Topical compositions for inhibiting matrix metalloproteases and providing antioxidative activities

FIELD OF THE INVENTION

The present invention generally relates to a composition for topical application. Specifically, a cosmetic or dermapharmaceutical composition is provided for antioxidative activities and immediate and delayed inhibition of matrix metalloprotease (MMPs) upon topical application thereof and thereby reducing and preventing wrinkles and damage of the skin.

BACKGROUND OF THE INVENTION

Lines and wrinkles on the skin are caused by degenerative changes in the proteins of the dermal extracellular matrix. They are signs of both chronologically-aged and photo-aged skin. In the past years, chronological aging and photo-aging were classified as different phenomena. However, in recent years, researchers have discovered some common molecular mechanisms between the two. Such mechanisms include decreased synthesis of new collagen, decreased anti-oxidative activities, and increased amount of matrix metalloproteases (MMPs).

MMPs are members of the zinc-dependent endopeptidases family. To date, there are over twenty known MMPs, each labeled in a general format "MMP-x," wherein x.gtoreq.1. The MMP gene family can be divided according to their substrate specificity and structure into subgroups of collagenases, gelatinases, stromelysins, matrilysin, enamelysin, membrane-type MMP, and others. For example, MMP-1 is a collagenase, MMP-3 is a stromelysin, and MMP-9 is a gelatinase.

One major biological function of MMPs is to catalyze the breakdown of macromolecules in the extracellular matrix such as collagen and elastin. The breakdown of dermal collagen and elastin is purported to be one of the major contributing factors to loss of skin's firmness and elasticity. Such changes cause the skin to appear aged (i.e., dull, wrinkled, and saggy). Thus, it is of great importance to reduce, if not completely block, the enzymatic activity of MMPs.

In fact, human tissues are capable of naturally producing inhibitors of MMPs known as tissue inhibitors of matrix metalloproteases (TIMPs). At present, the TIMP gene family consists of four members: TIMP-1, TIMP-2, TIMP-3, and TIMP-4. TIMPs are capable of reversibly inhibiting the MMPs in a 1:1 stoichiometric fashion. A more detailed and comprehensive review of MMPs and TIMPs has been presented by Woessner and Nagase in Matrix Metalloproteinases and TIMPs, Oxford University Press, 2000. In addition to their inhibitory role against MMPs, TIMPs are also able to promote cell proliferation in a wide range of cell types and may have an anti-apoptotic function. This indicates that TIMPs may be able to serve as MMP inhibitors as well as skin regenerators. Unfortunately, the biological production of TIMPs decreases with aging, while the production of MMP increases, thereby contributing to the aging of the skin. Thus, it is desirable to supplement the depleted TIMPs by delivering to the skin inhibitors of MMP.

To date, a number of agents have been studied for their potency as MMP inhibitors. For example, it has been demonstrated that the topical application of epigallocatechin-3-gallate or retinoic acid to a skin tissue model prior to UVA irradiation prevents an increase in MMP-1 (interstitial collagenase) expression and activity. (Jong Hee Lee, et al., The Effects of Epigallocatechin-3-gallate on Extracellular Matrix Metabolism, Journal of Dermatological Science, 40(3); 195-204 (December 2005)). Similarly, 2',4',7-trihydroxyisoflavone, also prevents increases in UV-induced MMP-1 activity in cultured fibroblasts. Other examples of MMP inhibitors are described and studied as CT1166 and RO31-7467 by Hill et al. (Peter A. Hill, et al., Inhibition of Bone Resorption In Vitro by Selective Inhibitors of Gelatinase and Collaginase, Biochemical Journal, 308; 167-175 (1995)).

Of the MMP inhibitors studied, some are used in topical cosmetic compositions to counteract the effect of photo- and chronological skin aging. For example, certain di-peptide analogs with fused or conjugated bicycloaryl substitutes are potent broad-spectrum hydroxamate inhibitors of MMPs. One example of such di-peptides is Galardin (INCI name: N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide), the structure of which is shown below:

##STR00001##

Galardin inhibits MMP activities by interacting with the zinc atom in the active site of MMPs. Another example of commercially available MMP inhibitor is Pepha.RTM.-TIMP available from Pentapharm AG. Pepha.RTM.-TIMP is TIMP-2 which exhibits strong inhibitory effect towards MMP-1, but also effective against MMP-2, MMP-3, MMP-8, and MMP-9.

Furthermore, the use of MMP inhibitors in combination with other anti-aging cosmetic agents is known in the art. For example, the use of UV blockers (e.g. octinoxate and zinc oxide) in combination with an MMP inhibitor for inhibiting photoaging of skin is known. Cosmetic compositions including an MMP inhibitor and a natural estrogen (e.g., 17-beta estradiol or an estrogen-like steroid) have also been reported to diminish skin wrinkles and fine lines.

Another example of agents known to be combined with MMP inhibitors is antioxidants. Antioxidants are molecules or complexes that are capable of slowing or preventing the oxidation of other biomolecules caused by free radicals and reactive oxygen species. Damages to healthy cells caused by such harmful agents are a major contributor to wrinkles and precancerous cell changes in the skin. In fact, human body is capable of producing natural antioxidants. One example is superoxide dismutase ("SOD"), an enzyme that neutralizes superoxide free radical (.O.sub.2.sup.-), which is the most common free radical in the body that can damage other important enzymes, membrane lipids, and nucleic acids. Additionally, SOD promotes cell repair and production of functional fibroblasts in the dermis. However, the SOD levels decrease with age. Thus, much of dermapharmaceutical compositions known in the art have been combining MMP inhibitors and antioxidants in an effort to replenish the body's deficiency of such anti-aging agents.

However, a common shortcoming of aforementioned cosmetic compositions comprising MMP inhibitors and anti-aging agents is that they provide short-term MMP inhibitory and antioxidative activities. Such compositions temporarily reverse or reduce the skin damage caused by MMPs, but they must be frequently reapplied to the skin for a lasting anti-aging effect. This is impractical and uneconomical from the consumers' perspective. Thus, researchers are now looking to agents with long-term anti-aging effect that stimulate the body's production of endogenous MMP inhibitors (i.e., TIMPs) and/or SOD.

The up-regulation of TIMP gene in the skin is considered as a form of long-term "anti-aging" mechanism, because an increase in the number of TIMPs contributes to the reduction of MMPs' destructive activities. The human body is capable of up-regulating the expression of TIMP genes by various cytokines. For example, the production of TIMP-1 and TIMP-3 are enhanced by a cytokine called Transforming Growth Factor beta (TGF-.beta.). (Laura Mattila et al., Activation of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) mRNA Expression in Scleroderma Skin Fibroblasts, The Journal of Investigative Dermatology, 110(4); 416-421 (April 1998); and Kanako Kikuchi et al., Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) May be an Autocrine Growth Factor in Scleroderma Fibroblasts, The Journal of Investigative Dermatology, 108(3); 281-284 (March 1997)). TIMP-2 has been shown to be induced by another type of cytokine called interleukin-4 (IL-4). (Ihn et al., IL-4 Up-Regulates the Expression of Tissue Inhibitor of Metalloproteinase-2 in Dermal Fibroblasts via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway, The Journal of Immunology, 168; 1895-1902 (February 2002)). However, products providing such long-term effects alone are inadequate to attract consumers who are interested to see immediate results.

