WO2000027352A1

WO2000027352A1 - Topical compositions containing whey proteins

Info

Publication number: WO2000027352A1
Application number: PCT/US1999/026650
Authority: WO
Inventors: Donald F. Collins; Thomas Mammone; Kenneth D. Marenus
Original assignee: Color Access, Inc.
Priority date: 1998-11-10
Filing date: 1999-11-10
Publication date: 2000-05-18
Also published as: US6203805B1; EP1047398A1; JP3803030B2; EP1129699A1; AU742131B2; JP2002529387A; CA2317049A1; ZA200003283B; AU1817100A; KR100499294B1; KR20010015900A

Abstract

The present invention relates to topical compositions comprising a collagen enhancing effective amount of a whey protein, vitamin A, vitamin E and vitamin C in combination with each other. Vitamin E and vitamin C components are present in specific ranges based on their inverse effect in boosting collagen synthesis. The compositions can enhance the production of collagen in skin and improve the resiliency of the skin. The increased production of collagen using the compositions of the present invention restores proteins and vitamins to the skin and helps alleviate some of the effects of aging and photoaging of skin. The present invention also includes methods of applying the compositions to the skin.

Description

TOPICAL COMPOSITIONS CONTAINING WHEY PROTEINS

Field of the Invention

The invention relates to topical compositions containing whey protein which significantly increase the synthesis of collagen in skin More specifically, the invention relates to topical compositions containing vitamin C. vitamin E and vitamin A in combination with whey protein which have collagen synthesis enhancing properties

Background of the Invention

Collagen is a fibrous protein that is composed of a triple chain helix structure having a sequence of repeating ammo acids, glycine, and X and Y. X and Y being any ammo acid, but are usually prohne and hydro xyprolme The X and Y ammo acids, particularly proline. in addition to the presence of lmino acid residues, stabilize the helical structure of collagen

Collagen constitutes one quarter of the total amount of protein in the human body It is the major fibrous element of skin, bone tendons, cartilage, ligaments and blood vessels Collagen represents about 70% of skin in terms of its dry weight and helps form the structural network of skin The presence of collagen provides strength and resiliency in skin While there are various types of collagen throughout the body, the collagen in skin is predominantly Type I and Type III, where 80% to 90% is Type I and the remaining 10% to 15% is Type III Other types of collagen in skin, for example. Type IV, V. and I tπmer are present in considerably smaller amounts

Collagen is synthesized by fibroblasts It is believed that as skin ages, the dermis and the epidermis thin because fibroblasts lose their ability to react to growth factors for the proliferation and synthesis of collagen It has also long been recognized that there is a cause-and-effect relationship between prolonged and/or repeated exposure to UV light and the premature aging of skin Excessive exposure to the sun contributes substantially to premature reduction in the quality and quantity of collagen in skin These changes manifest themselves externally by ty pical signs of aging, such as deep lines and wrinkles, loss of elasticity, skin dryness and unevenness. and increased frequency of blotches, pigmented spots, and benign as well as malignant neoplasms Kucharz, E J , "The Collagens Biochemistry and Pathophysiology", (Spπnger-Verlag Berlin Heidelberg 1992), pps 6-29, 79-80, 227-232

To counteract the undesired effects of both types of aging (I e . natural and photo- induced) methods of increasing collagen- sy nthesis have been investigated using, for example, a retinoic acid, aminoethyl compound, certain types of growth factors, ginsenoside, ascorbic acid, or tocopherol. See, for example, Kim et al., The Journal of Investigative Dermatology, 98:359- 363 (1992); Griffiths, C. E. M. et al., The New England Journal of Medicine, 329: 530-535 ( 1993); Chojkier et al., The Journal of Biological Chemistry, 264(28): 16957-16962 ( 1989); U.S. Patent Nos. 5,747,538, 5,747,049 and 5,386,012. In addition, there has been research involving the stimulation of collagen with a peptide. The peptide, in the form of a hydrolysate obtained by fermentation of milk proteins, was found to increase the thickness of the stratum corneum. It did not, however, significantly increase the level of collagen. Augustin et al., Skin Pharmacol 10: 63-70 ( 1997).

