COSMETIC COMPOSITIONS COMPRISING EXFOLIATING ENZYMES AND USES THEREOF

Abstract: Cosmetic compositions for topical use that comprise an exfoliating enzyme for use in removal of at least a portion of the dead skin cells from the outer layer of skin, in conjunction with one or more botanicals, the delivery of which to subsurface layers and cells thereof of the skin is enhanced by the presence of the exfoliating enzyme. These compositions, including gels, lotions, and creams, are gentle, non-irritating and enhance the penetration of biological additives into the subsurface skin layers relative to currently commercially available compositions.

Description: COSMETIC COMPOSITIONS COMPRISING EXFOLIATING ENZYMES AND USES THEREOF Background of the Invention Field of the Invention The present invention relates to cosmetic compositions comprising proteolytic enzymes which remove the stratum corneum of the skin, thus enhancing the penetration of other active components, including biological components, into the underlying layers of the skin. Description of the Related Art Exfoliants are compounds which remove the dead cell layer (stratum corneum) of the skin, and are used, for example, in the treatment of aging skin (removal of wrinkles), photodamaged skin, acne, dry skin, and other skin conditions. Currently commercially available cosmetic formulations for topical use typically include the following exfoliants: alpha hydroxy acids (AHAs) (e.g. glycolic acid and lactic acid), beta hydroxy acids (BHAs) and retinoids, which may cause adverse reactions including skin irritation, erythema, blistering, particularly in individuals with sun damaged skin, and chronic or unusually high photosensitivity, especially among ethnic groups having darker skin tones. Thus, there is a need for cosmetic preparations comprising exfoliants which are effective and non-irritating, especially in individuals with sun damaged skin. The present invention addresses this need. Summary of the Invention Preformed embodiments of the present invention provide compositions for topical use, including but not limited to lotions, gels and creams, comprising an enzyme in combination with at least one, at least two, at least three or more, biological additive. Said enzyme is preferably papain, derivable from papaya, and is capable of removing the stratum corneum when applied thereto. The biological additives are preferably selected from the group consisting of Echinacea angustifolia extract, mimosa teπuiflora extract, hydrocotyl (centella asiatica) extract, gingko biloba extract, tea tree oil, Matricaria chamomila (chamomiie) extract, Hypericum perforatum extract, and Aloe barbedensis extract, caterndiele extract, but may be any biologically-active biologic. The pH of the compositions described herein are preferably greater than about 4.5 or, more preferably, greater than 5.0, and are most preferably about 7.0. Also described is a method for enhancing penetration of at least one, two three, or more biological additive into the skin, comprising applying to said skin a formulation comprising said at least one biological additive and an enzyme capable of removing at least a portion of the stratum corneum. The enzyme is preferably papain, is more preferably papain linked to a high molecular weight polymer, and is preferably papain linked to high molecular weight poiyacrylic acid. Also provided is a method for treating an individual having skin exhibiting at least one condition selected from the group consisting of aging skin, photodamaged skin, acne, and dry si:::'. ..'. rising: diagnosing a individual having said skin, applying to said skin a formulation comprising said at least c ~ Aical additive and an enzyme capable of removing at least a portion of the stratum corneum. Detailed Description of the Preferred Embodiment Preferred embodiments of the present invention provide effective, non-irritating topical cosmetic formulations comprising an enzyme which promotes removal of at least a portion of the stratum corneum of skin and therefore promotes deeper penetration of other compounds contained within the composition into subsurface skin. Thus, such an enzyme acts as an exfoliant, removing only portions of the dead cell layer of the skin, causing no damage to the underlying living cell layers. Currently available exfoliants, including AHAs, BHAs and retmoids tend to cause adverse topical reactions including but not limited to skin irritation, erythema and blistering. The topical enzymatic compositions disclosed herein have a pH that is more basic than the pH of skin, and preferably have a pH of about 7.0, thus contributing to their πon-irntatiπg properties relative to currently commercially available exfoliants. One preferred enzyme is papain, an enzyme obtained from unripe papaya. One particularly preferred form of papain is Linked Papain™ (papain carbomer, as described in CTFA, the International Cosmetic Ingredients Dictionary) in which papain is covalently immobilized