Thus, it is desirable to provide a topical composition that provides a long-term anti-aging benefits to the skin comprising an agent that induces TIMP production ("TIMP inducing agent") and an agent that induces SOD production ("SOD inducing agent"). There is also a need for a topical composition that further provides short-term anti-aging benefits to the skin comprising an MMP inhibitor. Similarly, there is a need for topical composition that incorporates SOD inducing agents and antioxidants for both a long-term and short-term protection from free radical damage to the skin. During our endeavor to create an effective anti-aging composition having long-term and short-term anti-aging effects, it has been unexpectedly discovered that the combination of an MMP inhibitor(s), a TIMP inducing agent(s), an antioxidant(s), and an SOD inducing agent(s) provides a remarkably synergistic antioxidative and MMP inhibitory activity, thereby providing powerful anti-aging effects on the skin.

SUMMARY OF THE INVENTION

The present invention is directed toward topical compositions that diminish skin wrinkles, fine lines and improve skin tones. More specifically, the present invention provides topical compositions for use as a topical skin care regimen that preferably combine at least one matrix metalloprotease inhibitor ("MMP inhibitor") component, at least one tissue inhibitor of metalloprotease ("TIMP") inducing agent, and at least one natural extract, such as a plant, fungus, and/or fruit extract. Such combination of agents provides synergistic anti-aging effects to the skin. More preferably, the MMP inhibitor component comprises Glycine soja (soybean) seeds extract, TIMP inducing agent comprises acetyl hexapeptide-20, and the natural extract is selected from the group consisting of Tremella fuciformis (snow fungus) extract, Eugenia caryophyllus (clove) extract and Camellia sinensis (green tea) extract, Pyrus malus (apple) fruit extract, Cinnamomum cassia (cinnamon) Bark extract, Rheum palmatum (Chinese rhubarb) extract, and combinations thereof.

Without being limited thereto, the topical composition of the present invention may be in the form of gel, lotion, oil-in-water or water-in-oil emulsions, water-in-silicone emulsions, hydroalcoholic systems, aerosol, spray or anhydrous form.

It is an object of the present invention to provide topical compositions that provide short-term MMP inhibiting and antioxidative activities.

It is another object of the present invention to provide topical composition that stimulates the body's production of TIMP and superoxide dismutase (SOD), promoting long-term anti-aging effects.

It is another object of the present invention to provide topical composition that provides long-term antioxidative activities.

It is another object of the present invention to provide topical compositions having at least one MMP inhibitor.

It is another object of the present invention to provide topical composition that is effective to inhibit a broad spectrum of matrix metalloprotease, including MMP-1, MMP-3 and MMP-9.

It is another object of the present invention to provide topical compositions having a tissue inhibitor of matrix metalloprotease (TIMP) inducing agent.

It is another object of the present invention to provide topical compositions comprising various natural extracts providing antioxidative and MMP inhibiting effects.

It is another object of the present invention to provide topical compositions having at least one MMP inhibitor, a TIMP inducing agent, and natural extract component having high concentration of antioxidants.

It is another object of the present invention to provide topical compositions for use in anti-wrinkle and/or anti-aging cosmetic compositions.

It is another object of the present invention to provide topical compositions that provide elasticity, firmness, tone and texture to the skin.

It is another object of the present invention to provide topical compositions that ameliorate fine lines and prevent photo-damage of the skin.

BRIEF DESCRIPTION OF THE FIGURES

A further understanding of the present invention can be obtained by reference to a preferred embodiment, along with some alternative embodiments, set forth in the illustrations of the accompanying figures. Although the illustrated embodiments are merely exemplary of systems for carrying out the present invention, the organization and method of operation of the invention in general, together with further objectives and advantages thereof, may be more easily understood by reference to the figures and the following description. The figures are not intended to limit the scope of this invention, which is set forth with particularity in the claims as appended or as subsequently amended, but merely to clarify and exemplify the invention.

For a more complete understanding of the present invention, reference is now made to the following figures.

FIG. 1 illustrates a histogram representing the MMP inhibiting effect of a composition comprising an MMP inhibitor and natural extracts, a composition comprising a TIMP inducing agent and natural extracts, and the effect of a combination thereof in a 1:1 ratio.

FIG. 2 illustrates a histogram representing the total anti-oxidant potential (TAOP) of a composition comprising an MMP inhibitor and natural extracts, a composition comprising a TIMP inducing agent and natural extracts, and the effect of a combination thereof in a 1:1 ratio.

DETAILED DESCRIPTION OF THE INVENTION

Detailed illustrative embodiments of the present invention are disclosed herein. However, the present invention may be embodied in a wide variety of forms, some of which may be quite different from those in the disclosed embodiments. Consequently, the specific ingredients and functional details disclosed herein are merely representative, yet in that regard, they are deemed to afford the best embodiments for purposes of disclosure and to provide a basis for the claims herein which define the scope of the present invention.

Moreover, well known methods and procedures for both carrying out the objectives of the present invention and illustrating the preferred embodiments are incorporated herein by reference but have not been described in detail as not to unnecessarily obscure aspects of the present invention.

The present invention relates to topical compositions providing short-term and long-term anti-aging effects to the skin. By combining an MMP inhibitor component and a TIMP inducing agent in the topical composition, the present invention promotes skin's short-term healing, as well as body's natural generation of TIMPs for prolonged MMP inhibiting effects. Furthermore, the incorporation of natural extract component in the present invention aids in the synergic anti-aging effects of the topical compositions. Therefore, the topical composition restores photo-aged and chronologically-aged skin by providing elasticity, firmness, tone and texture to the skin, while ameliorating fine lines and wrinkles.

MMP Inhibitor Component

The MMP inhibitor component of the topical composition comprises at least one MMP inhibitor that provides a short-term anti-aging effect. The amount of the MMP inhibitor component may be adjusted such that a final cosmetic product comprises from about 0.001% to about 1.0% by weight of the MMP inhibitor component. It is contemplated that MMP inhibitors encompass various agents that are capable of directly or indirectly retarding the catabolic function of at least one type of MMP. Preferably, the topical composition of the present invention comprises an MMP inhibitor that is effective to inhibit a broad spectrum of MMP, including MMP-1, MMP-3 and MMP-9. Furthermore, the MMP inhibitors need not completely inhibit the activity of target MMPs to be effective. It is enough that some inhibition of the target MMPs occurs.

Preferably, the MMP inhibitor component comprises Glycine soja (soybean) seeds extract, which contains a soy peptide complex. The soy peptide complex has been specially formulated to provide maximal MMP inhibitory activity. The soy peptide complex is effective for inhibiting at least MMP-1, MMP-3, and MMP-9 and prevents these MMPs from degrading dermal macromolecules, such as collagen and elastin. The soy peptide complex also provides essential amino acids for the synthesis of skin collagen and interacts synergistically with other components to improve skin conditions and provide anti-aging benefits.

