WO1991007168A1 - Riboflavine comme promoteur du tannage - Google Patents

Riboflavine comme promoteur du tannage Download PDF

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Publication number
WO1991007168A1
WO1991007168A1 PCT/US1990/006328 US9006328W WO9107168A1 WO 1991007168 A1 WO1991007168 A1 WO 1991007168A1 US 9006328 W US9006328 W US 9006328W WO 9107168 A1 WO9107168 A1 WO 9107168A1
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composition
glycerol
riboflavin
agents
cis
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PCT/US1990/006328
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English (en)
Inventor
Patricia A. Agin
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Schering-Plough Healthcare Products, Inc.
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Publication of WO1991007168A1 publication Critical patent/WO1991007168A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • 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
    • A61K8/673—Vitamin B group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/04—Preparations for care of the skin for chemically tanning the skin

Definitions

  • This invention relates to the enhancement of melanin production by the topical application to the skin of Riboflavin.
  • Melanin pigmentation is largely responsible for normal skin color and protection against ultraviolet damage, including photocarcinogenesis.
  • Melanin is produced in melanocytes, neural crest derived cells situated in the basal layer of the epidermis, and is transferred via dendrites to surrounding keratinocytes, the most abundant cell in the epidermis.
  • Gordon et al. disclose that this anatomical relationship, termed the epidermal melanin unit, is envisioned as one melanocyte in contact with an estimated 36 keratinocytes in the basal and suprabasal layers.
  • IT may persist for 36-48 hours after prolonged exposure, at which stage it blends with delayed tanning (DT). See Regan, editor, The Science of Photomedicine. pp. 241-242, 1982.
  • IT occurs within minutes of exposure to UVA (320-400 nm) and to visible light.
  • Fitzpatrick et al. disclose that IT becomes most prominent within 1 hour of exposure and almost completely disappears within 4 hours.
  • Fitzpatrick et al. further disclose that studies with electron spin resonance have shown that IT reaction is probably an oxidation reaction that involves the generation of unstable semi-quinone- like free radicals in melanin.
  • DCF dopachrome conversion factor
  • ICF 5,6-dihydroxyindole conversion factor
  • Duggan et al. further disclose that these products contain tyrosine, tyrosine derivatives, tyrosine/riboflavint-complex and/or amino acid blends.
  • tyrosine is used to increase the substrate available for tyrosinase, and tyrosine was complexed with riboflavin in order to accelerate tyrosine's oxidation. See Duggan, M., et al., "Tyrosinase...The Enzyme Behind the Tan", Cosmetics & Toiletries, pp. 97-101 , March 1987.
  • the absorbed riboflavin enhances, potentiates or increases the growth and replication of melanin precursors (such as tyrosinase, melanosomal proteins, and melanoprotein) upon exposure to UV radiation (UVA 320-400 nm and/or UVB 290-320 nm) through interaction with the cell membrane and/or nuclear membranes.
  • melanin precursors such as tyrosinase, melanosomal proteins, and melanoprotein
  • this invention provides a method of enhancing melanin production comprising applying topically to the skin an effective amount of a vitamin selected from the group consisting of riboflavin, riboflavin phosphate and mixtures thereof.
  • a vitamin selected from the group consisting of riboflavin, riboflavin phosphate and mixtures thereof.
  • the riboflavin, riboflavin phosphate or mixtures thereof is applied in amounts effective to stimulate the enhanced production of melanin.
  • the riboflavin, riboflavin phosphate or mixtures thereof is combined with suitable solvents and other optional ingredients and applied as a composition.
  • Another embodiment of this invention provides a topical composition for enhancing melanin production comprising an affective amount of riboflavin, riboflavin phosphate or mixtures thereof.
  • the topical composition may optionally contain effective amounts of protein kinase C (PK-C) activators, DOPA phosphates and/or sunscreening agents.
