Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
  • A61K8/676—Ascorbic acid, i.e. vitamin C
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/42—Amides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
  • A61K8/66—Enzymes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/73—Polysaccharides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9789—Magnoliopsida [dicotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/16—Emollients or protectives, e.g. against radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/18—Antioxidants, e.g. antiradicals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
  • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/52—Stabilizers
  • A61K2800/522—Antioxidants; Radical scavengers

Definitions

• This invention concerns a topical antioxidant composition for the protection and treatment of human skin, particularly skin that is exposed to harmful ultraviolet radiation.
• the ultraviolet (UN) wavelengths of sunlight can cause sunburn (erythema) and blistering (edema). Exposure to ultraviolet light can also cause the skin to feel dry and taut in moderate doses, and to peel if exposed to higher doses.
• sunburn erythema
• blistering edema
• Exposure to ultraviolet light can also cause the skin to feel dry and taut in moderate doses, and to peel if exposed to higher doses.
• These acute, or short term, effects are readily perceptible. However, there are also more subtle acute effects that are not as readily discernable, such as photo- immunosuppression, cross-linking of deoxyribonucleic acid (D ⁇ A), formation of sunburn cells, and loss of Langerhans cells. Even more serious long term effects can occur, such as skin cancer and premature aging of the skin.
• D ⁇ A deoxyribonucleic acid
• Sunscreen products are known to protect the skin from some of the harmful effects of ultraviolet light exposure. These products contain molecules that absorb the harmful wavelengths of ultraviolet light before they can reach the skin. The absorbed light is converted to heat and rapidly dissipated to the skin and environment, which allows these molecules to revert to a lower energy state, and subsequently absorb another photon of light. In this manner, sunscreen agents can absorb numerous photons of ultraviolet light in a relatively short period of time. By absorbing the harmful wavelengths of light, sunscreen products prevent many of the acute and chronic effects caused by ultraviolet light.
• sunscreen products are not perfect in their mode of action. No single sunscreen agent is capable of absorbing all of the harmful wavelengths striking the skin.
• Higher Sun Protection Factor (SPF) formulations address this problem by including a combination of sunscreen agents in the formulation.
• the skin possesses defense mechanisms against the generation of ROS. These defenses include the presence of enzymes such as superoxide dismutase, catalase, glutathione transferase, glutathione peroxidase and glutathione reductase, as well as antioxidants such as tocopherols, ubiquinone, ubiquinol, ascorbic acid and dehydroascorbic acid.
• enzymes such as superoxide dismutase, catalase, glutathione transferase, glutathione peroxidase and glutathione reductase
• antioxidants such as tocopherols, ubiquinone, ubiquinol, ascorbic acid and dehydroascorbic acid.
• ultraviolet light entering the skin can easily overwhelm these defense systems, such that the amount of superoxide dismutase and glutathione transferase in the skin declines significantly upon irradiation with solar simulated ultraviolet light.
• SPF value The effectiveness of sunscreen products is expressed as a SPF value.
• a SPF value is recognized as the ratio of the irradiation time required to elicit a minimum erythemal reaction (sunburn) on sunscreen protected skin using a solar simulator, to the irradiation time required to elicit the same minimum erythemal reaction (sunburn) on unprotected skin.
• This test is conducted under clinical conditions according to the procedure described in the Proposed Monograph for Sunscreen Containing Drug Products (hereafter referred to as the Proposed Monograph) published by the U.S. Food and Drug Administration (FDA) in the U.S. Federal Register, Nol. 43, August 25, 1978, Part 2, pages 38206-38269, which is incorporated by reference.
• SPF Sun Protection Factor
• a waterproof product is one that exhibits its labeled SPF value after 80 minutes of exposure to water under conditions that simulate swimming for that period of time.
• a water resistant product is similarly defined, except that it must withstand 40 minutes of water exposure.
• the most common sunscreen products sold in today's market are oil-in- water emulsions incorporating stearic acid neutralized with triethanolamine.
• the SPF values of such emulsions range from 2 to 50, and they commonly include ethylhexyl methoxycinnamate as the sunscreen agent.
• padimate O can be used in place of the ethylhexyl methoxycinnamate or the salicylates mentioned above.
• Dioxybenzone, avobenzone or menthyl anthranilate can be used in place of oxybenzone. If the product does not claim to be substantive to the skin (i.e. , waterproof or water resistant), trolamine salicylate or DEA methoxycinnamate can be used in place of (or in combination with) the ethylhexyl methoxycinnamate, ethylhexyl salicylate or homosalate. Additionally, sulisobenzone may be used in such non-substantive formulations in place of oxybenzone.
• the Proposed Monograph lists 21 active ingredients that can be used individually or in combinations to achieve the desired product SPF.
• suncare products can be found in almost any desired form, such as oils, sticks, gels, ointments and pastes.
• SPF of these product forms are dependent upon the sunscreen agents employed, their concentration in the formulation, and the content as well as type and amount of any volatile components in the formulation (such as water, alcohol, and volatile oils).
• the most popular sunscreen products sold in the market today are TEA stearate based oil-in- water lotion formulations exhibiting SPFs of 15 and above. Most of the SPF 15 formulations contain approximately 7.5% ethylhexyl methoxycinnamate and 4.0% oxybenzone.
• the SPF values can be increased to a value of about 30.
• SPF values of up to 50 can be obtained.