Other commercially available MMP inhibitors that may be useful in the topical composition of the present invention may be used. For example, Galardin (INCI name: N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide) is a dipeptide MMP inhibitor that directly interacts with the active sites of MMPs. On the other hand, other types of MMP inhibitors, such as farnesyl transferase inhibitors (farnesyl acetate and (.alpha.-hydroxyfarnesyl) phosphoric acid) prevent expression of certain MMPs by interfering with signal transduction pathways for UVB-inducible MMPs (U.S. Pat. No. 5,837,224). Other commercially available MMP inhibitors that may be used in the topical composition of the present invention include, but are not limited to Batimastat (IUPAC name: (2S,3R)--N-hydroxy-N'-[(1S)-1-(methylcarbamoyl)-2-phenyl-ethyl]-3-(2-meth- ylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide), Marimastat (IUPAC name: N-[2,2-dimethyl-1-(methylcarbamoyl)propyl]-2-[hydroxy-(hydroxycarba- moyl)methyl]-4-methyl-pentanamide), Galardin (INCI name: N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide), Colhibin (INCI name: hydrolyzed rice protein, glycerin, water), Pepha.RTM.-TIMP (INCI name: Tissue Inhibitor of Metalloproteinases 2), Syn.RTM.-Coll (INCI name: palmitoyl tripeptide-5, glycerine), Trylagen.RTM. (INCI name: water, Pseudoalteromonas ferment extract, hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide-10 citrulline, tripeptide-1, Lecithin, xantham gum, carbomer, triethanolamine, caprylyl glycol), Ilomastat (INCI name: N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide), and combinations thereof. Marimastat and Batimastat are available from British Biotech Ltd. Colhibin, Pepha.RTM.-TIMP, and Syn.RTM.-Coll are available from Pentapharm AG. Trylagen.RTM. can be purchased from Lipotec, S.A. and Ilomastat is available from Chemicon International, Inc. Further examples of MMP inhibitors are those disclosed in U.S. Pat. Nos. 5,183,900, 5,189,178, 5,239,078, 5,696,147, 5,837,224, 5,773,438, and 5,892,112, all of which are incorporated herein by reference.

Natural Extract Component

The topical composition of the present invention further comprises a natural extract component. The natural extract component may comprise an extract derived from a plant, fruit, fungus, or a mixture thereof. The amount of a natural extract component may be adjusted such that a final cosmetic product comprises from about 1.0% to about 25% by weight of natural extract component. The natural extract component preferably has high antioxidative capacity, MMP inhibitory activity, and SOD inducing ability, thereby providing both short-term and long-term anti-aging benefits to the skin. The short-term anti-aging effects are caused by agents that are antioxidants and/or MMP inhibitors. Antioxidative agents often contain effective reducing agents such as polyphenols, glutathione, vitamin C, and vitamin E. The long-term anti-oxidative benefits are provided by certain agents that are capable of either stimulating the production of body's endogenous antioxidants (e.g. superoxide dismutase) or enhancing the activity of such endogenous antioxidants. The natural extract(s) used in the present invention may be obtained through conventional methods known in the art, such as solvent extraction, distillation, enfleurage, and ram press method.

Preferably, the natural extract component may comprise Eugenia caryophyllus (clove) extract. Clove extract not only acts as a MMP inhibitor, but also believed to be one of nature's most powerful antioxidant. Eugenia caryophyllus (clove) extract is an example of the short-term anti-aging agent. It is preferably prepared by liquid extraction in glycerin and water. Clove extract is a potent MMP inhibitor and Human Neutrophil Elastase inhibitor, which in turn protects the extra-cellular matrix from enzymatic degradation. It can be purchased from Biocogent, Ltd. under the trade name Scavenox.TM. Clove Extract. Clove extract is known to have superior antioxidative effects to most other natural extracts. Major active ingredients in clove extracts include gallic acid derivatives and eugenol/eugenol acetate. Gallic acid acts as an antioxidant and helps to protect cells against oxidative damage. It is found to show cytotoxicity against cancer cells without harming healthy cells. Eugenol and eugenol acetate are main aroma constitutes of clove extract. They are also well known for their antioxidative, anti-fungal, and antimicrobial properties. Combined with the clove extract's potent MMP inhibitory capacity, these activities provide strong anti-inflammatory performance, which enhances the skin texture and ultimately contributes to the overall health of the skin.

Preferably, the natural extract component may further comprise Camellia sinensis (green tea) extract. Green tea extract has high content of polyphenols (flavonoids), including gallocatechin, epigallocatechin, epictechin, and epigallocatechin gallate. These polyphenols have been shown to inhibit UVB-induced expression of MMP-2, MMP-3, MMP-7, and MMP-9 in hairless mouse skin. (Praveen K. Vayalil, et al., Green Tea Polyphenols Prevent Ultraviolet Light-Induced Oxidative Damage and Matrix Metalloproteinases Expression in Mouse Skin, Journal of Investigative Dermatology, 122: 1480-87 (2004)). Furthermore, green tea extract is a great source of antioxidant. Green tea extract interacts with and inhibits reactive oxidation species (ROS). Comparative UV-lipid peroxidation studies indicate that green tea polyphenols are extremely effective in reducing/inhibiting UV-induced photo-oxidation and protecting cells from free radical damage. As with clove extract, green tea extract used in the present invention is preferably prepared by liquid extraction in glycerin and water. It can be purchased from Biocogent, Ltd. under the trade name Scavenox.TM. Green Tea Extract.

Preferably, the natural extract component may comprise an extract of Tremella fuciformis (snow fungus), also known as white fungus or silver tree-ear fungus--a type of jelly fungus used in Chinese traditional medicine and cuisine. Polysaccharides of Tremella fuciformis exert a long-term anti-aging effect by increasing the superoxide dismutase (SOD) production in the skin. (Zhou et al., Anti-Aging Effect of the Polysaccharides from Auricularia Auricular and Tremella Fuciformis, Journal of China Pharmaceutical University, 20; 303-6 (1989)). Superoxide dismutase is the body's natural antioxidant for reducing free radical damage to the skin. In U.S. Pat. No. 5,547,672, extracts of the snow fungus have been used as a pharmaceutical agent for treatment of wounds and other skin injuries.

Preferably, the natural extract component may further comprise Pyrus malus (apple) fruit extract. Apple fruit extract boosts the antioxidative activities of the cosmetic composition and aids in the synergic anti-aging effects of the topical composition. Apple fruit extract contains powerful anti-inflammatory agents called terpenoids. Terpenoids, such as ursolic acid, inhibit human leukocyte elastase, 5-lipoxygenase, and cyclooxygenase activities. These effects prevent the generation of inflammatory mediators. (Qi-Long Ying et al., Inhibition of Human Leucocyte Elastase by Ursolic Acid, Biochemistry Journal, 277; 512-16 (1991)). In addition to its anti-inflammatory properties, ursolic acid also provides amelioration for photo-aged skin by stimulating skin collagen and epidermal cell ceramide synthesis. Ursolic acid helps to reduce the appearance of wrinkles and age spots by restoring the skin's collagen structure and elasticity. A detailed discussion of the mechanism can be found in J. Liu, Pharmacology of Oleanolic and Ursolic Acid, Journal of Ethnopharmacology, 49; 57-68 (1995).