to 1 % polyacrγlic acid (900,000 daltons), commercially available from Collaborative Laboratories, 3 Technology Drive, East Setauket, NY 11733). In a preferred embodiment, the enzyme is present in the formulation in an amount between about 1 % and 6%, more preferably between about 2% and 5%, most preferably about 4% by weight. The ability of papain to act as an exfoliant allows enhancement of penetration of any desired medicinal agent beneficial to the skin, such as, for example, biological additives [e.g., botanicals and herbals) and moisturizers. The activity of papain is greatest at a pH of 6, although the enzyme retains about 75% of its activity between pH 5 and 7. The cosmetic compositions preferably have a pH that is basic relative to the pH of skin (the pH of which typically ranging from approximately 4.5 to approximately 5.0), and preferably have a pH of about 7.0. The papain compositions described herein may be formulated for topical application with pharmaceutically acceptable carriers using methods well known in the cosmetic and pharmaceutical arts, including gels, creams, ointments, emulsions, dispersions, salves, pastes, lotions and the like. These formulations may additionally comprise one or more emulsifiers, hu ectants [e.g., glycerin or glycerol, sorbitol, and the other known polyols), skin conditioning agents (e.g., propylene glycol, sweet almond oil, apricot kernel oil), surfactants (e.g. ceteth-20), colorants such as staining dyes and pigments (e.g., calcium, barium and aluminum lakes, iron oxides, titanium dioxide and mica), antioxidants (i.e., ascorbic acid, tocopherols, ascorbyl palmitate, thiodipropiomc acid), viscosity-enhancing agents (e.g., cetearyl alcohol, polyethylene glycol), vitamins, minerals, emollients, skin conditioning agents, biological additives (e.g. botanicals or herbals), sunscreens (e.g. octyl methoxycmnamate, butyl methoxydibenzolylmethane, oxybenzone), pH adjusters, solvents, germicides (e.g., antibiotics, Tπcolsan), preservatives (e.g., BHT, methylparaben, ethylparaben, propγlparaben, butylparaben) and fragrances (e.g., strawberry extract, mangifera indica). It will be appreciated by those of skill in the art that particular compounds may be properly classified in one, or two or more of the above-listed classifications of compound types. The compositions may also include one or more biological additives, such as botanicals or herbals. As used herein, the term "biological additive" indicates any compound obtained from a natural source, including plants, animals, bacteria and yeast, which has a medicinal or otherwise beneficial effect when topically applied to the skin. Examples of biological additives include oil of Melaleuca alternifolia, oil of Lavandula angustifolia, Caπca papaya extract, Echtnacεa angustifolia extract. Mimosa tenuiflora extract, Hydrocotyl (centella) asiatwa extract, gingko biloba extract, oil of Melaleuca alternifolia (tea tree oil), Matricana chamomila (chamomile) extract, Hypeπcum perforatum extract, Aloe barbedensis extract, and the like. The biological sources for "biological additive" may also include, but are not limited to the following: Aloe Vera, Aloe Barbedensis; Arnica, Arnica Montana; Bladderwrack (seaweed), Fucus Vescicuiosis; Birch, Betula Alba (Pendula); Chamomile, Matricana Chamomila (Chamomila Recutita); Marsh Mallow, Althea Officinalis; Meadow Sweet, Spirea Uimaπa (Filipendula); Mint/Lemon Balm, Melissa Officinalis; Mimosa, Mimosa Tenuiflora; Myrrh Tincture, Commiphor Myrrha; Neem, Melia Azadirachta; Nettle (stinging), Urtica Dioica; Papaya, Carica Papaya; Propolis (bee glue), Propolis Cera; Raspberry, Rubis Idaeus; Red Poppy, Papaver Rhoeas; Rose Hip (dog rose), Rosa Canma; Rosemary, Rosemannus Officinalis; Sage, Salvia Officinalis; St. Johns Wort, Hypeπcum Perforatum; Strawberry, Fragaπa Vesca; Thea Sinensis (green tea), Camelia Sinensis; Walnut, Juglans Regia; Witchhazel (dist/extr), Hamamelis Virgimana; Yarrow, Achillea Millefolium; Wild Yam, Dioscorea Villosa; Hawthorn, Crataegus Monogma/Oxyantha; Herma (black/rod), Lawsoma Ehemus; Hops, Humulus Lupulus; Horse Chestnut, Aesculus Hippocastanum; Horse Tail, Equisitum Arvense; Ivy, Hedera Helix; Linden/Lime Tree Blossoms, Tilia Argentea Cordata; Madder, Rubia Tinctorum; Mangold, Calendula Officinalis; Centella Asiatica, Centella Asiatica Urban (hydrocotyl Asiatica); Carrot (roots), Daucus Carota; Comfrey (Allantoine), Sγmphγtum Officmale; Coneflower (Echinacea), Echinacea Angustifolia; Cucumber, Cucumis Sativus (Frucus Cucumis); Fenugreek, Tπgonella Foeπum Greacum; Gingko, Gingko Biloba; Ginseng, Panax Ginseng; Great Burdock, Radix Bardanea/Arctium Lappa; Tea Tree Oil, Oil of Melaleuca Alternifolia; Colts Foot, Tussilago Farfara; Clover, Trifolium Pratense; Speedwell, Veronica Officinalis. Further biological additives, along with the biological or medicinal properties of the biological additives described herein and of other known biological additives are know to those of skill in the