• An emulsifier technology from Goldschmidt Chemical Company uses a silicone emulsifier which can be used to formulate water-in-oil lotion products.
• An example of this emulsifier is Abil EM 90, which is a nonvolatile silicone oil that includes cetyl dimethicone copolyol.
• Another example of this emulsifier is Abil WE 09, which is a nonvolatile silicone oil that contains polyglyceryl-4- isosterate, cetyl dimethicone copolyol and hexyl laurate.
• the chemical structures of such emulsifiers are disclosed in U.S. Patent No. 5,482,714, which is incorporated by reference, and which describes use of the emulsifier in a skin protectant emulsion.
• U.S. Patent No. 5,447,715 discloses that volatile silicone oils can be used to improve the SPF value of a non-aqueous waterproof sunscreen composition, but such a non-aqueous product would be unsuitable to formulate aqueous emulsions.
• Vitamins have been reported to have antioxidant properties. Antioxidants are materials capable of blocking the biochemical cascade of inflammatory mediators produced by free radicals. Compositions that incorporate Vitamins A or E, or their derivatives, in sunscreen compositions, are shown in U.S. Patent Nos. 4,454,112; 5,532,805; and 5,378,461. The use of Vitamin C in combination with Vitamins A, E, B and other agents in a skin protectant composition, is described in U.S. Patent No. 4,938,960.
• An antioxidant preparation that is said to protect the skin against harmful ultraviolet radiation is disclosed in U.S. Patent No. 5,607,921, and contains Vitamin C, in combination with Vitamins A and E, and monosaccharide or amide precursors.
• Sunscreen compositions containing panthenol and other agents are disclosed in U.S. Patent Nos. RE 33,845; 5,505,935; 5,445,823; and 5,573,754.
• the antioxidant effect of superoxide dismutase when externally applied to the skin to protect against the effects of ultraviolet radiation is also described in U.S. Patent No. 5,601,806.
• the present invention provides a therapeutic or cosmetic composition containing new antioxidants, or agents that reduce sun induced skin damage and inflammation by aborting the production of prostaglandins in the skin.
• the composition has a superior therapeutic or cosmetic effect. Certain embodiments provide more protection from the adverse effects of ultraviolet light, without having to include excessive concentrations of sunscreen agents in a protective formulation.
• the invention includes a composition and method for inhibiting skin damage induced by ultraviolet radiation, by applying topically to the skin an antioxidant composition which includes beta glucan or grape seed extract in a sufficient amount to protect the skin from damaging effects of ultraviolet radiation.
• the composition includes panthenol, beta blucan, grape seed extract, Vitamin C (and its analogues, such as magnesium ascorbyl phosphate, ascorbyl palmitate, etc.), and superoxide dismutase, which act synergistically to improve cellular viability and reduce the production of inflammatory prostaglandin PGE 2 in skin exposed to ultraviolet radiation.
• the composition can also include Vitamin A (retinol and its analogues, such as retinyl palmitate) and Vitamin E (tocopherol and its analogues, such as tocopheryl acetate), which also act synergistically as an antioxidant in the skin.
• Vitamin A retinol and its analogues, such as retinyl palmitate
• Vitamin E tocopherol and its analogues, such as tocopheryl acetate
• Further embodiments take advantage of the surprising finding that a mixture of one or more antioxidants and sunscreen agents in an emulsion, such as a water-in-oil (W/O) emulsion, exhibits unexpectedly superior protection of the skin against the detrimental effects caused by exposure to ultraviolet radiation.
• W/O water-in-oil
• the composition includes at least 0.005% beta glucan, 0.005% panthenol, 0.00001 % grape seed extract, 0.0001 % Vitamin C, and 0.0001 % superoxide dismutase.
• the composition may contain 0.005-5.00% beta glucan, 0.005-5.00% panthenol, 0.00001-1.00% grape seed extract, 0.0001-3.00% Vitamin C, and 0.0001-1.0000% supei oxide dismutase.
• the composition may further include at least 0.0005% Vitamin A, and at least 0.05% Vitamin E, for example 0.0005-0.50% Vitamin A, and 0.05-30.00% Vitamin E. All percent compositions are given by weight in this specification.
• the topical composition includes beta glucan and/or grape seed extract in a sufficient amount to improve cellular viability in the skin when applied topically before or after exposure to ultraviolet radiation, and at least one other skin protectant that reduces skin damage caused by ultraviolet light.
• the skin protectant may be selected from the group consisting of one or more of panthenol, grape seed extract, Vitamin C, superoxide dismutase, Vitamin A or Vitamin E in a sufficient amount to reduce production of PGE 2 , or increase cellular viability, in the skin when applied topically.
• the Vitamin C may be in the form of magnesium ascorbyl phosphate
• Vitamin A may be in the form of Vitamin A palmitate
• Vitamin E may be in the form of Vitamin E acetate.
• the invention also takes advantage of the surprising finding that a mixture of an antioxidant and a sunscreen in an emulsion, such as a water-in-oil (W/O) emulsion, exhibits unexpectedly superior protection of the skin against the detrimental effects caused by exposure to ultraviolet radiation.
• W/O water-in-oil
• the antioxidant composition is therefore a composition which comprises (or consists essentially of) the antioxidant, a sunscreen, and a sufficient amount of a non-volatile emulsifier (such as an organopolysiloxane, for example an alkylpolysiloxane, such as an alkyl dimethicone emulsifier, including a polysiloxane polyalkyl polyether copolymer) that enhances a sun protection factor (SPF) of the composition.