Preferably, the natural extract component may further comprise Cinnamomum cassia (cinnamon) bark extract. Cinnamon bark extract boosts the antioxidative activities of the cosmetic composition and aids in the synergic anti-aging effects of the topical composition.

Preferably, the natural extract component may further comprise Rheum palmatum (Chinese rhubarb) extract. Chinese rhubarb extract boosts the antioxidative activities of the cosmetic composition and aids in the synergic anti-aging effects of the topical composition.

Quercus rubra (red oak) bark extract is yet another good source of antioxidant. Red oak bark extract contains tannins, which are readily absorbed into damaged skin. Tannins are highly astringent compounds that act locally by precipitating proteins to the wounds, decreasing cell membrane permeability and exerting anti-inflammatory and anti-bacterial properties. In U.S. Pat. No. 5,080,900, an aqueous extract of oak bark ash has been used for treatment of skin ulcers.

Other examples of natural extracts having antioxidative benefits that may be used in the topical composition of the present invention include, but are not limited to Ginkgo biloba extract, Black chokeberry (Photinia melanocarpa) extract, Cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract, Bilberry (Vaccinium myrtillus L.) extract, French maritime pine (Pinus pinaster) extract, Milk thistle (Silybum marianum) extract, Caper (Capparis spinosa L.) extract, Culcitium reflexum leaf extract, Krameria triandra root extract, Peach (Prunus persica) flower extract, Great burnet (Sanguisorba officinalis L.) root extract, Autumn joy (Sedum telephium) leaf extract, Pueraria Lobata extract, lemon grass extract, basil extract, grape seeds extract, rosemary extract, sage extract, thyme extract, chamomile extract, lavender extract, horse chestnut extract, and lemon extract, Quercus rubra (red oak) bark extract, and combinations thereof.

Other examples of natural extracts having both antioxidative and MMP inhibitory activity that may be incorporated into the topical composition of the present invention include, but are not limited to Japanese Horse Chestnut (Aesculus turbinata Blume) extract, Argania spinosa leaf extract, Pariparoba (Pothomorphe umbellata) root extract, Marine eelgrass (Zostera marina L.) extract, Pomegranate (Punica granatum L.) extract, calaguala (Polypodium leucotomos) extract, blackberry (Rubus fruticosus) extract, raspberry extract, muscadine grapes extract, rooibos (Aspalathus linearis) extract, Pine (Pinus densiflora) pollen extract, Blackberry (Rubus fruticosus) leaf extract, and combinations thereof. Additionally, U.S. Application Publication No. 2007/0122492 discloses various plant extracts that are capable of inhibiting one or more extracellular proteases including MMP-1, MMP-2, MMP-3, MMP-9. All of such plant extracts are incorporated herein by reference.

Preferably, the composition of the present invention comprises a combination of an MMP inhibitor component and a natural extract component for providing short term antioxidative and MMP inhibiting activities. The relevant amounts of each ingredient may be adjusted such that a final cosmetic product comprises from about 0.001% to about 1.0% by weight of the MMP inhibitor component and from about 1.0% to about 25% by weight of natural extract component. An illustrative example of such combination is PreAge (available from BASF Corporation). PreAge generally comprises Glycine soja (soybean) seed extract as the MMP inhibitor component, and Pyrus malus (apple) fruit extract, Cinnamomum cassia (cinnamon) bark extract, and Rheum palmatum (Chinese rhubarb) as short-term anti-aging agents of the natural extract component. Optionally, other suitable cosmetic adjuvants known in the art may be also added to PreAge. One embodiment of PreAge is shown in the following table:

TABLE-US-00001 TABLE 1 Percentage by PreAge Ingredients weight (%) Pyrus malus (apple) fruit extract 4% Glycine soja (soybean) seed extract 1% Cinnamomum cassia (cinnamon) Bark Extract 1% Rheum palmatum (Chinese rhubarb) extract 1% Butylene Glycol 93% Total 100%

PreAge may be included in the final cosmetic products in the range from about 0.1% to about 5.0% by weight, preferably from about 1.0% to about 4.0% by weight.

TIMP Inducing Agent

Preferably, the composition of the present invention comprises a long-term anti-aging agent. Preferably, the long-term anti-aging effect is provided by at least one TIMP inducing agent. The amount of TIMP inducing agent should be adjusted such that a final cosmetic product comprises from about 0.01% to about 2.00% by weight of a TIMP inducing agent. TIMP inducing agent is a molecule or a complex that enhances the activity of TIMPs and/or up-regulates the production of TIMPs by human body. TIMPs are main regulators of the activity of MMPs. Preferably, the TIMP inducing agent comprises an elastin-derived synthetic peptide acetyl hexapeptide-20. Acetyl hexapeptide-20 of the present invention is able to stimulate the production of endogenous MMP inhibitors (i.e., TIMPs). In addition, acetyl hexapeptide-20 has shown the ability to trigger cellular processes that stimulate human skin fibroblasts proliferation. Fibroblasts synthesize the extracellular matrix including collagen and elastin. When adequately delivered into the dermis, acetyl hexapeptide-20 may mimic basic stimulatory and regulatory steps for collagen and extracellular matrix production, resulting in improvement of aged skin and prevention of intrinsic aging and photo-aging. Without being limited thereto, other suitable TIMP inducing agents may be used in the composition of the present invention.

Preferably, the composition of the present invention comprises a combination of a TIMP inducing agent and a natural extract component for providing long term antioxidative and MMP inhibiting activities. The relevant amounts of each ingredient may be adjusted such that a final cosmetic product comprises from about 0.01% to about 2.00% by weight of a TIMP inducing agent, and from about 1.0% to about 25% by weight of natural extracts. An illustrative example of such combination is Avantage.RTM. TE, available from Biocogent, Ltd. Avantage.RTM. TE generally comprises acetyl hexapeptide-20 as a TIMP inducing agent, Tremella fuciformis (snow fungus) extract as a long-term anti-aging agent of the natural extract component, and Eugenia caryophyllus (clove) extract and Camellia sinensis (green tea) leaf extract as short-term anti-aging agents of the natural extract component. Optionally, other suitable cosmetic adjuvants known in the art may be also added to this composition. Avantage.RTM. TE may be included in the final cosmetic products in the range from about 0.1% to 5% by weight, preferably about 1% to 4% by weight. One embodiment of Avantage.RTM. TE is shown in the following table:

TABLE-US-00002 TABLE 2 Percentage by Avantage .RTM. TE Ingredients weight (%) Acetyl Hexapeptide-20 1.25% Tremella fuciformis (snow fungus) extract 0.42% Eugenia caryophyllus (clove) extract 4.85% Camellia sinensis (green tea) leaf extract 2.20% Hydrolyzed soy protein 0.45% Potassium Sorbate 0.50% Sodium Benzoate 0.50% Germall 115 0.40% Glycerin 37.5% Water 51.93% Total 100%

Preferably, the composition of the present comprises the combination of PreAge and Avantage.RTM. TE. As a result, such a composition comprises an MMP inhibitor component, a TIMP inducing agent, and a natural extract component, which in combination will provide short term and long term antioxidative and MMP inhibiting activities. The ratio between PreAge and Avantage.RTM. TE can range from about 99:1 to about 1:99 by weight, preferably from about 9:1 to about 1:9 by weight, and more preferably at about 1:1 by weight. Such combined composition may be incorporated in a final cosmetic product in the range from about 0.1% to about 10%, preferably from about 1.0% to 8.0% by weight, and more preferably from about 2.0% to about 6.0% by weight.