art. References, including encyclopedias and treatises, known to those of skill in the art, that described such biological additives, along with the biological or medicinal properties of the biological additives described herein, include: Guenther - The Essential Oils, Van Nostrand; Int. Cosmetic Ingredient Dictionary, Vol 1 & 2, C.T.F.A. 1995; Int. Cosmetic Ingredient Handbook, C.T.F.A. 1995; British Herbal Pharmacopoeia, British Herbal Medicine Assoc, 1983; Clinical Applications of Ayurvedic & Chinese Herbs, K. Bone, Phytotherapγ Press, 1996; A Handbook of Chinese Healing Herbs, D Reed, Shambala, Boston, 1995; Echinacea - Nature's Immune Enhancer, S. Foster, Healing Arts Press, Rochester, 1991; Encyclopedia of Herbs, D. Brown, RD Press, 1995; Encyclopedia of Medicinal Plants, A. Chevalier, Dorling Kingers Ley, 1996; L'Angelica - Herbal Extracts; Cosmetochem - Herbasol Extracts. Emulsifiers contemplated for use include but are not limited to monoacyl glycerol, such as glyceryl onoalkanoates, glyceryl monoalkenoates, diacyl 1 ,2 or 1 ,3 disubstituted) glycerol, such as glyceryl dialkanoates, glyceryl dialkeπoates, polyglyceryl esters, steaπc acid, cetyl alcohol, and sorbitan stearate. Other examples of biological additives include, but are not limited to, Carica papaya extract, Echinacea angustifolia extract, tea tree oil, Mimosa tenuiflora extract, Hydrocotyl (centella asiatic) extract, gingko biloba extract, Matricana chamomila (chamomile) extract, Hγpericum perforatum extract, Aloe barbedensis extract, and the like. A particularly preferred biological additive is tea tree oil. In a preferred embodiment, one or more biological additives is present in the formulation in a combined amount of from about 1 % to 10% by weight, more preferably from about 2% to 8% by weight, and most preferably from about 4% to 6% by weight. In a preferred embodiment, one or more skin conditioning agent(s) is present in the formulation in a combined amount of from about 1 % to 20% by weight, more preferably from about 5% to 10% by weight, and most preferably from about 6% to 9 % by weight. In another preferred embodiment, one or more emollients or humectants is present in the formulation in a combined amount of from about 1 % to 10% by weight, more preferably about 2% to 8% by weight. One or more viscosity increasing agents may be present in the formulations in an amount from about 2% to 10% by weight, preferably about 5% by weight. One or more aπtioxidants may also be present in a combined amount of between about 0.1 % and 5% by weight, preferably between about 0.5% and 2% by weight. In another preferred embodiment, one or more emulsifying agents is present in a combined amount of between about 1 % and 20% by weight, more preferably between about 5% and 10% by weight. In another preferred embodiment, one or more aπtioxidants, preservatives and fragrances is present in the compositions in minor amounts, preferably between about 0.05% and 5% by weight, more preferably between about 0.1% and 2% by weight. Preferably, the compositions and formulations are directly applied to the skin once per week, once per day, twice per day or three times per day. Alternatively, the compositions and formulations may be applied directly to the skin less frequently or only on specific occasions, for example after a sunburn when the skin is peeling, to achieve certain of the benefits described herein The quantity and extent of application will vary with the particular result desired or condition to be treated. Such preferred application will vary from about 1 mg per cm 2 skin per day to 50 mg per cm 2 skin per day, massaged into the skin, as will be appreciated by those of skill in the art, depending on the severity and the condition to be treated. EXAMPLES The following three examples are illustrative, but not limiting, of topical papain formulations. EXAMPLE 1 A preferred moisturizing formulation contains: PAPAIN CONTAINING MOISTURIZER EXAMPLE 2 A preferred cream formulation of the present invention was prepared in the following manner: (1 ) Cetyl and/or myπstyl alcohol, stearic acid, polysorbate-60, sorbitan stearate, safflower (or sunflower) oil, jojoba oil, α tocopherol, sweet almond oil and octylmethoxγcinnamate were combined and melted at a temperature not exceeding 70°C until homogeneous. (2) When molten, but not overheated, half of the deionized water (at approximately 70°C) was added while mixing, resulting in formation of an emulsion. (3) The remaining deionized water (cold) was then added. (4) The emulsion was cooled to 40°C, followed by addition of propylene glycol, carica papaya extract, tilia cordata extract, Echinacea angistif olia extract, Mimosa tenuiflora extract, Centella (hydrocotyl) extract, aloe barbedensis (decolorized) extract, Matricana chamomila extract, and Hypeπcum perforatum extract. (5) The emulsion was cooled to 35°C, followed by addition of octhilinone, parabens, papain carbomer and mangifera indica. If necessary, the emulsion is