  • PKI protein kinase C
  • compositions comprising: (a) riboflavin, riboflavin phosphate or mixtures thereof present in an amount effective to enhance melanin production when said composition is applied topically to the skin, and
  • PK-C activators optionally, at least one ingredient selected from the group consisting of: PK-C activators, DOPA phosphates, sunscreening agents, emollients, emulsifiers, solvents for sunscreening agents, solvents for said PK-C activators, waxes, thickeners, film formers, antioxidants, preservatives, surfactants, perfumes, biological additives, buffering agents, chelating agents, emulsion stabilizers, opacifying agents, pH adjusters, propellants, and coloring agents.
  • PK-C Activators are added to the compositions, an antioxidant is used.
  • the riboflavin, riboflavin phosphate or mixtures thereof are in a concentration which is effective to provide the desired level of activity.
  • the riboflavin, riboflavin phosphate or mixtures thereof are present in an amount of at least about 0.05 percent by weight of the total composition.
  • the riboflavin, riboflavin phosphate or mixtures thereof are present in an amount of about 0.1% to about 2% by weight of the total composition with about 0.1 % to about 0.3% being preferred and about 0.15% to about 0.3% being most preferred and about 0.2% to about 0.3% being even more preferred.
  • the composition is applied in a sufficient amount to uniformly coat the skin.
  • the composition is applied in an amount sufficient to provide about 0.01 mg to about 0.08 mg riboflavin, riboflavin phosphate or mixture thereof to an area of skin about 10 to about 12 cm 2 , with about 0.01 mg to about 0.06 mg riboflavin, riboflavin phosphate or mixture thereof being preferred and about 0.02 mg to about 0.05 mg being most preferred.
  • the riboflavin, riboflavin phosphate or mixture thereof composition is applied at least 1 to about 6 times with about 1 to about 3 times being preferred over a time period of about 24 hours.
  • the riboflavin, riboflavin phosphate or mixtures thereof may be combined with (such as by mixing, blending or dissolving) a known formulation (vehicle) for a sunscreening agent.
  • a known formulation for a sunscreening agent.
  • the inclusion of the sunscreening agent would be optional.
  • such a formulation contains effective amounts of water and humectant.
  • compositions of this invention may also be formed by combining the riboflavin, riboflavin phosphate or mixtures thereof with effective- amounts of water and a humectant.
  • These compositions ' are predominantly water with enough humectant added to form a cosolvent mixture that will dissolve the riboflavin, riboflavin phosphate or mixtures thereof.
  • the humectant is present in amounts of about 1 to about 7% by weight of the total composition with about 4 to about 5% being preferred.
  • the balance of the composition is water such that the total amount of ingredients (water, humectant, and riboflavin, riboflavin phosphate or mixture thereof) equals 100% by weight.
  • compositions may contain water in amounts of about 91 to about 98.95% by weight of the total compositions with about 91 to about 98.9% being suitable.
  • These compositions may conveniently contain one or more of the above mentioned optional ingredients.
  • the compositions with the optional ingredients can contain water in an amount of about 40 to about 86% by weight of the total composition, a humectant in amounts of about 1 to about 7% by weight of the total composition with about 4 to about 5% being preferred, with the balance of ingredients being selected from amongst the optional ingredients such that the total amount of ingredients (components) equals 100% by weight.
  • the composition may be formulated by combining all the ingredients except for enough water (e.g., 5% by weight of the total composition) to make a slurry of the riboflavin, riboflavin phosphate or mixtures thereof, then the slurry is added into the composition.
  • enough water e.g., 5% by weight of the total composition
  • Humectants well known in the art may be used. Examples of humectants include propylene glycol, sorbitol, and glycerin. Other suitable humectants may include fructose, glucose, glutamic acid, honey, maltitol, methyl gluceth-10, methyl gluceth-20, sodium lactate, sucrose, and the like.
  • Liposomes may also prove useful to encapsulate the riboflavin, riboflavin phosphate or mixtures thereof.
  • Liposomes are aqueous compartments enclosed by a Iipid bilayer. They are produced by techniques well known to those skilled in the art.
  • iiposomes can be produced by suspending a suitable Iipid, such as phosphatidyl choline, in an aqueous medium. This mixture is then sonicated to give a dispersion of closed vesicles that are quite uniform in size. See, for example, Stryer, Biochemistry. Third Edition, pp. 290-292, ⁇ 1988, the disclosure of which is incorporated herein by reference thereto.