The topical compositions of the present invention may further comprise pH adjusting agents, sunscreens, surfactants, emulsifiers, humectants, emollients, skin conditioning agents, pH preservatives, thickeners, solvents and other acceptable carriers, a mixture thereof, and other cosmetic adjuvants known in the art.

The compositions may also include one or more pH adjusting agents. None limiting examples of pH adjusting agents include ascorbic acid, citric acid, malic acid, sodium citrate, sodium hydroxide, lactic acid, and triethanolamine. In one embodiment of the present invention, 10% citric acid may be used as a pH agent. The pH of the topical compositions of the present invention preferably ranges from about 3.0 to about 8.0.

The composition of the present invention may comprise one or more sunscreens. A wide variety of sun screening agents are described in U.S. Pat. Nos. 5,073,371 and 5,073,372. Non-limiting examples of sunscreens are 2-ethylhexyl p-methoxycinnamate, 2-ethylhexyl N,N-dimethyl-p-aminobenzoate, p-aminobenzoic acid, 2-phenylbenzimidazole-5-sulfonic acid, oxybenzone, octyl salicylate, 4,4'-methoxy-t-butyldibenzolymethane, 3-benzylidene camphor, titanium dioxide, zinc oxide, iron oxide, and mixtures thereof.

The composition of the present invention may comprise one or more surfactants. Surfactants used in the instant invention can be anionic, cationic and amphoteric surfactants. Non-limiting examples of surfactants are alkylbenzene sulfonates, alkane sulfonates, olefin sulfonates, glycerol ether sulfonates, fatty acid isethionates, fatty alcohol/acid polyglycol ethers, alkoxylated triglycerides, polyol fatty acid esters, sugar esters, sorbitan esters, quaternary ammonium compounds, and betaines.

The composition of the present invention may comprise one or more emulsifiers. A wide variety of emulsifiers can be used, but not limited to, those selected from the group consisting of sorbitan esters, glyceryl esters, polyglyceryl esters, methyl glucose esters, sucrose esters, ethoxylated fatty alcohols, hydrogenated castor oil ethoxylates, polymeric emulsifiers and silicone emulsifiers.

The composition of the present invention may comprise one or more emollients. The term emollients, as used herein is intended to include conventional lipid materials (e.g., plant/animal fats, waxes and other water-insoluble materials), polar lipids, hydrocarbons, and silicone oils. Non-limiting examples of conventional emollients are C.sub.8-C.sub.30 alkyl esters of C.sub.8-C.sub.30 carboxylic acids; monoglycerides, diglycerides, and triglycerides of C.sub.8-C.sub.30 carboxylic acids, cholesterol esters of C.sub.8-C.sub.30 carboxylic acids, and hydrocarbons. Also useful as emollients are the so-called "polar lipids" which include C.sub.10-C.sub.20 alcohol sorbitan monoesters/diesters/triesters, C.sub.10-C.sub.20 fatty alcohol esters of hydroxy acids. Non-limiting examples of silicone emollients are dimethicone copolyol, polysiloxanes, dimethiconol, and mixtures thereof.

The composition of the present invention may comprise one or more humectants. Non-limiting examples of humectants are Aloe barbadensis leaf extract, betaines, glycerin, propylene glycol, 1,3-butylene glycol, hydrolyzed corn starch, hydroxylated jojoba oil, lactic acid, lysine PCA, maltose, polyglucuronic acid, Saccharomyces lysate extract, sodium PCA, sorbitol, urea, and mixtures thereof.

The composition of the present invention may comprise one or more skin conditioning agents. Non-limiting examples of skin conditioning agents include allantoin, biosaccharide gum, bisabolol, oligopeptides, dimethicone crosspolymer, beta-glucan, sunflower seed oil, linoleic acid, niacin, niacinamide, phospholipids, hydrolyzed soy protein, soy sterol, soy amino acids, sodium hyaluronate, tyrosine, wheat amino acids, and mixtures thereof.

The composition of the present invention may comprise one or more preservatives. Non-limiting examples of preservatives include benzylparaben, butylparaben, chlorhexidine digluconate, diazolidinyl urea, DMDM hydantoin, ethylparaben, imidazolidinyl urea, isobutulparaben, isopropylparaben, Methylparaben, phenyl benzoate, sodium salicylate, triclocarban, triclosan, zinc salicylate and mixtures thereof.

The composition of the present invention may comprise one or more viscosity increasing agents. Viscosity increasing agents can be both aqueous and non-aqueous. Non-limiting examples include acrylamides copolymer, acrylamide/sodium acrylate copolymer, acrylates/alkyl acrylate crosspolymer, beewax, carbomer, cetearyl alcohol, hydrogenated vegetable oils, hydropropyl starch phosphate, magnesium silicate, polyvinyl alcohol, sodium chloride, xanthan gum and mixtures thereof.

The topical compositions of the present invention can be used for the preparation of cosmetic and/or dermapharmaceutical products. Without being limited thereto, the topical composition of the present invention may be in the form of gel, lotion, cream, oil-in-water or water-in-oil emulsions, water-in-silicone emulsions, hydroalcoholic systems, aerosol, spray or anhydrous powder, stick, paste, or viscous liquid. It is contemplated that the topical composition can be applied on any parts of the body except the mucous membranes. Unlimited examples of such body parts to which the topical composition can be properly applied include hands, arms, legs, feet, trunk, and face including eyelids and lips.

The following Examples more fully illustrate selected embodiments of the present invention.

Example 1

Composition Comprising an MMP Inhibitor Component, a TIMP Inducing Agent and a Natural Extract Component

The composition according to the present invention providing both short-term and long-term anti-aging effects comprises an MMP inhibitor component, a TIMP inducing agent, and a natural extract component. An example of such MMP-inhibitory and antioxidative complex providing both short-term and long-term effects is shown in Table 3. The relative ranges of amounts of each ingredient in the complex are also provided.

TABLE-US-00003 TABLE 3 Short-Term and Long-Term Percentage Range MMP-Inhibitory and Antioxidative Complex by Weight (%) Glycine soja (soybean) seed extract 0.05%-1.50% Acetyl Hexapeptide-20 0.50%-2.50% Tremella fuciformis (snow fungus) extract 0.05%-1.50% Eugenia caryophyllus (clove) extract 0.50%-3.00% Camellia sinensis (green tea) leaf extract 0.50%-2.50% Cinnamomum cassia (cinnamon) Bark Extract 0.05%-1.50% Pyrus malus (apple) fruit extract 1.50%-3.00% Rheum palmatum (Chinese rhubarb) extract 0.05%-1.50% Other ingredients (Solvent, fragrance, Suitable amount to preservatives, etc.) balance 100% by weight

The composition according to Table 3 may be incorporated in a final cosmetic product in the range from about 0.1% to about 10%, preferably from about 1.0% to 8.0% by weight, and more preferably from about 2.0% to about 6.0% by weight.

One exemplary embodiment of a MMP-inhibitory and antioxidative complex providing both short-term and long-term effects is shown in Table 4. It was prepared in a conventional manner known in the art.