Thus, while various species are known to stimulate collagen synthesis, the topical compositions of the present invention provide a synergistic combination that unexpectedly enhances the stimulation of collagen synthesis. As there is a continued desire to maintain the health of the skin for the purpose of appearing attractive and prolonging a youthful look, a boost in the production of collagen in the skin is important and is the object of the present invention.

Summary of the Invention

The present invention relates to cosmetic or pharmaceutical compositions containing whey protein for topical application to the skin and methods of enhancing collagen synthesis in the skin. The components of the composition comprise collagen enhancing effective amounts of (a) a retinoid (hereinafter referred to as vitamin A) and derivatives thereof, (b) an ascorbic acid (hereinafter referred to as vitamin C) and derivatives thereof, (c ) vitamin E and derivatives thereof, and (d) a hey protein. The vitamins E and C components are present in the composition in specific ranges and the vitamin C component is present in an amount less than the vitamin E component to boost collagen synthesis. Therefore, these compositions are useful in the treatment and prevention of the effects of aging and photoaging, i.e.. the damage to the skin which occurs as a result of a decrease in collagen synthesis in skin.

Brief Description of the Drawings

Figure 1 illustrates the percent increase of collagen production (over media control) in response to the presence of 1 ) whey protein ("W P"); 2) vitamin C at a low level of 50 μg/ml ("V-C 50"); 3) vitamin C at a high level of 100 μg/ml ("^*V-C 100"); 4) whey protein with vitamin C at a low level of 50 μg ml (" W P/V-C 50"); 5) whey protein with vitamin C at a high level of 100 μg/ml ('"W P -C 100^'"); 6) hey protein, vitamin A, and vitamin C at a low level of 50 μg/ml ("W P/V-C 50/V-A"), 7) whey protein, vitamin A, and vitamin C at a high level of 100 μg/ml C'W P/V-C 100/V-A"), 8) whey protein, vitamin A, vitamin C at a low level of 50 μg/ml. and vitamin E at a low level of 500 μg/ml ('"W P/V-C 50/V-A/V-E 500"); 9) whey protein, vitamin A, vitamin C at a high level of 100 μg/ml, and vitamin E at a low level of 500 μg/ml ("W P/V-C 100/V-A/V-E 500), 10) whey protein, vitamin A, vitamin C at a low level of 50 μg/ml. and vitamin E at a high level of 1000 μg/ml (W P/V-C 50/V-A/V-E 1000"). and 1 1 ) whey protein, vitamin A, vitamin C at a high level of 100 μg/ml, and vitamin E at a high level of 1000 μg/ml (W P/V-C 100/V-A/V-E 1000)

Detailed Description of the Invention

When vitamins C and E are combined in specific ranges of amounts with the other essential components (i e . the whey protein and vitamin A), it is unexpectedly discovered that there is an inv erse relationship between quantities specific to vitamin C and vitamin E w ith respect to increasing the production of collagen Collagen production is maximized using higher quantities specific to vitamin E and lower quantities specific to vitamin C and conversely, using lower quantities specific to v itamin E and higher quantities specific to vitamin C within certain defined ranges Therefore, to maximize the collagen synthesis enhancing effect of the compositions, the quantities of v itamins C and E are based on this inverse relationship

As noted above it has certainly been recognized that various species are capable of increasing the sy nthesis ot collagen Various types of compounds, including vitamin A, vitamin E, as well as v itamin C. hav e been tested to determine if they may have an ameliorating effect on UV-induced damage Further, while studies in animals have indicated the ability to repair damaged zones in skin due to increased collagen sy nthesis using vitamin A or vitamin C, results of human studies have been inconsistent in showing that the repair zone was actually due to an increase in collagen synthesis See Griffiths et al , supra

