WO 2011/130787 PCT/AU2011/000451 1 Method for improving the health of skin Field of the Invention The present invention relates to a method for improving the health of the skin of a subject by s administration of an oral composition. Background of the Invention Many people seek to improve the visual appearance of their skin. As a result, a great deal of research has focused on developing products which are capable of- improving the characteristics of io skin which are responsible for its appearance. It is believed that skin appearance is influenced to an extent by the health and condition of the lower layers of the dermis and the dermoepidermal junction (DEJ). -However, most commercially available skin care products are adapted for topical application, meaning that at best the active ingredients therein penetrate only several layers of skin and are ultimately unable to reach or penetrate the lower layers of the dermis or the DEJ. There is is therefore a need for methods in which the health and condition of the lower layers of the dermis and the DEJ can be optimised so as to improve the visual appearance of the skin. Summary of the Invention In a first aspect, the present Invention provides a method for improving the health of the skin of a 20 subject, the method comprising oral administration to the subject of a composition comprising resveratrol, a proanthocyanldin, grape skin extract and vitamin C. - The grape skin extract may be obtained from Vitis vinifera. 25 The amount of grape skin extract present in the composition may be between about 10 mg and about 200 mg. In one embodiment the amount of grape skin extract present in the composition is about 30 mg. The amount of resveratrol present in the- composition may be between about 25 mg and about 30 300 mg. In one embodiment the amount of resveratrol present in the composition is about. 100 mg. The resveratrol may be present in the composition as an extract. The extract may be obtained from WO 2011/130787 PCT/AU2011/000451 2 Polygonum cuspidatum or Polygonum sachalinense. The amount of the proanthocyanidin present in the composition may be between about 15 mg and about 80 mg. In one embodiment the amount of the prOanthocyanidin present in the composition is 5 about 47.5 mg. The proanthocyanidin may be present in the composition as an extract. The extract may be obtained from grape seed. The grape may be Vitis vinifera, io The amount of vitamin C present in the composition may be between about 25 mg and about 200 mg. In one embodiment the amount of vitamin C present in the composition is about 50 mg. The composition may further comprise quercetin. The amount of quercetin present in the composition may be between about 10 mg and about 100 mg. In one embodiment the amount of 15 quercetin present in the composition is about 40 mg. The compositions may be synergistic. The composition may further compose one or more pharmaceutically acceptable excipients, 20 diluents or adjuvants. The composition may be in the form of a unit dosage form, for example tablets, capsules or caplets. The method may involve administration of between 1 and 5 dosage forms per day. 25 The composition may be in the form of a food stuff or beverage. In a second aspect, the present invention provides a method for improving the health of the skin of a subject, the method comprising oral administration to the subject of a composition -in unit dosage 30 form comprising about 95 mg to about 105 mg resveratrol, about 45 mg to about 50 mg of a proanthocyanidin, about 28 mg to about 32 mg of a grape skin extract, and about 38-mg to about 40 mg of vitamin C to a subject.
WO 2011/130787 PCT/AU2011/000451 . . 3 In one embodiment the composition comprises about 100 mg of resveratrol, about 47.5 mg of a proanthocyanidin, about 30 mg of grape skin extract and about 50 mg of vitamin C. The composition may further comprise about 40 mg quercetin. Definitions Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and. variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of-elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. 10 In the context of this specification, the terms "a" and "an" are used herein to refer to one or to mor than one (i.e. to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element. is In the context of this specification, the term "proanthocyanidin" refers to flavanol compounds, and in particular oligomers comprising at least one flavanol moiety. Examples of proanthocyanidins include catechins, such as epigallocatechin 3-gallate (EGCG)' In the context of this specification, the term "extract" refers to an active preparation derived from 20 one or more plants. In the context of this specification "active" means that the extract is capable of producing a-desired therapeutic or cosmetic benefit as disclosed herein. An extract is obtained by a process of "extraction" which will be understood by those skilled in the art as, in general terms,. treatment of plant material (for example, fruit, fruit skin, leaves, seed, bark, roots, stems and the like)-with a solvent, a liquid, or a supercritical fluid to dissolve the active compound(s) and separate 25 the same from residual unwanted plant material. An extract may be in liquid form (for example as a decoction, solution, infusion or tincture) or solid form (for example as a powder or granules). In the context of this specification, the term "pharmaceutically acceptable" means that 'the. compound to which it refers is suitable for use in contact with tissues of the body without undue 30 toxicity, incoipatibiilty, instability, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio.