TABLE-US-00004 TABLE 4 Short-Term and Long-Term Percentage by MMP-Inhibitory and Antioxidative Complex weight (%) Glycine soja (soybean) seed extract 0.500% Acetyl Hexapeptide-20 0.625% Tremella fuciformis (snow fungus) extract 0.210% Eugenia caryophyllus (clove) extract 2.425% Camellia sinensis (green tea) leaf extract 1.100% Cinnamomum cassia (cinnamon) Bark Extract 0.500% Pyrus malus (apple) fruit extract 2.000% Rheum palmatum (Chinese rhubarb) extract 0.500% Other ingredients (Solvent, fragrance, 92.140% preservatives, etc.) Total 100.000%

The composition according to Tables 4 may be incorporated in a final cosmetic product in the range from about 0.1% to about 10%, preferably from about 1.0% to about 8.0% by weight, and more preferably from about 2.0% to about 6.0% by weight.

Example 2

Demonstration of MMP Inhibitory Effects of a Composition Comprising an MMP Inhibitor and a Natural Extract Component, a Composition Comprising a TIMP Inducing Agent and a Natural Extract Component, and the Effect of a Combination Thereof in a 1:1 Ratio Using FRET Assay-SensoLyte.TM.

In this test, the relative inhibitory capacities of compositions according to Tables 1, 2, and 4 against MMPs were studied using Fluorescence Resonance Energy Transfer (FRET). FRET has been used for the continuous assay of MMP activity and high-throughput screening of MMP inhibitors. The FRET assay used to analyze the composition according to the present invention was SensoLyte.RTM., available from AnaSpec, Inc. The test utilizes a feature of a FRET peptide (i.e., a generic MMP substrate), which emits fluorescence upon being cleaved by active MMPs. When the cleavage activity of MMPs is inhibited or suppressed by a test composition, (i.e., an MMP inhibitor), no or relatively less fluorescence is detected, depending on the degree of inhibition.

The test was performed in a standard 96-well microplate format. FRET peptides were diluted 1:100 in an assay buffer and added to the 96-well plate (50 .mu.L/well). The composition according to Table 1 ("Complex A") was prepared at concentrations of 1%, 2%, and 4% by weight in the assay buffer. Similarly, the composition according to Table 2 ("Complex B") was prepared at concentrations of 1%, 2%, and 4% by weight in the assay buffer. Finally, the composition of Table 4 ("Complex A+B") was prepared at concentrations of 1%, 2%, and 4% by weight in the assay buffer. The complexes A, B and A+B were each pre-incubated with MMPs and then added to the 96-well plate containing FRET peptides. A positive control (MMPs only) and a substrate control (FRET peptide only) were also prepared as test controls.

The fluorescence of each well was detected by a multi-well microplate fluorometer at Ex/Em=490 nm/520 nm. The fluorescence reading from the substrate control represented the background fluorescence reading, which was subtracted from the readings of other wells to calculate relative fluorescence units (RFU). The data was obtained over a 3.5 hour period.

The experimental results presented in FIG. 1 show that both Complex A (Table 1) and Complex B (Table 2) are powerful inhibitors of MMPs. They demonstrate nearly equivalent inhibitory capacity at the concentrations tested in the assay. When used in the combination at 1:1 ratio by weight (Complex A+B), the composition of Table 4 provides powerful MMP inhibiting effect. In fact, Complex A+B demonstrates a 47.8% increase in MMP inhibition than Complex A alone.

Example 3

Measurements of Anti-Oxidative Effects of a Composition Comprising an MMP Inhibitor and a Natural Extract Component, a Composition Comprising a TIMP Inducing Agent and a Natural Extract Component, and the Effect of a Combination Thereof in a 1:1 Ratio Using .mu.M Copper Reducing Equivalents

Antioxidative potentials of compositions according to Tables 1, 2, and 4 were also explored using .mu.M Copper Reducing Equivalents colorimetric assay. The analysis is based on the reduction of Cu.sup.2+ to Cu.sup.+ by the combined action of all the antioxidants presented in each test compositions. A chromogenic reagent, Bathocuproine (2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline) was used to selectively detect Cu.sup.+ at the absorbance of wavelength 480 to 490 nm.

The composition according to Table 1 ("Complex A"), Table 2 ("Complex B"), and Table 4 ("Complex A+B") were each prepared in a well at concentrations of 1%, 2%, and 5%, and their absorbances at 490 nm were taken individually. A Cu.sup.2+ solution was then added to each well, followed by incubation at room temperature. After 3 minutes of incubation, absorbance of each well was again taken at 490 nm, and the difference between the absorbance readings before and after the incubation was calculated.

Antioxidant capacities of the test compositions were calculated using a set of uric acid standard curves having the difference of absorbance readings as vertical axis and concentration of uric acid standards (mM) as horizontal axis. The difference in absorbance readings in each test composition was used to calculate the corresponding uric acid standard concentration (mM). Each uric acid standard concentration was converted to ".mu.M Copper Reducing Equivalents" based on the relationship 1 mM of uric acid=2189 .mu.M Cu.sup.2+ to Cu.sup.+ (copper reducing power).

As seen in FIG. 2, the results of the test using Complex A, Complex B and Complex A+B in 1%, 2%, and 5% concentrations were expressed as ".mu.M Copper Reducing Equivalents." Here, the higher the .mu.M Copper Reducing Equivalents, the greater the total antioxidant potential. FIG. 2 shows that the composition of Complex B (Table 2) and Complex A (Table 1) both demonstrate potent antioxidant activity. The antioxidant activity of these two candidates is equivalent on a weight percent basis. When Complexes A and B are combined in a 1:1 ratio (Complex A+B), the antioxidative activity is 12.6% greater than that of the theoretical combination of the two. At the use level of 2% by weight, Complex A+B provides more than twice the antioxidant activity than Complex A alone.

Example 4

Formulation Example of a Serum Composition

TABLE-US-00005 % Active in Finished INCI Name Product Glycine Soja (Soybean) Seed Extract 0.010 Acetyl Hexapeptide-20 0.030 Pyrus Malus (Apple) Fruit Extract 0.040 Cinnamomum Cassia Bark Extract 0.010 Rheum Palmatum Extract 0.010 Tremella Fuciformis (Mushroom) Extract 0.010 Eugenia Caryophyllus (Clove) Flower Extract 0.030 Camellia Sinensis Leaf Extract 0.030 Soy Amino Acids 0.030 Butylene Glycol 2.395 Glycerin 0.300 Imidazolidinyl Urea 0.004 Potassium Sorbate 0.001 Sodium Benzoate 0.005 Citric Acid 0.005 C12-20 Alkyl Glucoside 0.600 Benzoic Acid 0.200 BHA 0.002 BHT 0.007 C14-22 Alcohols 2.400 Caprylyl Glycol 0.250 Caprylyl Methicone 1.500 Carnosine 0.200 Castor Isostearate Succinate 0.500 Cetyl Dimethicone 2.000 Ethylhexylglycerin 0.150 Fragrance (Parfum) 0.250 Hexylene Glycol 0.100 Hydrogenated Starch Hydrolysate 0.540 Hydroxyphenyl Propamidobenzoic Acid 0.050 Lecithin 0.090 Maltooligosyl Glucoside 0.940 Myristyl Nicotinate 1.000 Neopentyl Glycol Diheptanoate 6.000 Palm Alcohol 0.250 Pentylene Glycol 0.975 Phenoxyethanol 0.515 Phytosteryl Canolate 0.030 Polyacrylate-13 0.750 Polyglyceryl-10 Distearate 0.700 Polyisobutene 0.375 Polymethyl Methacrylate 1.000 Polysorbate 20 0.176 Retinol 0.099 Rosa Multiflora Fruit Extract 0.005 Sodium Hyaluronate 0.010 Sodium Polyacrylate 0.100 Tetrahexyldecyl Ascorbate 0.300 Tocopheryl Acetate 0.500 Triticum Vulgare (Wheat) Germ Extract 0.500 Vegetable Oil (Olus) 0.620 Water (Aqua) 73.406 TOTAL 100.000