It is further known in the prior art to use whey protein for dietary and nutritional purposes as described in U S Patent Nos 5,451 ,412 and 5,456,924 For example, it is known to use a combination of milk protein, ascorbic acid, and vitamin A in a composition used for bathing which cleanses and restores v itamins and proteins to the skin as disclosed in U S Patent No 4,223,018 The use of various compounds alone and/or in combination with each other has increased, however, there is still a lack of understanding of their collective effect on collagen svnthesis in skin The combination of vitamin C, vitamin E and vitamin A with whey protein, when the vitamin C and vitamin E components are present in specific ranges, have now been unexpectedly shown to be capable of boosting the synthesis of collagen greater than about 300 percent, about three times as much as the same amount of whey protein (e.g., 85 percent increase in collagen synthesis, as shown in Figure 1 , using whey protein alone). A first component of the present invention is the whey protein component. Whey protein, or serum lactis, exists in the supernatant of milk and is the portion of milk left over after butterfat, casein and albumin are removed. Since whey proteins are globular, they are, therefore, water soluble and subject to denaturation which increases their ability to hold water. The primary fractions of whey protein are β-lactoglobulins, α-lactalbumins, bovine serum albumin, and immunoglobulins. The group of β-lactoglobuiins accounts for about half of all whey proteins.

In the present invention, the preferred whey protein is denatured and does not contain free a ino acids, caseins, casein-bound calcium and phosphate, fat and fat soluble vitamins. The w hey protein is denatured by the process of treating milk to make cheese as well as other pasteurization processes such as for example, low pH and high temperature pasteurization methods. In a preferred embodiment of the present invention, the whey protein product is offered commercially under the name VersaPRO E from Davisco International, Inc., Le Sueur, Minnesota, or similar products may be obtained from other commercial sources.

The other components of the present invention are known materials that are either commerciall available or readily prepared. These components are used in collagen enhancing effective amounts. By the term "collagen enhancing effective amount" it is meant an amount which, in combination with the other essential components, enhances collagen production by at least 200 percent, preferably by at least 250 percent, most preferably by at least 300 percent. The collagen enhancing effective amount varies depending upon the identity of the components and their potency. The remaining components are essential to fortifying the effect of the compositions of the present invention as collagen synthesis enhancers.

The first additional component is vitamin A and derivatives thereof. By vitamin A or retinoid in the present context is meant vitamin A (retinol) and any natural or synthetic derivatives, homologs or analogs thereof suitable for use on the skin. Example of retinoids, in addition to retinol include, but are not limited to, retinoic acid (vitamin A acid), retinal (vitamin A aldehyde), and retinoic acid esters or amides, e.g., retinyl palmitate or retinyl acetate.

Another additional component is vitamin E or a homolog, analog or derivative thereof. The principle active component of v itamin E is tocopherol. particularly α-tocopherol: however. any vitamin E or tocopherol derivative may be employed. Examples of useful derivatives include but are not limited to, for example, esters such as tocopherol acetate, tocopherol linoleate, tocopherol nicotinate, tocopherol sorbate, or tocopherol succinate; polyethylene glycol ethers of tocopherol, such as tocophereth-5, tocophereth- 10, tocophereth- 12, tocophereth-18 or tocophereth-50 and 6-hydroxychroman homologs, particularly 6-hydroxy-2,5,7,8- tetramethylchroman-2-chroman-2-carboxylic acid, commercially available as Trolox®-C and troloxyl-amino acids. The tocopherol derivative may also be a tocopherol-cysteamine or cosmetically or pharmaceutically acceptable salts thereof. The tocopherol-cysteamine compounds can be made using readily available starting materials. It is within the scope of the present invention to use more than one vitamin E component in the mixture, for example, a mixture ^"containing both α-tocopherol and tocopherol cysteamine.