• the composition may comprise, for example, a low level of sunscreen agent (or agents) in combination with a mixture of antioxidants in a water-in-oil organopolysiloxane and polyglycerol fatty acid ester emulsion.
• the sunscreen includes one or more agents selected from the group of ethylhexyl methoxycinnamate, DEA methoxycinnamate, padimate O, ethylhexyl salicylate, homosalate, TEA salicylate, oxybenzone, dioxybenzone, sulisobenzone, avobenzone, octocrylene, titanium dioxide, zinc oxide or menthyl anthranilate.
• agents selected from the group of ethylhexyl methoxycinnamate, DEA methoxycinnamate, padimate O, ethylhexyl salicylate, homosalate, TEA salicylate, oxybenzone, dioxybenzone, sulisobenzone, avobenzone, octocrylene, titanium dioxide, zinc oxide or menthyl anthranilate.
• the sunscreen includes at least one UVA sunscreen agent selected from the group of oxybenzone, dioxybenzone, sulisobenzone, avobenzone or zinc oxide, and at least one UVB sunscreen agent, selected from the group of ethylhexyl methoxycinnamate, DEA methoxycinnamate, padimate O, ethylhexyl salicylate, homosalate, TEA salicylate, octocrylene or titanium dioxide.
• the sunscreen comprises at least oxybenzone and at least one of ethylhexyl methoxycinnamate and octyl salicylate.
• the antioxidant in the composition may include a mixture of one or more of the individual antioxidants described above.
• die composition is a sun-protective preparation in the form of an emulsion, wherein the composition is at least 50% water, and the emulsifier includes 1-12 % of an emulsification system that includes cetyl dimethicone copolyol, and the sunscreen agent and antioxidant are present in an amount sufficient to maintain the SPF of the composition at a value greater than about 15, or even 30 or greater.
• the sum of the SPF values of the antioxidant and sunscreen components tested separately is no more than about 70% (for example no more than 50% or 60%) of the SPF value of the sunscreen components tested together.
• the invention also includes an ultraviolet radiation protective composition, comprising about 0.0002-4% of a lipid soluble antioxidant component that includes Vitamin A and Vitamin C, about 0.004-5% of a water soluble component that includes Vitamin C, beta glucan, grape seed extract, and superoxide dismutase, and a sunscreen component that contains less than about 12% of sunscreen agents, and an emulsifier.
• the emulsifier is a polyalkylsiloxane, and may further include hexyl laurate and an ester, such as a polyglyceryl isostearate.
• the invention also includes a method of improving an SPF value of a formulation for protecting skin from the harmful effects of ultraviolet radiation, by combimng one or more antioxidants with one or more sunscreen agents, in the presence of an emulsifier, such as a water-in-oil emulsion, for example an organopolysiloxane emulsifier, sufficient to enhance the SPF value of the formulation to greater than (for example at least 10 percent, 20 percent, or even 40% more than) the sum of the SPF value of the antioxidants and sunscreen agents alone.
• the invention also includes a method of protecting skin from the effects of ultraviolet radiation, by applying the emulsion of one or more sunscreen agents and one or more antioxidants to the skin prior to exposure to ultraviolet radiation.
• composition of the present invention may be provided in many forms, such as an aqueous or non-aqueous solution, suspension or an emulsion (water-in-oil or oil-in- water).
• the composition may be a skin toner composition, a moisturizing lotion, a sunscreen composition, a skin cleanser, or any other skin treatment composition.
• the composition may also be used in methods of protecting skin against the harmful effects of ultraviolet radiation, by applying topically to the skin an amount of the composition effective to reduce the production of PGE 2 in the skin, or improve cellular viability.
• the composition may be applied before or after exposure to the sun, but is preferably applied prior to sun exposure, for example immediately before sun exposure.
• the combination of antioxidants in the present composition provides unexpectedly superior protection against the damaging effects of ultraviolet light exposure to that provided by the individual antioxidants. Furthermore, the present invention takes advantage of the surprising finding that a mixture of one or more of the antioxidants and sunscreen agents synergistically combine in a water-in-oil emulsion to provide unexpectedly superior protection to the skin against the harmful effects of ultraviolet radiation.
• a mixture of antioxidants exhibits more antioxidant activity than any of the individual antioxidant materials tested alone.
• this synergistic combination of antioxidants may be incorporated into a water-in-oil emulsion formulation that exhibits SPF values which far exceed SPF values that would be expected given the low concentration of sunscreen agents present in the formulation.
• the particular combination of antioxidants, and the low level of sunscreen agents in this water-in-oil emulsion system, are unexpectedly synergistic as measured by SPF values.
• the sunscreen agents employed in the formulations are the same combinations used in some traditional formulations, such as ethylhexyl methoxycinnamate and oxybenzone. However, the levels of these sunscreen agents are significantly lower than those of more traditional oil-in-water suncare product formulations. Additionally, the combination of antioxidants employed in the formulations covered by this technology is unique.
• the antioxidant combination includes a mixture of beta glucan, Vitamin E acetate, Vitamin A palmitate and magnesium ascorbyl phosphate (stabilized Vitamin C), panthenol, grape seed extract and superoxide dismutase. The effect that this combination of antioxidants has upon the skin, as measured by its free radical scavenging activity, and the low SPF of the emulsion when combined with sunscreen agents, is novel and unexpected.