Example 5

Formulation Example of an Eye Cream Composition

TABLE-US-00006 % Active in Finished INCI Name Product Glycine Soja (Soybean) Seed Extract 0.010 Acetyl Hexapeptide-20 0.030 Pyrus Malus (Apple) Fruit Extract 0.040 Cinnamomum Cassia Bark Extract 0.010 Rheum Palmatum Extract 0.010 Tremella Fuciformis (Mushroom) Extract 0.010 Eugenia Caryophyllus (Clove) Flower Extract 0.030 Camellia Sinensis Leaf Extract 0.030 Soy Amino Acids 0.030 Butylene Glycol 3.780 Glycerin 0.800 Imidazolidinyl Urea 0.004 Potassium Sorbate 0.001 Sodium Benzoate 0.005 Citric Acid 0.005 Alcohol 0.140 Aloe Barbadensis Leaf Juice Powder 0.911 BHA 0.001 BHT 0.003 C12-20 Alkyl Glucoside 0.600 C14-22 Alcohols 2.400 Caprylyl Glycol 0.290 Caprylyl Methicone 2.500 Castor Isostearate Succinate 0.500 Cetyl Dimethicone 4.000 Disodium EDTA 0.024 Ethylhexylglycerin 0.125 Fragrance 0.500 Glycine Soja (Soybean) Sterols 0.500 Halidrys Siliquosa Extract 1.000 Hexylene Glycol 0.125 Hyaluronic acid 0.500 Hydrogenated Starch Hydrolysate 0.540 Lecithin 0.180 Lilium Candidum Flower Extract 0.350 Magnesium Ascorbyl Phosphate 0.080 Mallotus Japonicus Bark Extract 0.040 Maltodextrin 0.003 Maltooligosyl Glucoside 0.940 Methylparaben 0.005 Methylsilanol Hydroxyproline Aspartate 3.946 Neopentyl Glycol Diheptanoate 6.000 Palm Alcohol 0.500 PEG-40 Hydrogenated Castor Oil 1.150 Pfaffia Paniculata Root Extract 0.800 Phenoxyethanol 0.629 Phytosteryl Canolate 0.060 Piptadenia Colubrina Peel Extract 0.650 Polyacrylate-13 1.080 Polyglyceryl-10 Distearate 1.200 Polyisobutene 0.540 Polymethyl Methacrylate 1.000 Polysorbate 20 0.146 Potassium Sorbate 0.036 Ptychopetalum Olaciodes Bark/Stem Extract 0.750 Retinol 0.050 Rubus Idaeus (Raspberry) Leaf Extract 0.005 Salicylic Acid 0.012 Sodium Benzoate 0.206 Sodium Polyacrylate 0.100 Tetrahexyldecyl Ascorbate 1.000 Tetrapeptide-21 0.002 Tocopheryl Acetate 1.000 Vegetable Oil (Olus) 1.240 Water (Aqua) 56.846 TOTAL 100.000

Example 6

Formulation Example of a Skin Moisturizer Composition

TABLE-US-00007 % Active in Finished INCI Names Product Glycine Soja (Soybean) Seed Extract 0.003 Acetyl Hexapeptide-20 0.025 Pyrus Malus (Apple) Fruit Extract 0.050 Cinnamomum Cassia Bark Extract 0.003 Rheum Palmatum Extract 0.003 Tremella Fuciformis (Mushroom) Extract 0.005 Eugenia Carophyllus (Clove) Flower Extract 0.025 Camellia Sinensis (Green Tea) Leaf Extract 0.025 Soy Amino Acids 0.020 Butylene Glycol 1.911 Glycerin 3.991 Aluminum Oxide 0.228 Ascorbyl Palmitate 0.100 Benzylidene Dimethoxydimethylindanone 0.500 Bisabolol 0.099 Calcium Pantothenate 0.009 Caprylic/Capric Triglyceride 3.526 Caprylyl Glycol 0.445 Caprylyl Methicone 2.000 Carnosine 0.050 Cetyl Alcohol 1.750 Diisostearyl Dimer Dilinoleate 1.250 Dimethicone 1.500 Disodium EDTA 0.050 Dithiaoctanediol 0.020 Ethylhexylglycerin 0.250 Fragrance 0.400 Gluconic Acid 0.020 Glyceryl Acrylate/Acrylic Acid Copolymer 0.024 Glyceryl Oleate Citrate 1.038 Glyceryl Stearate 3.300 Homosalate 8.000 Hydrolyzed Oat Protein 0.123 Hydroxyphenyl Propamidobenzoic Acid 0.002 Hydroxypropyl Starch Phosphate 1.500 Isostearic Acid 0.169 Lecithin 0.189 Magnesium Ascorbyl Phosphate 0.009 Magnesium Salicylate 0.009 Octinoxate 7.500 Octisalate 5.000 Octyldodecanol 1.750 Panthenol 0.009 PEG-100 Stearate 1.800 Pentylene Glycol 0.949 Phenoxyethanol 0.555 Phopholipids 0.009 Polyglyceryl-3 Polyricinoleate 0.153 Polyhydroxystearic Acid 0.073 Polyhydroxystearic Acid 0.080 Preservatives 0.003 PVM/MA copolymer 0.013 Stearic Acid 0.132 Sutilains 0.001 Titanium Dioxide 1.840 Xanthan Gum 0.430 Zinc Gluconate 0.009 Zinc Oxide 5.075 Zinger Officinale (Ginger) Root Extract 0.001 Water (Aqua) 41.997 TOTAL 100.000