  • Among the useful liposomes are stratum corneum Iipid liposomes formed from epidermal ceramide ⁇ , cholesterol, palmitic acid and cholesterol sulfate as described in Abraham et al., The Journal of Investigative Dermatology, 9_0_, 259-262 (1988) .
  • Liposome Kit is available from Sigma Chemical Company, St. Louis, Missouri under catalog number L-4262.
  • Liposome Kit L- 4262 contains L-alpha-phosphatidylcholine (egg yolk), dicetyl phosphate and cholesterol. It is a negatively charged lipsome mixture, another suitable negatively charged liposome mixture available from Sigma Chemcial Company is L-4012 which contains L-alpha-phosphatidylcholine, dicetyl phosphate and cholesterol.
  • Suitable positively charged liposome mixtures available from Sigma Chemical Company contains L-alpha- phosphatidylcholine, stearylamine and cholesterol (catalog numbers L-4137 and L-3887). Categories of Iipids in suitable liposomes are phospholipids, glycosphingolipids, ceramides, cholesterol sulfate and neutral Iipids. Various combinations of these Iipids are found in neonatal mouse, pig and human stratum granulosum and stratum corneum.
  • Iipids which can be used to make the liposomes are straight chain fatty acids, glycerol esters, glycerides, phosphoglycerides, sphingolipids, waxes, terpenes and steroids.
  • Specific preferred Iipids suitable for use are phosphatidyl choline, dicetyl phosphate and cholesterol.
  • the riboflavin, riboflavin phosphate or mixtures thereof can be encapsulated in (or trapped in) the compartment portion of the liposome by adding a solution of riboflavin, riboflavin phosphate or mixtures thereof and cosolvent mixture to a suitable Iipid and mixing (--e.g., sonicating) to produce the liposomes containing the riboflavin, riboflavin phosphate or mixtures thereof.
  • the liposome can then be combined with a suitable topical vehicle, e.g. a lotion, gel or cream vehicle.
  • a suitable topical vehicle e.g. a lotion, gel or cream vehicle.
  • the Iipid mixture which forms the liposome can be any of the conventional mixtures available or discussed in the literature- which are pharmaceutically and cosmetically acceptable.
  • Preferred Iipid mixtures contain a phosphatidyl choline, dicetyl phosphate and cholesterol.
  • the Iipid mixtures which form the liposomes are commercially available in a solvent such as ethanol or chloroform.
  • a typical mixture contains on a weight basis, seven parts phosphatidylchoiine, 2 parts dicetyl phosphate and one part cholesterol.
  • the compositions of this invention can contain a penetration enhancer to enhance the absorption of the riboflavin, riboflavin phosphate or mixtures thereof into the skin.
  • the enhancer can be used in amounts of about 0.5% to about 99% by weight of the total composition, with about 1% to about 25% being preferred and about 2% to about 10% being most preferred.
  • penetration enhancers include, but are not limited to: DMSO (dimethyl sulfoxide), Azone (laurocapram, 1-dodecylazacycloheptan-2-one, from Nelson Research, Irving, CA), N-methylpyrrolidone, alcohols such as panthenol, the SD alcohols and oleic alcohol, fatty acids such as oleic acid and linoleic acid, liposomes, and the like.
  • compositions of this invention can contain, as stated above, PK-C activators, DOPA phosphates (such as a mixture of monophosphorylated isomers of DOPA --see U.S. Patent No. 4,508,706, the disclosure of which is incorporated herein by reference thereto) sunscreening agents, emollients, emulsifiers, solvents for sunscreening agents, waxes, thickeners, film formers, humectants, antioxidants, preservatives, surfactants, perfumes, biological additives, buffering agents, chelating agents, emulsion stabilizers, opacifying agents, pH adjusters, propellants, coloring agents, and the like.
  • DOPA phosphates such as a mixture of monophosphorylated isomers of DOPA --see U.S. Patent No. 4,508,706, the disclosure of which is incorporated herein by reference thereto
  • sunscreening agents emollients, emulsifiers, solvents for sunscreening agents, waxes,
  • compositions can be formed into formulations, such as lotions, creams, gels, aerosols, and sticks, in accordance with procedures well known in the art.