• an “antioxidant” is a compound that reduces the inflammatory biochemical cascade initiated by reactive oxygen species.
• Antioxidants include, for example, Vitamin C and Vitamin E (and their esters), magnesium ascorbyl phosphate, panthenol, beta glucan, grape seed extract, superoxide dismutase, and mixtures of one or more of these individual antioxidant agents.
• a "non- volatile" siloxane includes an organopolysiloxane that has a flash point of at least about 200°F. Hence a cetyl dimethicone polyol, such as ABIL WE09 (which has a flash point of 255°F.) would be a nonvolatile siloxane.
• a "siloxane” is a straight chain compound (analogous to paraffin hydrocarbons) containing silicon atoms bonded to oxygen and so arranged that each silicon atom is linked with four oxygen atoms:
• a “silicone” or “polyorganosiloxane” is an organosilicon polymer containing chains of alternating oxygen and silicon atoms with substituent organic groups, frequently methyl or phenyl, attached to each silicon atom, as described for example in Remington: The Science and Practice of Pharmacy , 19 th edition, pages 867-868, and as shown below:
• the emulsifier is a non-volatile silicone oil, for example a polysiloxane polyalkyl polyether copolymer, also known as copolyols, having a molecular weight from 10,000 to 50,000, which are disclosed for example in U.S. patent No. 5,746,945, which is incorporated by reference, and
• R I ' R I " CR include:
• R' are each chosen from -H and C W8 alkyl, and R" is -
• the emulsifier can also include a dimethicone selected from alkyl- and alkoxy-dimethicone copolyols, such as those disclosed in U.S. Patent Application
• a particularly preferred copolyol is cetyl dimethicone copolyol, available from T.H. Goldschmidt as Abil
• aqueous means that the composition is not substantially free of water.
• An emulsion is a dispersed system containing at least two immiscible liquid phases.
• An emulsion in which water is the dispersed phase and oil is the dispersion medium is a "water-in-oil” emulsion.
• An “aqueous emulsion” refers to an emulsion that contains water as one of its phases.
• a “sunscreen agent” is an agent that, in an effective amount, reduces the amount of skin erythema by blocking exposure to ultraviolet radiation, as determined (for example) by the procedures set forth in the Proposed Monograph. The sunscreen agent can protect against either UV-B type ultraviolet radiation or UV-A type ultraviolet radiation, or both.
• the sunscreen agent is an aromatic compound (such as oxybenzone and cinnamic acid derivatives) which efficiently absorb harmful ultraviolet rays, and is substantially free of particulate sunscreens such as ZnO or TiO 2 , or other metal oxides that may have an adverse effect on the stability of the antioxidant agents in the composition.
• Particular embodiments of the composition also exclude copper or iron, that may also have adverse effects on stability.
• Typical suitable UV-B type sunscreening agents include substituted para- aminobenzoates , e.g., octyl dimethyl PABA, available from Van Dyk & Co., Inc. , Belleville, N.J. 07109 under the tradename Escalol 507 and usually present in the range of about 0 to 8 weight percent (for example 1.5 to 8 weight percent); alkyl esters of para-methoxycinnamate, e.g., octyl para-methoxycinnamate, available from Givaudan Corp., Clifton, N.J.
• substituted para- aminobenzoates e.g., octyl dimethyl PABA, available from Van Dyk & Co., Inc. , Belleville, N.J. 07109 under the tradename Escalol 507 and usually present in the range of about 0 to 8 weight percent (for example 1.5 to 8 weight percent); alkyl esters of para-methoxycinnamate, e.g.,
• Parasol MCX usually present in the range of about 0 to 7.5 weight percent (for example 1.5 to 7.5 weight percent); and certain esters of salicylic acid, e.g., homomenthyl salicylate, usually in the range of about 0 to 15 weight percent (for example 4 to 15 weight percenter octyl salicylate, usually in the range of about 0 to 5 weight percent (for example 3 to 5 weight percent).
• certain esters of salicylic acid e.g., homomenthyl salicylate
• octyl salicylate usually in the range of about 0 to 5 weight percent (for example 3 to 5 weight percent).
• Typical suitable UV-A type sunscreening agents include benzophenone-3 usually present in the composition in the range of about 0 to 6 percent (for example 0.5 to 6 percent) and available from American Cyanamid Co., Wayne, N.J. 07470 under the tradename Spectra-Sorb UV-9; benzophenone-8, usually present in the composition in the range of 0 to 3 weight percent (for example 0.5 to 3 weight percent) and available from American Cyanamid Co. under the tradename Spectra-Sorb UV-24; and menthyl anthranilate, usually present in the composition in the range of about 0 to 5 weight percent (for example 3.5 to 5 weight percent) and available from Haarmann and Reimer (N.J.) under the tradename Sunarome UVA.
• benzophenone-3 usually present in the composition in the range of about 0 to 6 percent (for example 0.5 to 6 percent) and available from American Cyanamid Co., Wayne, N.J. 07470 under the tradename Spectra-Sorb UV-9
• compositions of the present invention preferably contain at least one UV-B type sunscreening agent and at least one UV-A type sunscreening agent.
• compositions of the present invention may also contain perfumes, preservatives, dyes, softeners, physical reflectors and other antioxidants, as well as any other class of materials whose presence may be cosmetically or otherwise desirable.
• antioxidants include propyl, octyl and dodecyl esters of gallic acid, butylated hydroxyanisole (usually as a mixture of ortho and meta isomers), butylated hydroxy toluene and nordihydroguaiaretic acid.