Example 7

Formulation Example of a Serum Lotion Composition

TABLE-US-00008 % Active in Finished INCI Name Product Glycine Soja (Soybean) Seed Extract 0.003 Acetyl Hexapeptide-20 0.025 Pyrus Malus (Apple) Fruit Extract 0.050 Cinnamomum Cassia Bark Extract 0.003 Rheum Palmatum Extract 0.003 Tremella Fuciformis (Mushroom) Extract 0.005 Eugenia Carophyllus (Clove) Flower Extract 0.025 Camellia Sinensis (Green Tea) Leaf Extract 0.025 Acer Saccharum (Sugar Maple) Extract 0.010 Avena Sativa (Oat) Kernel Extract 0.001 Soy Amino Acids 0.020 Butylene Glycol 7.390 Glycerin 0.425 Betaine 0.800 Caprylic/Capric Triglyceride 1.750 Caprylyl Methicone 1.000 Cetearyl Alcohol 2.800 Ceteth-10 Phosphate 0.600 Cetyl Alcohol 0.500 Citrus Aurantium Dulcis (Orange) Fruit Extract 0.010 Citrus Medica Limonum (Lemon) Fruit Extract 0.010 Dicetyl Phosphate 0.600 Ethylhexylglycerin 0.250 Fragrance 0.250 Glycolic Acid 2.800 Hydrolyzed Lupine Protein 0.100 Hydrolyzed Sclerotium Gum 0.080 Hydroxyphenyl Propamidobenzoic Acid 0.100 Lactobacillus Ferment Filtrate 4.000 Methylisothiazolinone 0.007 Octyldodecanol 1.750 Pentylene Glycol 0.950 Phenethyl Alcohol 0.065 Polyglutamic Acid 0.070 Potassium Lactate 0.220 PPG-14 Butyl Ether 5.000 PPG-2 Methyl Ether 0.039 Saccharum Officinarum (Sugar Cane) Extract 0.010 Salicylic Acid 1.000 Sucrose 0.500 Tetrahexyldecyl Ascorbate 0.100 Triethanolamine 2.079 Urea 0.475 Vaccinium Myrtillus Fruit/Leaf Extract 0.010 Water (Aqua) 63.240 Xanthan Gum 0.600 Yogurt Powder 0.250 TOTAL 100.000

Example 8

Formulation Example of a Night Cream Composition

TABLE-US-00009 % Active in Finished INCI Name Product Glycine Soja (Soybean) Seed Extract 0.007 Acetyl Hexapeptide-20 0.050 Pyrus Malus (Apple) Fruit Extract 0.100 Cinnamomum Cassia Bark Extract 0.007 Rheum Palmatum Extract 0.007 Tremella Fuciformis (Mushroom) Extract 0.010 Eugenia Carophyllus (Clove) Flower Extract 0.050 Camellia Sinensis (Green Tea) Leaf Extract 0.050 Soy Amino Acids 0.040 Butylene Glycol 7.346 Glycerin 3.409 Ascorbyl Palmitate 0.100 Behenyl Alcohol 1.000 Bisabolol 0.200 Butyrospermum Parkii (Shea Butter) Unsaponifiables 0.750 Caesalpinia Spinosa Gum 0.011 Caffeine 0.100 Calcium Pantothenate 0.030 Caprylyl Glycol 0.445 Carnosine 0.050 Cetearyl Alcohol 4.400 Cetearyl Glucoside 0.600 Cholesterol 0.100 Dicapryl Succinate 3.000 Dimethicone 1.000 Disodium EDTA 0.050 Dithiaoctanediol 0.020 Ethylhexylglycerin 0.250 Fragrance 0.200 Gluconic Acid 0.020 Glyceryl Acrylate/Acrylic Acid Copolymer 0.018 Hydrogenated Lecithin 0.500 Hydrogenated Polydecene 0.300 Hydrolyzed Caesalpinia Spinosa Gum 0.045 Hydrolyzed Oat Protein 0.410 Hydroxyphenyl Propamidobenzoic Acid 0.002 Isostearyl Neopentanoate 0.900 Magnesium Ascorbyl Phosphate 0.030 Magnesium Salicylate 0.030 Methyl Glucose Sesquistearate 0.650 Panthenol 0.030 Pentylene Glycol 2.949 Phenoxyethanol 0.555 Phopholipids 0.030 Preservatives 0.011 PVM/MA Copolymer 0.009 Sodium Acrylate/Sodium Acryloyldimethyl 0.470 Taurate Copolymer Sodium Citrate 0.100 Sodium Hyaluronate 0.008 Sorbitan Laurate 0.150 Soybean Glycerides 2.250 Squalane 1.000 Stearic Acid 0.750 Sugar 1.000 Sutilains 0.001 Trideceth-6 0.080 Water (Aqua) 63.989 Xanthan Gum 0.300 Zinc Gluconate 0.030 Zinger Officinale (Ginger) Root Extract 0.001 TOTAL 100.000

Example 9

Formulation Example of a Renewing Serum Composition

TABLE-US-00010 % Active in Finished INCI Name Product Glycine Soja (Soybean) Seed Extract 0.003 Acetyl Hexapeptide-20 0.025 Pyrus Malus (Apple) Fruit Extract 0.050 Cinnamomum Cassia Bark Extract 0.003 Rheum Palmatum Extract 0.003 Tremella Fuciformis (Mushroom) Extract 0.005 Eugenia Carophyllus (Clove) Flower Extract 0.025 Camellia Sinensis (Green Tea) Leaf Extract 0.025 Soy Amino Acids 0.020 Butylene Glycol 4.889 Glycerin 2.643 Ascorbyl Palmitate 0.100 Bifida Ferment Lysate 0.030 Bisabolol 0.199 Bis-PEG-18 Methyl Ether Dimethyl Silane 2.000 Caffeine 0.200 Calcium Pantothenate 0.030 Caprylic/Capric Triglyceride 0.150 Caprylyl Glycol 0.445 Carnosine 0.100 Cholesterol 0.100 Cyclopentasiloxane 6.000 Dimethicone 0.100 Disodium EDTA 0.100 Dithiaoctanediol 0.020 Ethylhexylglycerin 0.250 Fragrance 0.250 Gluconic Acid 0.020 Hordeum Distichon (Barley) Extract 0.300 Hydrogenated Lecithin 0.300 Hydrolyzed Oat Protein 0.410 Hydroxyethyl Acrylate/Sodium 0.620 Acryloyldimethyl Taurate Copolymer Hydroxyphenyl Propamidobenzoic Acid 0.002 Isohexadecane 0.434 Lactose 0.090 Magnesium Ascorbyl Phosphate 0.030 Magnesium Salicylate 0.030 Methyl Gluceth-20 0.750 Mica 0.500 Milk Protein 0.060 Olea Europaea (Olive) Fruit Oil 0.250 Panthenol 0.030 PEG-40 Hydrogenated Castor Oil 1.000 Pentylene Glycol 0.949 Phellodendron Amurense Bark Extract 0.100 Phenoxyethanol 0.555 Phopholipids 0.036 Polysorbate 60 0.124 Preservatives 0.003 Santalum Album (Sandalwood) Extract 0.100 Silica 1.250 Sodium Hyaluronate 0.015 Water (Aqua) 73.996 Xanthan Gum 0.250 Zinc Gluconate 0.030 Zinger Officinale (Ginger) Root Extract 0.001 TOTAL 100.000

While the present invention has been described with reference to the preferred embodiment and alternative embodiments, which have been set forth in considerable detail for the purposes of making a complete disclosure of the invention, such embodiments are merely exemplary and are not intended to be limiting or represent an exhaustive enumeration of all aspects of the invention. The scope of the invention, therefore, shall be defined solely by the following claims. Further, it will be apparent to those of skill in the art that numerous changes may be made in such details without departing from the spirit and the principles of the invention. It should be appreciated that the present invention is capable of being embodied in other forms without departing from its essential characteristics.