homogenized. EXAMPLE 3 A preferred lotion formulation contains: PAPAIN-CONTAINING LOTION EXAMPLE 4 A preferred lotion formulation of the present invention was prepared in the following manner: Cetyl or mynstyl alcohol, stearic acid, polysorbate 60, sorbitan stearate, paraffin liquid and α tocopherol were combined and melted at 70°C until homogeneous. Half of the water was added hot (70°C) and the mixture was mixed thoroughly, followed by addition of the remainder of the water (cold through room temperature; approximately 15°C - 18°C). The mixture was cooled to 40°C, followed by addition of propylene glycol, tilia cordata extract, Echinacea angustifolia extract, aloe barbedensis distilled extract (aloe vera clear), Matricana chamomila extract, Calendula officinalis extract, Centella (hydrocotyl) asiatica extract, Hypencum perforatum extract. All extracts were diluted 1 :5 in either propylene glycol or butylene glycol. When the mixture had cooled to 30-35°C, octhilinone, methyl/ethyl/propyl/butyl parabens, colorants (to shade), mangifera indica and papain carbomer were added. If necessary, the mixture is homogenized. EXAMPLE 5 A preferred gel formulation contain: Papain-coπtaininq gel EXAMPLE 6 A preferred gel formulation of the present invention was prepared in the following manner: Carbomer was added to cold deionized water while mixing. When dispersed, propylene glycol, carica papaya extract, betula alba extract, cucumis sativus extract, panax ginseng extract, aesculus hippocastanum extract, tilia argentea extract and propolis cera extract were added. These ingredients were mixed well, followed by addition of papain carbomer (1-4%) and octhilinone, and thorough mixing. Deionized water and tπethanolamine were then added slowly (to prevent introduction of air) to form the clear gel. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications, particularly with regard to specific exemplary components and to the specific ranges of the components of the formulation, may be made thereto without departing from the spirit and scope of protection afforded the present invention described, and claimed, herein.

Claims: WHAT IS CLAIMED IS: 1. A composition for topical use comprising the enzyme papain in combination with at least one biological additive, wherein said enzyme is capable of removing the stratum corneum when applied thereto. 2. The composition of Claim 1, wherein said enzyme is present at about 2% to about 4%, by weight. 3. The composition of Claim 2, wherein said papain is linked to a high molecular weight polymer. 4. The composition of Claim 3, wherein said high molecular weight polymer is polyacrγ c acid. 5. The composition of Claim 1, wherein said biological additive is selected from the group consisting of Echinacea angustifolia extract, mimosa tenuiflora extract, hydrocotyl (centella asiatic) extract, gingko biloba extract, tea tree oil, Matricana chamomila (chamomile) extract, Hypencum perforatum extract, Aloe barbedensis extract and tea tree oil. 6. The composition of Claim 1, wherein the pH of said composition is greater than about 4.5. 7. The composition of Claim 1, wherein the pH of said composition is about 7.0. 8. A method for enhancing penetration of at least one biological additive into the skin, comprising applying to said skm a formulation comprising said at least one biological additive and an enzyme capable of removing at least a portion of the stratum corneum. 9. The method of Claim 8, wherein said enzyme is papain. 10. The method of Claim 9, wherein said papain is linked to a high molecular weight polymer. 11. The method of Claim 10, wherein said high molecular weight polymer is polyacry c acid. 12. The method of Claim 8, wherein the method enhances the penetration of at least two biological additives into the skin. 13. The method of Claim 8, wherein the method enhances the penetration of at least three biological additives into the skin. 14. A method for preparing a medicament for treating an individual having skin exhibiting at least one condition selected from the group consisting of aging skin, photodamaged skin, acne, and dry skin, comprising: combining a formulation comprising said at least one biological additive, an enzyme capable of removing at least a portion of the stratum corneum, and a suitable carrier or diluent. 15. The method of Claim 14, wherein said enzyme is papain. 16. The method of Claim 15, wherein said papain is linked to a high molecular weight polymer. 17. The method of Claim 16, wherein said high molecular weight polymer is polyacryhc acid. 18. The method of Claim 14, wherein the condition is aging skin. 19. The method of Claim 14, wherein the condition is photodamaged skin 20. The method of Claim 14, wherein the condition is acne. 21. The method of Claim 14, wherein the condition is dry skin.

Inventors: VROMEN JACOB, VROMEN, JACOB
Applicants: AUSTRALIAN IMP ERS LTD, AUSTRALIAN IMPORTERS, LTD.
Application year: 2001
Main classification: A61K6
IPC codes: A61K8, A61K36, A61Q19