• suitable preservatives include the lower alkyl esters of para-hydrobenzoates (parabens) especially, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben and mixtures thereof, and benzoic acid.
• suitable perfumes include any oil soluble perfume or fragrance or mixture of perfumes or fragrances well known to those skilled in the art.
• Typical suitable physical reflectors include talc, kaolin, chalk, precipitated silica, zinc oxide, and titanium dioxide.
• compositions of the present invention may be in the form of a liquid, gel or semi-solid.
• ingredient type and amount is dictated by the nature of the composition, i.e. gel or semi-solid, and is within the skill of cosmetic chemists. For example, larger amounts of wax are incorporated into the semi- solid compositions of the present invention than into the liquid ones.
• waterproofing effective amount of at least one waterproofing agent means that if a waterproofing agent is used , the waterproofing agent(s) is present in the composition at a concentration of at least 0.3 percent, and for example in the range 0.3 - 3 percent.
• suitable waterproofing agents include copolymers derived from polymerization of octadecene-1 and maleic anhydride, for example using procedures such as those disclosed in U.S. Patent No. 3,860,700.
• a particular waterproofing agent is a copolymer commercially available from Chevron Chemicals Co. under the tradename PA- 18 poly anhydride resin. Others include PVP/Eicosene Copolymer, PVP/Hexadecene Copolymer, and PVA/VA Copolymer, all available from GAF of Wayne, NJ.
• Typical suitable cosmetic waxes include ozokerite, lanolin alcohol, paraffin wax, bayberry wax, polyethylene wax, especially AC 617 available from Allied- Signal Corp., Morristown, N.J.; Polawax (a reaction product of higher fatty alcohols and ethylene oxide available from Croda, Inc., New York., N.Y.
• Embodiments that also include volatile silicone oils include cyclomethicones such as Dow Corning 344 Fluid, Dow Corning 345 Fluid, Dow Corning 244 Fluid, and Dow Corning 245 Fluid; as well as Volatile Silicone 7207, a trademark of Union Carbide Corp., Danbury, CT., low viscosity dimethicones, i.e. dimethicones having a viscosity of about 50 cst or less, especially dimethicones such as Dow Corning 0.5-200 cst Fluid (Midland, MI).
• cyclomethicones such as Dow Corning 344 Fluid, Dow Corning 345 Fluid, Dow Corning 244 Fluid, and Dow Corning 245 Fluid
• Volatile Silicone 7207 a trademark of Union Carbide Corp., Danbury, CT.
• low viscosity dimethicones i.e. dimethicones having a viscosity of about 50 cst or less, especially dimethicones such as Dow
• Cyclomethicone and dimethicone are names given by the Third Edition of the CTFA Cosmetic Ingredient Dictionary to cyclic dimethyl polysiloxane compounds and a mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units, respectively.
• Other volatile silicone oils having a low heat of vaporization such as those available from General Electric Co., Silicone Products Div., Waterford, NT. and SWS Silicones Div. of Stauffer Chemical Co., Adrian, MI, can also be used in the compositions of the invention.
• Typical suitable cosmetic emollients include mineral oil, especially mineral oils having a viscosity in the range of 50 to 500 SUS, lanolin oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extract, jojoba oil, safflower oil, corn oil, liquid lanolin, cottonseed oil, and peanut oil.
• Suitable cosmetic emollients include Purcellin oil, perhydrosqualene, castor oil, polybutene, odorless mineral spirits, sweet almond oil, calophyllum oil, ricin oil, vitamin E acetate, mineral spirits, the oil of cereal germs, such as the oil of wheat germ, and esters such as isopropyl palmitate, isopropyl myristate, butyl myristate, hexadecyl stearate, decyl oleate, acetyl glycerides, the octanoates and benzoates of (C12-C15) alcohols, the octanoates and decanoates of alcohols and polyalcohols such as those of glycol and glycerol, ricin oleates of alcohols and poly alcohols, such as those of isopropyl adipate, hexyl laurate and octyl dodecanoate.
• Cosmetic emollients which are solids or semi-solids at ambient temperatures may be used if admixed with one or more of the cosmetic emollients listed above, in amounts sufficient to provide liquid topical compositions.
• Such solid or semi-solid cosmetic emollients included hydrogenated lanolin, hydroxylated lanolin, acetylated lanolin, petrolatum, isopropyl lanolate, cetyl myristate, myristyl myristate, myristyl lactate, cetyl alcohol, isostearyl alcohol and isocetyl lanolate.
• EXAMPLE 1 Cellular Viability Assay This example describes how antioxidant activity was measured using a cellular viability assay.
• the antioxidant activity of individual and combinations of antioxidant materials were evaluated in cell cultures using the Epiderm Skin Model (EPI-100) from the Mattek Corporation of Ashland, MA. These cell cultures of neonatal foreskin were cultured in accordance with the manufacturer directions, and were assayed for percent cellular viability by measuring the amount of 3-(4,5- dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye taken up by the cell cultures. Viable cells take up this dye and convert it to insoluble formazin crystals that reside in the mitochondria of the cells until extracted with alcohol.
• EPI-100 Epiderm Skin Model
• MTT 3-(4,5- dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide
• the amount of MTT converted to extractable formazin crystals is directly proportional to the viability of the cell culture. MTT is measured spectrophotometrically.