WO 2011/130787 PCT/AU2011/000451 4 in the context of this specification, the terms "improve" and "improving" refer to the ability to achieve a measurable benefit in relation to the health of skin (such as the appearance and/or texture of the skin), or otherwise prevent, hinder, retard, or reverse the deterioration in the appearance of the skin in any way whatsoever. Thus the terms "improve", "improving" and the like are to be considered in -5 their broadest context. In the context of this specification, "food", "foods", "beverage" or "beverages" includes but is not limited to health foods, functional foods and foods for specified health use. When such food or beverage of the present invention is used for subjects other than humans, the term can be used to io include a feedstuff. In the context of this specification, the term "about," is understood to refer to a range of numbers that a person of skill in the art would consider equivalent to the recited value in the context of achieving the same function or result. In the context of this specification, the term "subject" includes humans, primates, livestock animals (eg. sheep, pigs, cattle, horses, donkeys), laboratory test animals (eg. mice, rabbits, rats, guinea pigs), companion animals (eg. dogs, cats) and captive wild animals (eg. foxes, kangaroos, deer). Typically, the subject is a human or a laboratory test animal. Even more typically, the subject is a 20 human. Detailed Description of the Invention The present inventors have surprisingly discovered that it is possible to improve the health of the skin of a subject by the oral administration to the subject of a composition comprising resveratrol, a 25 proanthocyanidin, grape.skin extract and vitamin C. The compositions of the present invention provide an optimal combination of nutritional ingredients which, when administered orally, nourish the lower layers of the dermis and the DEJ. The compositions of the present invention may improve the health of the skin of a subject by 30 providing cosmetic improvements including: - anti-ageing effects - reduction in wrinkles or visible lines - improved skin texture protection against oxidative stress WO 2011/130787 PCT/AU2011/000451 5 - promotion of collagen production - skin lightening effects - promotion of skin repair - improvement in collagen cross-linking s - supporting the skin barrier function - increasing skin radiance In accordance with particular embodiments of the invention the amount of resveratrol present in the composition may be between about 25 mg and about 300 mg, or more typically between about 1o 25 mg and about 200 mg, or between about 50 mg and abouf 150 mg. Alternatively, the composition may comprise about 55:mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, or 145 mg of resveratrol. 1s The resveratrol may be present in the composition in a highly pure form (for example greater than 98% pure), or altemaively as part of an extract. The extract may be obtained from Polygonum cuspidatum or Polygonum sachalinense, or indeed any other plant or part thereof which contains resveratrol (for example cranberries, blueberries, mulberries, raspberries and certain pine trees). The resveratrol may be present in the composition in the form of a salt or derivative thereof. 20 Suitable derivatives include compounds wherein one or more of the hydroxy groups are derivatised, for example acylated or alkylated.. In accordance with particular embodiments of the invention the amount of proanthocyanidin present in the composition may be between about 15 mg and about 80 mg, or between about 25 mg and 2s about 60 mg, or between about 35 mg and about 55 mg. Alternatively, the composition may comprise about 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, or 54 mg of a proanthocyanidin. 30 The proanthocyanidin may be present in the composition in a highly pure form (for example greater than 98% pure), or alternatively as part of an extract. The proanthocyanidin may be obtained.from grape seed, for example grape seed of Vitis. vinifera. Those skilled in the art will appreciate that the proanthocyanidin may also be extracted from many other plants or parts thereof, for example, apples, pine bark, cinnamon, cocoa, grape skin, bilberries, cranberries, chokeberries, WO 2011/130787 PCT/AU2011/000451 6 blackcurrants, green tea, black 'tea, Quercus petraea and Quercus robur heartwood. The proanthocyanidin may be present in the composition in .the form of a salt or derivative thereof. Suitable derivatives include compounds wherein one or more of the hydroxy groups are derivatised, for example acylated or alkylated. .5 In accordance with particular embodiments of the invention the amount of grape skin-extract present in the composition may be between about 10 mg. and about 200 mg, or between about 10 mg and about 100 mg, or between about 20 mg and about 50 mg. Altematively, the composition may comprise about 25 mg, 30 mg, 35 mg, 40 mg, or 45 mg of grape skin extract. 10 The grape skin extract may be obtained from any species of the Vitis genus. The species may be Vitis vinifera. Those skilled in the art will appreciate that the grape skin extract maj also be obtained.from other species of the Vitis genus, including but not limited to Vitis mustangensis, Vitis aestivalis, Vis ripaa, Vitis rotundfolia, and Vitis labrusca. . 15* In accordance with particular embodiments of the invention the amount.of vitamin C present in the composition may be between about 25 mg and about 200 mg, or between about 25 mg and about 100 mg, or between about 35 mg and about 65 mg. Alternatively, the composition may comprise about 40 mg, 45 mg, 50 mg,55 mg, or 60 mg vitamin C. 20 The compositions of the invention are administered orally and may be conveniently presented in 'unit dosage form and prepared by any of the methods well known in the art of pharmacy. The method may include the step of bringing the components of the composition into association with a carrier which constitutes one or more accessory ingredients. In general, the compositions are 25 prepared by uniformly and intimately bringing into association the components of the composition with a liquid carrier or finely divided solid carrier, or both and then, if necessary, shaping the product into the desired composition. Compositions suitable for oral administration may be presented as discrete units (i.e. dosage 30 forms) such as gelatine or HPMC capsules, cachets or tablets, each containing a predetermined amount of each component of the composition as a powder, granules, as a solution or a suspension in an aqueous liquid or a non-aqueous liquid, or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsiQn.