The third essential additional component is vitamin C or a homolog, analog or derivative thereof. Derivatives of vitamin C which may be used include but are not limited to, for example, ascorbyl esters of fatty acids, such as ascorby palmitate. ascorbyl dipalmitate, ascorbyl dimethylsilanol palmitate, and ascorby stearate, ascorbyl linoleate, ascorbyl acetate; metal or metal phosphate salts, such as magnesium, sodium, or potassium ascorbyl phosphate, or magnesium, sodium or potassium ascorbate.

There is an unexpected increase in collagen synthesis when vitamin E is doubled relative to a standard amount of vitamin E in the presence of the other components (e.g., a combination including 500 μg/ml o ^" v itamin E increases collagen synthesis by about 263% while a combination including 1000 μg ml of vitamin E increases collagen synthesis by about 336%). The increase in collagen synthesis experienced with the present invention is especially surprising because a combination of about 1000 μg/ml of vitamin E, about 100 μg/ml of vitamin C, about 5 μg/ml of vitamin A and about 1 ,000 μg/ml of the whey protein (132% increase) is only merely as effective as about 100 μg/ml of vitamin C alone ( 128% increase) indicating that not all combinations of known collagen enhancers result in a significant additive increase in synthesis. Since increases in vitamin C in combination with other components did not result in an increase in collagen synthesis under the abovementioned circumstances, it is surprising to discover a composition containing a combination of whey protein, vitamin E, vitamin A, and vitamin C having vitamin C and E in specific ranges that enhances the production of collagen as the present invention does. Accordingly, in one embodiment of the present invention, the vitamin E component is present in an amount of less than about 800 μg/ml, more preferably less than about 500 μg/ml and the vitamin C component is present in an amount of from about 20 to about 200 μg/ml, more preferably from about 50 to about 100 μg/ml. The vitamin C component is present, however, in an amount less than the vitamin E component. And, in another embodiment of the present invention, the vitamin C component is present in an amount of about 20 μg/ml to about 80 μg/ml, most preferably 20 to 50 μg/ml and the vitamin E component is present in an amount of greater than about 500 μg/ml, preferably greater than about 800 μg/ml, and most preferably greater than 1000 μg/ml.

-The whey protein is present in the compositions of the invention in an amount of about 50 to about 10,000 μg/ml, preferably about 750 to about 5,000, and most preferably about 1,000 μg/ml. The vitamin A component is typically present in an amount of from about 1 to about 100 μg/ml, more preferably from about 2 to about 20 μg/ml, and most preferably from about 3.5 to about 5.0 μg/ml.

The whey protein-containing compositions can be combined with a cosmetically and/or pharmaceutically acceptable carrier. The term "pharmaceutically or cosmetically acceptable carrier" refers to a vehicle, for either pharmaceutical or cosmetic use, which vehicle delivers the active components to the intended target and which will not cause harm to humans or other recipient organisms. As used herein, "pharmaceutical" or "cosmetic" will be understood to encompass both human and annual pharmaceuticals or cosmetics. Useful carriers include, example, water, acetone, ethanol, ethylene glycol, propylene glycol, butane- 1,3-diol, isoprop l myristate, isopropyl palmitate, or mineral oil. Methodology and components for formulation of cosmetic and pharmaceutical compositions are well known, and can be found, for example, in Remington's Pharmaceutical Sciences. Eighteenth Edition, A.R. Gennaro, Ed., Mack Publishing Co. Easton Pennsylvania, 1990.

