wool using the method outlined in US 20120219667. The kiwifruit material is a kiwifruit skin aqueous extract. Table 1: Characteristics of the components of the composition of the invention

[0097] N / A means not applicable or not available.

[0098] The amino acid profile of the keratin is shown in Table 2. Table 2: Amino acid profile of keratin used

[0099] The collagen, keratin and kiwifruit powder components were combined by dry mixing. A range of combinations of collagen, keratin and kiwifruit were added to the culture media as detailed in Table 3.

[0100] After culturing the cells at 37°C in 95% Air / 5% CO2 for a total of 24 hours the culture media was aspirated from the plates and the supernatants transferred to 96 well plates. After the removal of the supernatants, 180 pl of fresh medium was added to each well. 20 pl of MTT working solution (5 mg / ml) was be added to each well on the plate and incubated for an additional 4 hours at 37°C. 100 pl of MTT lysis buffer was then be added to each of these wells and the plate incubated for an hour at 37°C. The absorbance of each well was read using a VersaMax microplate reader at 570 nm. Table 3: Mean absorbance at 570 nm of collagen and keratin compositions

[0101] A range of collagen and keratin concentrations were assessed for protein expression and tissue viability. Relative proportions of collagen: keratin of 1: 1, 3: 1 and 6.25: 1 were also assessed. Either alone or in any of the combinations tested, no statistically significant differences were observed for the collagen and keratin combinations. However, on addition of the kiwifruit extract a substantial improved in cell viability was measured. Comparing sample 3 with sample 5 showed a 17.2% increase in cell viability. The protein concentration in each sample was identical (total of 50ug / ml combined with a ratio of collagemkeratin of 6.25: 1) with the only difference being the addition of a low concentration of kiwifruit extract. The relative concentration of collagen: keratin: kiwifruit in the composition was 6.25: 1 : 1.25.

[0102] Example 2: Cosmetic formulations

[0103] Anti-wrinkle formulation An anti-wrinkle cosmetic formulation comprising a composition of the invention was prepared by combining the ingredients set out in Table 4 below. The ingredients are named in accordance with the International Nomenclature Cosmetic Ingredient (INCI) rules. Table 4: Ingredients for formulation

[0104] Moisturising cream

[0105] A moisturising cream comprising a composition of the invention was prepared by combining the ingredients set out in Table 5 below.

[0106] Table 5: Ingredients for formulation

[0107] Intensive serum

[0108] An intensive serum comprising a composition of the invention was prepared by combining the ingredients set out in Table 6 below. Table 6: Ingredients for formulation

[0109] Prophetic example:

[0110] The effectiveness of the 3.4g daily dosage of the collagen, keratin, kiwifruit composition of the invention on skin properties could be determined through a randomised, controlled clinical study with two groups of 35 volunteers. Such a study would entail daily administration of the composition vs a placebo control made from microcrystalline cellulose for 60 days. At periodic time points throughout the study including 0, 30 and 60 days, measurement would be made of the important skin characteristics. Skin moisture content would be measured using a corneometer, skin barrier function would be measured by determination of transepidermal water loss using a TEWA meter, skin firmness and elasticity would be measured using a cutometer and wrinkle characteristics would be measured using high resolution 3D scanning or using silicon imprint technology. Oral consumption of the composition of the invention would be anticipated to lead to improvement in each of these characteristics.

Claims

WHAT WE CLAIM:

1. A composition comprising:(a) collagen,(b) digestible keratin, and(c) kiwifruit material.

2. A composition of claim 1 wherein the collagen comprises hydrolysed collagen.

3. A composition of claim 1 or claim 2 wherein the collagen comprises ovine collagen.

4. A composition of any preceding claim wherein the collagen is at least about 80, 85 or 90 wt% protein, preferably at least about 85 wt% protein.