• Cells exposed to UV light at a rate of 1.5 Minimal Erythemal Dose (MED) per hour per square centimeter from a solar simulator (filtered to yield wavelengths in the region of 290-400 nm) in the presence of the antioxidant ingredient or mixtures were used to measure the effect of antioxidants to protect the cell culture from the generation of free radicals.
• the total dose of ultraviolet light was 31.5 mJ/cm 2 .
• the controls for this portion of the study were cell cultures without added antioxidants (positive control). All cell cultures were also compared to cultures that were not exposed to UV light and did not include antioxidant agents or blends in order to determine percent cellular viability (negative control). This latter measurement was assumed to be equal to 100% viability. Three cell cultures were run for each antioxidant ingredient, blend or control sample tested. The results for these assays were then averaged.
• This example describes how prostaglandin production was measured using a PGE 2 assay.
• the cell cultures were evaluated for the production of Prostaglandin E 2 (PGEy using an assay kit obtained from Perspective Diagnostics of Cambridge, MA.
• the cell cultures were exposed to a dose of ultraviolet light at a rate of 1.5 MED per hour per square centimeter from a solar simulator in the presence of the antioxidant ingredients, blends or controls.
• the total dose of ultraviolet light was 31.5 mJ/cm 2 .
• These cell cultures were then allowed to stand in normal growth media for 24 hours. After being allowed to grow for that period of time, the cell cultures were assayed for production of PGE 2 using the assay kit from Perspective Diagnostics.
• the controls for this portion of the study were cell cultures exposed to the same dose of ultraviolet radiation but without added antioxidants (positive control). Three cell cultures were run for each antioxidant ingredient, blend or control sample tested. The results for these assays were then averaged.
• Blend B composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase, provides statistically superior protection to each of its individual components other than DL panthenol (data not shown). It might have been statistically superior to DL panthenol if the standard deviation of this antioxidant agent had been smaller.
• Blend A composed of Vitamin E Acetate and Vitamin A palmitate, provides statistically superior protection when compared to its constituent ingredients at the 90% confidence level.
• the level of statistical confidence is based upon hypothesis testing using a Student t test.
• Vitamin C Ascorbic Acid
• Blend A is composed of Vitamin A palmitate and Vitamin E acetate.
• Blend B is composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
• This cell culture was exposed to UV light in the absence of added antioxidant materials.
• Blends A and B provide statistically significant protection from ultraviolet light when assayed for PGE 2 .
• Production of PGE 2 resulting from ultraviolet light exposure for Blends A, B, and C is shown in Table 4.
• Blend B provides statistically superior protection from the production of PGE 2 when compared to its constituent ingredients. This statement is also valid for Blend A.
• the PGE 2 produced is also noted to be as low with grape seed extract and magnesium ascorbyl phosphate alone.
• the level of statistical confidence is based upon hypothesis testing using a Student t test.
• Vitamin C Ascorbic Acid
• Blend A is composed of Vitamin A Palmitate and Vitamin E Acetate.
• Blend B is composed of Beta Glucan, DL Panthenol, Grape Seed Extract, Magnesium Ascorbyl Phosphate and Superoxide Dismutase.
• beta glucan to interfere with the production of an inflammatory mediator (such as PGE 2 ), or to increase cellular viability following exposure to ultraviolet radiation, is also believed to be unique. Furthermore, the finding that these blends of antioxidant agents exhibit superior protection when mixed together is unexpected.
• Blend C The combination of blends A and B, which is designated as Blend C in Table 3, was shown to provide statistically significant protection against the damaging effects of ultraviolet light using skin cell cultures. A comparison of this blend of antioxidants was found to be similar to the level of protection afforded by its oil and water soluble component blends. Based upon the results shown in Tables 1 and 2, there is evidence that Blend C provides more protection than its component ingredients. The data obtained from these tests are shown in Tables 3 through 6.
• Blend A 49.0 ⁇ 4.1 Yes (95%)
• Blend B 3 42.0 ⁇ 7.4 Yes (95%)
• Blend C 4 38.2 + 1.7 Yes (95%)
• Blend A is composed of Vitamin A palmitate and Vitamin E acetate.
• Blend B is composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
• Blend C is a mixture of Blends A and B.
• Blend A 2 4380 ⁇ 545 Yes (95%)
• Blend B 3 2370 ⁇ 352 Yes (95%)
• Blend C 4 2940 + 123 Yes (95%)
• the level of statistical confidence is based upon hypothesis testing using a Student t test.
• Blend A is composed of Vitamin A palmitate and Vitamin E acetate.
• Blend B is composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
• Blend C is a mixture of Blends A and B. TABLE 5
• Blend A is composed of Vitamin A Palmitate and Vitamin E acetate.
• Blend B is composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
• Blend C is a mixture of Blends A and B.
• Blends A and B provide statistically significant protection from the damaging effects of ultraviolet light in both the Percent Cellular Viability and PGE 2 production assays.
• Blend C (which is composed of the ingredients in both Blends A and B) also showed statistically significant protection in these same tests when compared to cell cultures without the addition of the antioxidants.
• Blend A was found to provide statistically better protection than Blend C.
• Blends A and B were not found to provide statistically different levels of protection by this method nor were Blends B and C found to provide statistically different levels of protection from the damaging effects of ultraviolet light. In the previous test procedure (see Table 1) the same relationship was found for Blends A and B.