  • the PK-C Activators useful in this invention are those Activators which are physiologically compatible with the skin, are readily absorbable through or into the skin, and penetrate .through the stratum corneum and the epidermis to reach the melanocytes.
  • the PK-C Activators may be used individually or in combination.
  • Suitable PK-C Activators are those physiologically acceptable substances which activate protein kinase C by their direct action, or are substances which are metabolized to other substances which activate protein kinase C, or are substances which act upon other substances to produce a resulitng substance that activates protein kinase C and may include substances selected from the group consisting of: diacylglycerols; triacylglycerols; lipopolysaccharides; unsaturated free fatty acids; short chain saturated free fatty acids; glycophospholipids; enzymes which hydrolyze glycophospholipids (phosphoglycerides) to diacylglycerols such as Phosphoiipase C which hydrolyzes the phosphodiester bond linking the phosphorylated inositol unit to the acylated glycerol moiety to form diacylglycerol in the phosphoinositide cascade; and naturally occurring substances such as bryostatins which are naturally occurring macrocylic lactone
  • the acyl groups of the diacylglycerols and triacylglycerols can be unsaturated, saturated or a combination of unsaturated and saturated.
  • Each acyl chain (group) contains at least 1 carbon atom (including the carbonyl carbon) and usually contains from about 1 to about 30 carbon atoms (including the carbonyl carbon) with about 2 to about 24 carbon atoms being preferred and about 6 to about 20 carbon atoms being most preferred.
  • the acyl group is derived from a naturally occurring fatty acid and the fatty acid usually contains an even number of carbon atoms and is unbranched.
  • the diacylglycerols are preferably 1 ,2- diacylglycerols, and most preferably 1 ,2-diacyl-sn-glycols.
  • saturated free fatty acids (fatty acids) from which the acyl groups may be derived from include, but are not limited to: methanoic (formic); ethanoic (acetic); propanoic (propionic); butanoic (butyric); pentanoic (valeric); hexanoic (caproic); heptanoic (enanthic); octanoic (caprylic); nonanoic (pelargonic); decanoic (capric); undecanoic (undecylic); dodecanoic (lauric); tridecanoic (tridecylic); tetradecanoic (myristic); pentadecanoic (pentadecylic); hexadecanoic
  • Preferred saturated acyl groups are derived from fatty acids selected from the group consisting of: acetic, hexanoic, octanoic, decanoic, hexadecanoic, octadecanoic, and eicosanoic. Most preferred saturated fatty acids are selected from the group consisting of: acetic, hexanoic, octanoic and octadecanoic.
  • Representative unsaturated free fatty acids (fatty acids) from which the acyl groups may be derived from include, but are not limited to: 1 . 10-undecenoic (10-undecyienic);
  • trans-1 1 -octadecenoic (trans-vaccenic) ; 1 1 . cis-12-hydroxy-9-octadecenoic (ricinoleic) ;
  • Preferred unsaturated fatty acids are selected from the group consisting of: cis-9-octadecenoic; and cis-5,8,11 ,14- eicosatetraenoic.
  • Representative diacylglycerols include, but are not limited to:
  • diarachidin dieicosanoyl-glycerol, reported to be approximately 50% 1 ,3- and 50% 1 ,2-isomer
  • dicaproin dihexanoylglycerol, reported to be 50% 1,3- and 50% 1,2-isomers
  • dilaurin didodecanoylglycerol, reported to be approximately 50% 1,3- and 50% 1,2-isomer
  • dimyristin (ditetradecanoylglycerol, reported to be approximately 50% 1,3- and 50% 1,2-isomer); 18. 1,3-dimyristin (1,3-ditetradecanoylglycerol);
  • diolein di-[(cis)-9-octadecenoyl]glycerol, reported to be approximately 85% 1,3- and 15% 1,2-isomer
  • 1,2-dioleoyl-sn-glycerol (1 ,2-di[(cis)-9- octadecenoylj-sn-glycerol); 26. dipalmitin (dihexadecanoylglycerol, reported to be approximately 50% 1,2- and 50% 1,3-isomer);
  • distearin (dioctadecanoylglycerol, reported to be approximately 50% 1,3- and 50% 1,2-isomer);
  • 1-stearoyl-2-oleoylglycerol (1-octadecanoyl- 2-[(cis)-9- ⁇ ctadecenoylglycerol; and the like.