The carrier may be in any form appropriate for topical application to the skin, such forms include but are not limited to for example, solutions, colloidal dispersions, emulsions (oil-in- vvater or water-in-oil), suspensions, creams, lotions, gels, foams, mousses, sprays and the like. The collagen synthesis enhancing compositions can be prepared in any form convenient for topical application to the skin. As will be apparent, the composition can be a therapeutic product, the whey protein, vitamin A component, v itamin E component and vitamin C component being the sole actives. The compo jitions of the present invention may also comprise additional useful active ingredients which include, but are not limited to antioxidants, antimicrobials, analgesics, anesthetics, anti-acne agents, antidermatitis agents, antipruπtic agents, anti-inflammatory agents, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoπatic agents, antiseborrheic agents, antiaging agents, antiwrinkle agents, skin lightening agents, depigmenting agents, wound-healing agents, corticosteroids, additional tanning agents, or hormones The incorporation of the active in the formulation is determined by its solubility and/or stability therein

The formulation, in addition to the carrier and the essential component mixture, also can comprise other components which may be chosen depending on the carrier and/or the intended use of the-formulation Additional components include, but are not limited to, water soluble colorants (such as FD&C Blue # 1 ). oil soluble colorants (such as D&C Green #6), water soluble sunscreens (such as Eusolex 232), oil soluble sunscreens (such as octyl methoxycmnamate) paniculate sunscreens (such as zinc oxide), antioxidants (such as BHT), chelatirg agents (such as disodium EDTA). emulsion stabilizers (such as carbomer). preservatives (such as methy l paraben). fragrances (such as pinene). flavoring agents (such as sorbitol), humectants (such as glycerine), waterproofing agents (such as PVP/eicosene copolymer), water soluble film-formers (such as hydroxypropy l methy lcellulose). oil-soluble film formers (such as hydrogenated C-9 resin), cationic polymers (such as polyquaternιum- 10). anionic polymers (such as xanthan gum) v itamins, and the like

The present invention also in udes methods of enhancing the synthesis of collagen in skin m which an effectiv e amount of the hey protein-containing compositions is applied to the skin The compositions of the inv ention can be applied on an as-needed basis, for example, they can be applied to the skin before anticipated prolonged sun exposure, or during or after such exposure Howev er, a preferred method of obtaining the benefits of the composition is via chronic topical application of a safe and effective amount of a composition containing the mixture, to prevent the onset of undesirable effects of a reduction in collagen in the skin or the development of skin damage which may occur naturally or may result from exposure to UV light or other env ironmental insults which may in turn result in the degradation of collagen, or prevent worsening of or rev erse existing damage It is suggested, as an example, that topical application be w ithin a range of from about once per week to about 4 or 5 times daily, preferably from about 3 times a week to about 3 times daily , most preferably about once or twice per day By "chronic" application, it is meant herein that the period of topical application may be over the lifetime of the user, preferably for a period of at least about one month, more preferably from about three months to about twenty years, more preferably from about six months to about ten years, more preferably still from about one year to about five years, thereby resulting in the treatment or prevention of the external signs of photoaging It will be recognized by those skilled in the art that the treatment regimen employed can be varied depending upon the user's level of exposure to noxious stimuli, a chronically sun-exposed individual may benefit from more frequent applications than will be necessary for an individual who avoids the sun

In another embodiment, the composition combines one or more sunscreens with the active components The combination may be with any sunscreen Examples of sunscreens useful in the compositions include, but are not limited to, inorganic sunscreens such as titanium and zinc oxides, or organic sunscreens such as para-amino benzoic acid (PABA) and its esters, benzophenones, pheny l or homomenthyl salicylates, and cinnamates In such a composition, the sunscreen of choice is employed in an amount consistent with the established use of that sunscreen

The hey protein-containing compositions of the present invention can also be a makeup product, for example, a lipstick, foundation, concealer, bronzer, blush, eyeshadow and the like Various other optional ingredients may be included with the whey protein-containing compositions of the present invention, these include but are not limited to fragrants, perfumes, flavorings, preservatives emollients antiseptics, pigments, dyes, colorants, humectants, propellants waterproofing agents, film formers v itamins as well as other classes of materials whose presence may be cosmeticalh pharmaceutically, medicinally or otherwise desirable Common examples can be found in the CTFA International Cosmetic Ingredient Dictionary 4th Edition The Cosmetic Toiletry, and Fragrance Association, Inc , Washington, D C , 1991 , the contents of which are incorporated herein