• Blend C 4 - - 95% The values listed in this table are the statistical confidence level of difference based upon hypothesis testing using a Student t test.
• Blend A is composed of Vitamin A palmitate and Vitamin E acetate.
• Blend B is composed of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
• Blend C is a mixture of Blends A and B.
• Blend A exhibits the best protection in the Percent Cellular Viability assay while Blend B exhibits the best protection in the PGE 2 Production assay may seem inconsistent. However, these two assays methods are different.
• ROS Reactive Oxygen Species
• Blend A was also found to provide statistically better protection in the Percent Cellular Viability assay method as compared to Blend C, whereas Blend C was found to be statistically superior for the PGE 2 production assay.
• Blend B provides statistically better protection than Blend C in the PGE 2 Production assay, it is not statistically different from Blend C in the Percent Cellular Viability assay.
• Blend C exhibits significant antioxidant activity in comparison to the individual ingredients tested previously.
• formulations to demonstrate the typical use of the protective skin composition of the present invention in skin care and over the counter (OTC) pharmaceutical products. These formulations are listed only as examples of the types of compositions that could be used, and are not all encompassing of the possible uses of the technology in skin care and OTC pharmaceutical products. One skilled in the art of formulation will readily envision other possible uses for this technology, and the invention is not restricted the use of the formulations listed below. All ingredients of the formulations listed below are shown in percentage by weight (% w/w).
• the following example is a general formula for liquid formulations of the composition.
• the following example is a formulation developed as a toner for the skin.
• Vitamin E Acetate 0.05- 30
• the following example is an oil-in-water formulation developed as a moisturizing lotion for the skin.
• the following example is a formulation developed as a waterproof sunscreen product for the skin.
• the following example is a general formulation for a moisturizing soap bar.
• Vitamin E Acetate 0.05 - 30 0.5
• Example 11 describes a waterproof SPF 20 formulation developed using a low level of sunscreens and the mixture of antioxidants in a water-in-oil emulsion.
• Example 11 provides examples of general ranges of ingredients, while Example 12 provides a specific formulation. In these Examples, Phases A and B represent an oil soluble phase, while Phase C is a water soluble phase.
• Example 11 Example 12
• Vitamin E Acetate 0.0001 - 2% 0.1 % Vitamin A Palmitate 0.0001 - 2% 0.05%
• Phase A The ingredients of Phase A were mixed in a container, and heated with mixing to 80 to 85°C until all the waxes melted. Then heating was discontinued, and the mixture cooled to 50 to 55°C.
• the ingredients of Phase B were also mixed in a container at room temperature until uniform, while trying to avoid entrapment of air by mixing slowly without creating a vortex. The mixture of Phase B was added to the mixture of Phase A and mixed thoroughly, again while avoiding entrapment of air.
• Phase C The ingredients of Phase C were mixed in an appropriate container, and heated with mixing to 45 to 50°C until all solid materials were completely dissolved. With slow but thorough mixing, Phase AB was added at 55 to 60°C to Phase C at 45 to 50°C. After completion of the addition, the batch was homogenized while maintaining a temperature of 45 to 50°C. After homogenization, the mixing was continued while beginning cooling to 30°C. Once at room temperature, the batch was packaged in appropriate containers.
• the formulation exhibited a waterproof SPF of greater than 17.9 on five subjects.
• Waterproof SPF 30 sunscreen This example describes a waterproof SPF 30 formulation developed using a low level of sunscreens and the mixture of antioxidants in a water-in-oil emulsion. All percentages are by weight. Phases A and B are oil soluble and Phase C is water soluble.
• Vitamin E Acetate 0.1 %
• composition was mixed in the same manner as described in Examples 11 and 12.
• Example 13 exhibited a waterproof SPF of greater than 32.1 on five subjects.
• the same formulation without the antioxidants (Vitamins A, C and E, Beta Glucan, Grape Seed Extract and Superoxide Dismutase) exhibited a waterproof SPF of 19.6 on the same 5 subjects.
• the formulation without the sunscreen agents but with antioxidants exhibited a waterproof SPF of 2.8.
• the present invention takes advantage of the surprising superiority found when combining two skin agents that protect the skin from ultraviolet radiation, one agent from a class of protectants that increases cellular viability, and the other from a class that decreases the production of PGE 2 in the skin, as measured by the assays of Example 1.
• the present invention also takes advantage of the result that a mixture of antioxidants and sunscreen agents synergistically combine in a water-in-oil emulsion to provide unexpectedly superior protection to the skin against the harmful effects of ultraviolet radiation.
• the compositions of the invention can be applied to skin both before or after exposure to ultraviolet radiation, to provide the protective effect, however application before exposure to the sun is preferred. Daily applications of the skin protectant may be used, even if exposure to the sun is not anticipated, to diminish the aging effects of ROS in the skin.
• the invention explicitly includes the mixture of antioxidants, either with or without the water-in-oil emulsion.
• reducing damage caused by exposure to ultraviolet radiation means reducing damage as measured by the assays of Example 1 (increased epidermal cellular viability) or Example 2 (reduced PGE 2 production by epidermal cells).
• Ultraviolet radiation refers to electromagnetic radiation having a wavelength shorter than the wavelengths of visible light and longer than those of x-rays.
• Skin injury refers to cellular damage as measured by decreased cellular viability or increased PGE 2 production, or both.
• An antioxidant is a substance that opposes the effects of ROS, either by scavenging or reducing
• ROS ROS, or interfering with the production of ROS.