  • diacylglycerol is selected from the group consisting of:
  • diolein ⁇ 18. 1,3-diolein;
  • the diacylglycerol is selected from the group consisting of: 1,2-dihexanoyl-sn-glycerol; 1,2- . dioctanoyl-rac-glycerol; 1,2-dioctanoyl-sn-glycerol; 1-oleoyl- 2-acetyl-rac-glycerol; 1-oleoyl-2-acetyl-sn-glycerol, or 1- stearoyl-2-arachidonoyl-sn-glycerol. Most preferably 1,2- dioctanoyl-rac-glycerol or 1,2-dioctanoyl-sn-glycerol is used.
  • Diacylglycerols are available commercially from, for example: (1) Sigma Chemical Company, St. Louis, MO. -see Sigma's 1989 catalogue of Biochemicals Organic Compounds for Research and Diagnostic Reagents; (2) Serdary Research Laboratories, Port Huron, Ml; (3) Molecular Probes Inc., Junction City, OR; and (4) Avanti Polar Lipids, Birmingham, AL.
  • Diacylgycerols may also be prepared in accordance with procedures well known in the art, for example see: (1 ) Gunstone et al., editors, The Lipid Handbook pp. 295, et seq., ⁇ 1986; (2) Ebeling et al., Proc. Natl. Acad. Sci. USA, Vol. 82, pp 815-819, at page 816, February 1985; and (3) Ganong et al., Proc. Natl. Acad. Sci. USA, Vol. 83, pp. 1184-1188, March 1986.
  • triacylglycerols may include but are not limited to:
  • tributyrin (1,2,3-tributyrylglyceroi; glyceryl tributyrate); 23. tricaprin (1 ,2,3-tridecanoyiglycerol);
  • trimyristolein (1 ,2,3-tri-[(cis)-9- tetradecenoylj-glycerol) ;
  • triolein (1 ,2,3-tri-[(cis)-9- octadecenoyljglycerol; glyceryl trioleate);
  • tripalmitin (1 ,2,3-trihexadecanoylglycerol) ;
  • tripalmitolein (1 ,2,3-tri-[(cis)-9- hexadecenoylj-glycerol) ;
  • tripentadecanoin (1 ,2,3- tripentadecanoylglycerol);
  • tristearin (1 ,2,3-trioctadecanoylglycerol) ;
  • Triacylglycerols are commercially available from Sigma Chemical Company (same address and catalogue as cited above). Triacylglycerols may also be prepared in accordance with procedures well known in the art, for example see Gunstone et al., editors, The Lipid Handbook ' , p. 295 et seq., ⁇ 1986.
  • LPS Lipopoiysaccharides
  • the active lipid moiety of LPS of Gram-negative bacteria is diacylglucosamine 1 -phosphate.
  • a diacylglucosamine 1 -phosphate or the LPS containing it may be used.
  • the acyl groups of the diacylglucosamine 1 - phosphates from LPS are usually from predominantly C14 to Ci 8 fatty acids which may be saturated or monosaturated, but not polyunsaturated.
  • LPS and bacterial fatty acids see, for example, Davis et al., editors, Microbiology. Third Edition, pp 82 to 91 , ⁇ 1980, the disclosure of which is incorporated herein by reference thereto.
  • bacteria from which LPS can be derived from for use in this invention include, but are not limited to: Escherichia coli (E. coli), Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella abortus equi, Salmonella enteritidis, Salmonella minnesota, Salmonella typhimurium, Salmonella typhosa, Serratia marcescens, Shigelia flexneri, Vibrio cholerae, and the like.
  • Bacterial Lipid A and Lipid X may also prove useful. Lipid A and Lipid X are well known to those skilled in the art. See for example: (1) Wightman et al., The Journal of Biological Chemistry. Vol.
  • Lipid A is commercially available from, for example, Sigma Chemical Company.
  • Lipid X is available from Lipidex, Inc., Middleton, Wl.