The invention is further illustrated by the following non-limiting example

EXAMPLES

1 Preparation of a hey protein-containing composition

The hey protein is prepared by a series of steps First, whey is produced as a byproduct of the manufacturing of cheese and is isolated The whey supply is initially purified using a claπfier which removes fine pieces or particles of cheese and casein An additional purification step involves ultrafiltration to separate the whey protein from lactose and other low molecular weight components in the w ev Next the whey protein is purified by diafiltration Purified water is used to wash out lactose and minerals Finally, the whey protein is dried at low temperatures with a high velocity spray dryer The resulting whey protein is a dry fine white powder

Vitamins A, C, and E are added in amounts according to the present invention to the appropriate formulation chosen based on its desired use as a product to achieve the additional effect of enhanced collagen synthesis

II Collagen synthesis activity of whey protein and vitamins A, E and C

Experiments are done examining the effectiveness of the whey protein and vitamin C, individually and various combinations of whey protein, vitamins C, A and E, as collagen synthesrs enhancers The results are illustrated in Figure 1 and the corresponding resultant numerical data demonstrating the percent increase in collagen synthesis (over media control) is provided in Table 1 below where W P is whey protein, V-C is vitamin C, V-E is vitamin E, and V-A is v itamin \ The numbers after each active component represent the amount of the active component in units of μg/ml In the absence of v itamin A, changes in levels of vitamin C have little effect on collagen sv nthesis This is true for both v itamin C alone and vitamin C in combination w ith the whev protein (see Table 1 % Increase for Samples 2) V-C 50, 3) V-C 100, 4) W P V-C 50. and 5) W P/V-C 100 below )

Table

-It is surprising and unexpected to find that a combination of vitamin A, vitamin C and whey protein and the higher level of vitamin E results in a greater percent increase in production of collagen than vitamin E at the lower level because there is little effect on the level of collagen produced when the amount of vitamin C alone or in combination with the whey protein is doubled from 50 μg/ml to 100 μg/ml. The present invention is most surprising in light of the decrease in collagen synthesis when vitamin C is doubled from 50 μg/ml (336% synthesis) to 100 μg/ml in the presence of v itamin E at the high level of 1000 μg/ml ( 132% synthesis) and the other components.

A study is done to examine the effect of the combination of vitamin A, vitamin C, v itamin E and whey protein as a collagen sy nthesis enhancer The three factors, vitamin A, v itamin C and vitamin E, are tested at high and low levels in a 2 " factorial design. For vitamin A, the high and low levels are 5 μg'ml and w ithout: for v itamin C, the high and low levels are 100 and 50 μg/ml; and for vitamin E, the high and low levels are 1 ,000 and 500 μg/ml. Uniform conditions are maintained with respect to the whey protein which is in an amount of 1,000 μg/ml.

Each treatment combination of the factorial is tested in triplicate. AH results are studied using known statistical methods of analysis. Analysis of the results of the designed experiment indicates that vitamin C and vitamin E are main effects and that there is an interaction between them in the presence of vitamin A and whey protein. Within specific ranges of vitamin E and vitamin C. in the presence of vitamin A and the whey protein, an inverse effect as a collagen synthesis enhancer is found.

Claims

What we claim is:

1. A topical composition comprising collagen enhancing effective amounts of a whey protein, a retinoid, a vitamin E or derivatives thereof and an ascorbic acid or derivatives thereof, said vitamin E being in an amount of less than 800 μg/ml and said ascorbic acid being in an amount of from about 20 μg/ml to about 200 μg/ml and less than said amount of vitamin E.

2. The composition of Claim 1 wherein said whey protein is present in an amount of from about 50 μg/ml to about 10,000 μg/ml.