5. A composition of any preceding claim wherein the digestible keratin was extracted from a keratin source using the following method:(a) adding an insoluble keratin source to an aqueous solution of oxidizing agent at 90° C and holding the mixture at 90° C. for 90 minutes,(b) cooling the mixture to 60° C then adding an amount of base sufficient to raise the pH to produce the protein salt, but keeping the pH below 7.5,(c) heating back up to 90° C and holding for about 40 minutes while maintaining the pH below 6.1.

6. A composition of any preceding claim wherein the digestible keratin is at least about 70, 75, 80, 85, 90 or 95% digestible.

7. A composition of any preceding claim wherein the digestible keratin comprises at least about 65, 70 or 75 wt% protein, preferably at least about 70 wt% protein.

8. A composition of any preceding claim wherein the digestible keratin is ovine keratin.

9. A composition of any preceding claim wherein the kiwifruit material is a skin extract of Actinidia deliciosa or Actinidia chinensis, preferably Actinidia deliciosa.

10. A composition of any preceding claim wherein the kiwifruit material comprises at least about 20 mg phenolics per g kiwifruit material, preferably at least about 25 mg phenolics per g kiwifruit material.

11. A composition of any preceding claim wherein the kiwifruit material comprises at least about 200 mg soluble fibre per g kiwifruit material, preferably at least about 250 mg soluble fibre per g kiwifruit material.

12. A composition of any preceding claim wherein the dry weight ratio of components (a):(b):(c) is about 4 to 8: 0.5 to 2:0.5 to 2 or about 4 to 8: 1:0.5 to 2 or about 6.25:0.5 to 2:0.5 to 2 or about 4 to 8:0.5 to 2: 1.25.

13. A composition of claim 12 wherein the dry weight ratio of components (a):(b):(c) is about 6.25: 1 : 1.25.

14. A nutritional supplement comprising a composition of any one of claims 1 to 13 and one or more nutraceutically acceptable excipients, carriers and / or diluents.

15. A nutritional supplement of claim 14 which is a soluble powder, concentrated liquid formulation, liquid beverage, supplement bar, dietary supplement capsule or gummy sweet.

16. A nutritional supplement of claim 15 which is a soluble powder comprising 3.4 g of the composition of any one of claims 1 to 13, 100 mg vitamin C and 1 g maltodextrin.

17. A nutritional supplement of claim 15 which is a concentrated liquid formulation comprising 3.4 g of the composition of any one of claims 1 to 13 and 0.25 g sodium benzoate preservative suspended in 25 ml water.

18. A nutritional supplement of claim 15 which is a liquid beverage comprising 3.4 g of the composition of any one of claims 1 to 13, 10g sucrose, 1g vitamin C, and small amounts of colouring and flavouring agents in 250ml of water or soda water.

19. A nutritional supplement of claim 15 which is a supplement bar comprising 3.4 g of the composition of any one of claims 1 to 13 combined with glucose, milk chocolate, soy lecithin, glycerine, maltodextrin, pineapple juice concentrate, honey, salt and colouring.

20. A nutritional supplement of claim 19 which has the following properties; mass 60g, energy 915kJ, protein 20g, total fat 3g and total carbohydrate 27.3 g.

21. A nutritional supplement of claim 15 which is a dietary supplement comprising 850mg of the composition of any one of claims 1 to 13 combined with 150 mg microcrystalline cellulose in size 00 capsules for daily administration of 4 capsules per day.

22. A nutritional supplement of claim 15 which is a gummy comprising 12.5 g of the composition of any one of claims 1 to 13 and 3g of mixed berry flavouring, added to 35g powdered gelatine mixed with 40g water and moulded to produce 1.13g gummies, intended for 3 X daily consumption.

23. A topical formulation comprising a composition of any one of claims 1 to 13 and one or more cosmetically acceptable excipients, carriers and / or diluents.

24. A method of increasing keratinocyte viability in a subject comprising administration of a nutritional supplement of any one of claims 14 to 22, or a topical formulation of claim 23 to the subject.

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