  • LPS are available commercially, for example, form Sigma Chemical Co. (already cited above).
  • Examples of LPS available commercially include those derived from: E. coli Serotype 026:B6; E. coli Serotype 055:B5; E. coli Serotype 0111 :B4; E. coli Serotype 0127:B8; E. coli Serotype 0128:B12; E. coli EH-100 (Ra mutant); E. coli F-583 (Rd mutant); E. coli Strain J5 (Re mutant); E.
  • LPS may be derived from bacteria by techniques well known to those skilled in the art.
  • lyophilized powders are available as phenol, trichloroacetic acid (TCA), butanol or phenol-chloroform-petroleum ether extracts.
  • TCA trichloroacetic acid
  • Such procedures are referenced in Sigma Chemical Company's 1989 Biochemicals Organic Compounds catalogue (cited above) as: Westphal et al., Methods in Carbohydrate Chem., 5_, 83 (1965) for a phenol extraction procedure; Staub, Methods in Carbohydrate Chem., 5_, 92 (1965) for a TCA extraction procedure; Lieve et al., Methods in Enzymology, XXVIHb. 254 (1972) for a butanol extraction procedure; and Galanos et al., Eur. J. Biochem., 9_, 245 (1969) for a phenol-chloroform-petroleum ether
  • Unsaturated free fatty acids may also be useful in this invention as PK-C Activators. It is believed that unsaturated free fatty acids having 1 to about 4 double bonds and about 14 to about 20 carbon atoms are preferred PK-C Activators. Cis- and trans-unsaturated free fatty acids are suitable with the proviso that trans-elaidic acid may not be as useful as other unsaturated free fatty acids. Although chain lengths of 14-20 carbon atoms are preferred other chain lengths (less than 14 or more than 20) may also prove useful.
  • Suitable unsaturated free fatty acids may be selected from amongst those unsaturated fatty acids already described above for the acyl groups of the diacylglycerols and triacylglycerols.
  • Preferred unsaturated free fatty acids include linoleic acid, arachidonic acid and oleic acid.
  • Short chain saturated free fatty acids may also prove useful.
  • Suitable saturated free fatty acids may be selected from amongst those saturated fatty acids, having 4 to 10 carbon atoms, described above for the acyl groups of the diacylglycerols and the triacylglycerols.
  • Saturated fatty acids having more than 10 carbon atoms -e.g., 11-20-- may also prove useful.
  • lauric, myristic, palmitic, stearic, and arachidic may be suitable.
  • Another group of compounds which may be useful in this invention as PK-C Activators for enhancing melanin production are glycerophospholipids (phosphoglycerides).
  • Phosphoglycerides consist of a glycerol background, two acyl groups derived from fatty acids (usually bound to the C-1 and C- 2 glycerol carbons) and a phosphorylated alcohol.
  • the major phosphoglycerides are derivatives of phosphatidate (diacylglycerol 3-phosphate).
  • the phosphate group of phosphatidate becomes esterifi to the hydroxyl group of one of several alcohols. Examples of alcohols include serine, threonine, ethanolamine, choline, glycerol, inositol, and the like.
  • the disclosure above pertaining to the acyl groups of the di- and triacylglycerols pertain equally as well to the acyl groups of the phosphoglycerides.
  • phosphoglycerides include, but are not limited to:
  • L- ⁇ -phosphatidylcholine such as that obtained from bovine brain, bovine heart, bovine liver, egg yolk (diced, fresh, frozen or fresh frozen), turkey egg yolk (fresh), and soybean; 2.