3. -The composition of Claim 2 wherein said whey protein is present in an amount of from about 750 μg/ml to about 5,000 μg/ml.

4 The composition of Claim 1 w herein said retinoid is vitamin A.

5. The composition of Claim 4 wherein said retinoid is present in an amount of from about 1 μg/ml to about 100 μg/ml.

6. A collagen enhancing topical composition comprising an amount of vitamin E or derivativ es thereof less than 800 μg/ml. an amount of ascorπc acid or derivatives thereof from about 20 to about 200 μg ml. an amount of w hey protein from about ^"50 to about 5,000 μg/ml, and an amount of retinoid from about 1 to about 100 μg/ml, said amount of ascorbic acid being less than said amount of vitamin E.

7. A topical composition comprising collagen enhancing effective amounts of a whey protein, a retinoid, a vitamin E or derivatives thereof and an ascorbic acid or derivatives thereof, said vitamin E being in an amount of greater than 500 μg/ml and ascorbic acid being in an amount of from about 20 μg/ml to about 80 μg/ml.

8. The composition of Claim 7 wherein said whey protein is present in an amount of from about 50 μg/ml to about 10.000 μg/ml.

9 The composition of Claim 8 wherein said whey prot n is present in amount of from about 750 μg/ml to about 5,000 μg/ml

10 The composition of Claim 7 wherein said retinoid is vitamin A

1 1 The composition of Claim 10 wherein said retinoid is present in an amount of from about 1 μg/ml to about 100 μg/ml

12 A topical composition comprising an amount of vitamin E or derivatives thereof greater than about 800 μg/ml, an amount of ascorbic acid or derivatives thereof from about 20 to about 200 μg/ml, an amount of whey protein from about 750 to about 5,000 μg/ml, and an amount of retinoid from about 1 to about 100 μg/ml

13 A collagen enhancing topical composition comprising an amount of vitamin E or derivatives thereof from about 300 to about 800 μg/ml an amount of ascorbic acid or derivatives thereof from about 80 to about 200 μg/ml, an amount of whey protein from about 750 to about 5,000 μg/ml, and an amount of retinoid from about 1 to about 100 μg/ml

14 A collagen enhancing topical composition comprising an amount of vitamin E or derivativ es thereof from about 800 to about 1200 μg/ml. an amount of ascorbic acid or derivatives thereof from about 20 to about 80 μg/ml an amount of whey protein from about 750 to about 5 000 μg/ml, and an amount of retinoid from about 1 to about 100 μg/ml

15 A method of enhancing collagen synthesis in the skin comprising applying to the skin a topical composition comprising a collagen enhancing effective amount of a whey protein, vitamin A, vitamin E or derivatives thereof and vitamin C or derivatives thereof, said vitamin C being present in an amount of about 20 μg/ml to about 80 μg/ml and said vitamin E being present in an amount greater than 500 μg/ml

16 The method of Claim 15 wherein the composition comprises from about 50 μg/ml to about 5 000 μg/ml of the whey protein

17. The method of Claim 15 wherein the composition comprises from about 1 μg/ml to about 100 μg/ml of the vitamin A.

18. A method of enhancing collagen synthesis in the skin comprising applying to the skin a topical composition comprising a collagen enhancing effective amount of a whey protein, vitamin A, vitamin E or derivatives thereof, and vitamin C, or derivatives thereof, said vitamin C being present in an amount of about 20 μg/ml to about 200 μg/ml and said vitamin E being present in an amount less than 800 μg/ml.

19. The method of Claim 18 wherein the composition comprises from about 50 μg/ml to about 5, 500 μg/ml of the whey protein.

20. The method of Claim 18 wherein the composition comprises from about 1 μg/ml to about 100 μg/ml of the vitamin A.

21. A method of enhancing the synthesis of collagen in skin comprising applying to the skin a collagen enhancing effective amount of the composition of Claim 1.