• Possible surfactants include polyoxyethylene sorbitan esters of fatty organic acids (such as laureate, palmitate, stearate, oleate and myristate) containing various molar concentrations of ethylene oxide (commonly listed as polysorbate
• Possible humectants include sugars (such as sorbitol, glucose, etc.), glycerin (and its polymers), glycols (such as propylene glycol, butylene glycol, and polyethylene glycols of various molecular weights), hyaluronic acid (and its salts), pyrrolidone carboxylic acid (and its salts) as well as combinations of these ingredients.
• sugars such as sorbitol, glucose, etc.
• glycerin and its polymers
• glycols such as propylene glycol, butylene glycol, and polyethylene glycols of various molecular weights
• hyaluronic acid and its salts
• pyrrolidone carboxylic acid and its salts
• Possible preservatives include the parabens (such as the methyl, ethyl, propyl, isopropyl, butyl and isobutyl esters), imidazolidinyl urea, diazolidinyl urea, quaternium-15, phenylethyl alcohol, benzyl alcohol, phenoxyethanol, chlorphenesin, chlorhexidine digluconate as well as combinations of these ingredients.
• Possible sequestering agents include the various salts of ethylenediamine tetraacetic acid (sodium, potassium, amine and amino acid salts).
• Magnesium ascorbyl phosphate is a stabilized form of Vitamin C.
• Stabilized forms of Vitamin A can be used in the preferred embodiment of the invention, such as the alcohol retinol or any of its esters.
• Other forms such as
• Vitamin E is preferably used in its alcohol form (tocopherol), or any of its esters, or other stabilized forms.
• Possible O/W surfactants include the salts of fatty acids (such as sodium, potassium, amine or amino acid salts of stearic, myristic, oleic, lauric or palmitic acid), non-ionic surfactants such as the polysorbates listed above, sorbitan esters of fatty acids (such as stearates, myristates, oleates, laureates, and palmitates), glyceryl esters of fatty acids (stearate, myristate, oleate, laureate and palmitate), polyoxyethylene esters of lanolin acids, alcohols and other wool wax components, polyoxyethylene ethers of fatty alcohols (such as lauryl, cetyl, oleyl and stearyl), polyethylene glycol esters of fatty acids (such as laureate, stea
• Possible emollients include esters of fatty acids and fatty alcohols (such as octyl palmitate, octyl stearate, cetearyl stearate, etc.), silicone compounds (such as dimethicone, cyclomethicone, phenyltrimethicone, etc.), esters of organic acids and organic alcohols (C12-15 alkyl benzoate, octyl dodecanol, cetyl lactate, tridecyl trimellitate, octyldodecyl neopentanoate, etc.), fatty alcohols (cetyl alcohol, stearyl alcohol, etc.), castor oils, fractions of castor oils and dieir hydrogenated derivatives as well as combinations of these types of ingredients.
• esters of fatty acids and fatty alcohols such as octyl palmitate, octyl stearate, cetearyl stearate, etc.
• silicone compounds such
• Possible thickeners include acrylic acid polymers and their cross polymer derivatives, polyvinylpyrrolidone polymers, natural polymers (such as locus bean gum, xanthan gum, alginic acid and its salts, dextran, etc.), clays (hectorite, montmorillonite, etc.) as well as combinations of these ingredients.
• Possible water-in-oil (W/O) emulsifiers include the appropriate combinations of the oil-in-water emulsifiers listed above as well as cetyl dimethicone copolyols and other various other dimethicone copolyols in addition to combinations of these ingredients.
• Possible emollients and sunscreens include the emollients listed above, as well as any approved sunscreen agents such as dioxybenzone, homomenthyl salicylate, menthyl anthranilate, octocrylene, octyl methoxycinnamate, octyl paraaminobenzoate, octyl salicylate, oxybenzone, and trolamine salicylate, as well as combinations of these ingredients.
• Possible salts include sodium chloride, potassium chloride, lithium chloride and magnesium chloride or combinations of these ingredients.
• Possible detergents and cleansing agents include the salts of cocyl isethionate, isostearoyl lactylate salts (such as the sodium and potassium salts), tallow and tallow salts (such as sodium, potassium and ammonium salts), salts of lauryl and laureth sulfates (such as sodium, potassium and ammonium salts), betaines and sultaines (such as cocamidopropyl betaine or sultaine) and salts of fatty acids (such as sodium or potassium laureate, myristate, palmitate, stearate, oleate, behenate, linoleate and ricinoleate) as well as combinations of these ingredients.
• cocyl isethionate such as the sodium and potassium salts
• tallow and tallow salts such as sodium, potassium and ammonium salts
• salts of lauryl and laureth sulfates such as sodium, potassium and ammonium salts
• Possible buffering agents include all conventional buffering systems use in chemistry but especially lactic acid combined with a salt of lactic acid (such as sodium lactate) in appropriate ratios to maintain a given pH value.
• Possible humectants and skin conditioning agents include the humectants listed above, salts of isostearoyl lactylate (such as sodium or potassium), quaternium compounds (such as stearamidopropyl dimethylamine) and oat by-products (such as oat flour) as well as combinations of these ingredients.
• thickeners and colorants include those thickeners listed above (see footnote 8) and colorants such as titanium dioxide, iron oxides, FD&C and D&C colorants, ultramarine blue, carmine, annatto, chlorophyll and other natural or artificial colorants as well as combinations of these ingredients.

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