WO 2011/130787 PCT/AU2011/000451 7 When the composition is formulated as capsules, the components of the composition may be formulated with one or more pharmaceutically acceptable carriers such as starch, lactose, microcrystalline cellulose and/or silicon dioxide. Additional ingredients may include lubricants such as magnesium stearate and/or calcium stearate. 5 Tablets may be prepared by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the components of the composition in a free-flowing. form such as a powder or granules, optionally mixed with a binder, lubricant (for example magnesium stearate or calcium stearate), inert diluent io or a surface active/dispersing agent. Moulded tablets may be made by moulding a mixture of the powdered composition moistened with an inert liquid diluent, in a, suitable machine. The tablets may optionally be. coated, for example, with an enteric coating and may be formulated so as to provide slow or controlled release of the composition therein. 15 Between 1 and 5 unit dosage forms may be administered per day. However, the skilled addressee will also appreciate that the specific dosing regimen (with respect for. example to frequency and duration of administration) to be employed in accordance with embodiments of the invention may be determined.on a. case-by-case basis. Such determinations 're well within the capabilities of those skilled in the art without undue burden or experimentation. 20 Further, it will be understood. that the specific dose level of a composition of the invention for any particular individual will depend upon a variety of factors including, for example, the activity of the resveratrol, proanthocyanidin, grape skin and vitamin C employed, the age, body weight, general health and diet of the individual to be treated, the time of administration, rate of excretion, and -25 combination with any other treatment or therapy. Single or multiple daily administrations can be . carried out with dose levels. A broad range of doses may be applicable. The present invention contemplates combination therapies, wherein compositions as disclosed herein are coadministered with other suitable treatments which may facilitate the desired cosmetic 30 effect. For example, one may seek to aid the improvement of the appearance of the skin using additional selected oral supplements or selected topical compositions in combination by coadministration or sequential administration with the compositions disclosed herein. By Ucoadministered" is meant simultaneous administration in the same formulation or in two different formulations via the same or different routes or sequential administration by the same or different WO 2011/130787 PCT/AU2011/000451 8. routes. By "sequential" administration is meant a time difference of from seconds, minutes, hours or days between the administration of the two types of composition. The compositions may be administered in any order. 5 The present invention contemplates the administration of the composition in a food or beverage. The food may be a solid form or a liquid form. Specific examples of the types of foods or beverages include, but are not limited to soft drinks, carbonated drinks, nutritional beverages, fruit beverages, and milk beverages (including a concentrated stock solution of such a beverage and a dry powder for preparation of such a beverage); confectionery such as chewing gum and chocolate; io dairy products such as milk, yogurt, butter, and cheese. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known. is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms 15 part of the common general knowledge in the field of endeavour to which this specification relates. The present invention will now be described with reference to the following specific examples, which should :not be construed as in any way limiting the scope of the invention. 20 Examples Example I -Oral composition By. way of example only a suitable oral composition for use in accordance with the invention is outlined below. The following is to be construed as merely an illustrative example of a composition 25 and not as a limitation of the scope of the present invention in any way. A typical composition fdr oral administration is outlined below: Each capsule or tablet comprises: Herbal extracts equiv. to dry: 30 Polygonum cuspidatum (giant knotweed) root 20-g equiv. resveratrol 100 mg Vitis vinifera (grape) seed 6 g equiv. proanthecyanidins 47.5 mg Vitis vinifera (grape) skin 30 mg WO 2011/130787 PCT/AU2011/000451 9 Nutrients: Ascorbic acid (vitamin C) 50 mg Quercetin 40 mg Dosage: 1 capsule or tablet once to three times daily.