  • L- ⁇ -phosphatidylcholine dipentadecanoyl (1 ,2- dipentadecanoyl-sn-glycero-3-phosphocholine); 31 . L- ⁇ -phosphatidylcholine, distearoyl; 32. L- ⁇ -phosphatidylcholine, diundecanoyl (1 ,2- diundecanoyl-sn-glycero-3-phosphocholine);
  • L- ⁇ -phosphatidylethanolamine such as that obtained from bovine brain, sheep brain, egg yolk, soybean, Escherichia coli, dog brain, bovine liver, or porcine liver;
  • phosphatidylethanolamine plasmalogen
  • 65 phosphatidylethanolamine, N-trinitrophenyl
  • 66 L- ⁇ -phosphatidyl-DL-glycerol (1 -[3-sn- phosphatidyl]-rac-glycerol) [prepared by reaction of cabbage phospholipase D with egg yolk L- ⁇ -phosphatidylcholine in the presence of glycerol], including the ammonium salt from egg yolk lecithin and the sodium salt from egg yolk lecithin;
  • L- ⁇ -phosphatidylinositol e.g. from soybean (including the ammonium and sodium salts), and from bovine liver (ammonium salt), as well as TYPE 1 : Folch Fraction 1 from bovine brain reported to contain 10-20% phosphatidyl inositides, 50-60% phosphatidyl serine as well as several other brain Iipids ;
  • 75 phosphoinositides, sodium salt, from bovine brain, Extract Type 1 , reported to contain approximately 15-20% phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-biphosphate with the remainder being a mixture of phosphatidylinositol and phosphatidylserine; 76. L- ⁇ -phosphatidyl-N-monomethylethanolamine, dipalmitoyl ;
  • L- ⁇ -phosphatidyl-L-serine e.g., from bovine brain (including the sodium salt), as well as TYPE III: Folch Fraction III from bovine brain reported to contain 80-85% phosphatidylserine with the balance being other brain Iipids; 79. L- ⁇ -phosphatidylserine, dansyl; and
  • PK-C Activator is in a concentration which is effective to provide the desired level of activity.
  • the PK-C Activator may be used in amounts of about 0.01% to about 20% by weight of the total composition with about 0.05% to about 10% being preferred and about 0.05% to about 1.0% being most preferred.
  • Combinations of PK-C Activators may be used such that their total amount is within the specified ranges.
  • Suitable solvents for use with the PK-C Activators include liposomes; ketones such as acetone and the like; alcohols such as benzyl alcohol, ethanol, t-butyl alcohol, cetyl alcohol, glycol (HOCH2CH2OH), isopropyl alcohol, propylene glycol, SD alcohol 23-A, SD alcohol 39-C, SD alcohol 40, SD alcohol 40-B and the like; Fats and oils such as avocado oil, cocoa butter, coconut oil, corn oil, hydrogenated coconut oil, hydrogenated cottonseed oil, hydrogenated vegetable oil, lanolin oil, mink oil, palm oil, peanut oil, safflower oil, soybean oil, sunflower seed oil, sweet almond oil, vegetable oil (expressed oil of vegetable origin consisting primarily of triglycerides of fatty acids), walnut oil, wheat germ oil and the like; hydrocarbons such as mineral oil and the like; alkoxylated alcohols or polymeric ethers such as PEG-8, PEG-14M and the like; lanolin and lan
  • the liposomes may also be used as a solvent for the PK-C Activators or may used to blend with the PK-C Activators so that the PK-C Activators are in the lipid layer.
  • the riboflavin, riboflavin phosphate or mixtures thereof may be combined with the PK-C Activators and the resultant combination may be encapsulated in liposomes.
  • PK-C Activators are lipophilic, it may be desirable to add components to the water when making up aqueous solutions for encapsulation in liposomes. These added components would be water miscible and would improve the water solubility of the PK-C Activators. These components may include solvents such as alcohols and ketones already discussed above.
  • compositions containing PK-C Activators immediately after they are prepared or to freeze them at about -20°C until they are used. If this is not convenient then it is necessary to add an effective amount of at least one antioxidant to protect the PK-C Activator from degradation. However, if a PK-C Activator is used which will not degrade over time then an antioxidant is no longer necessary but its use is still preferred. Generally, about 0.05 to about 0.10% by weight of the total composition of an antioxidant is sufficient. Any of the antioxidants known for use in the cosmetics industry may be used.
  • antioxidants include but are not limited to beta-carotene, BHA, BHT, a- tocopherol, propyl gallate, sodium bisulfite, sodium metabisulfite, ascorbyl dipalmitate, TENOX (trademark for food grade antioxidants reported to contain one or more of the following ingredients: butylated hydroxyanisole, butylated hydroxytoluene, and/or propyl gallate with or without citric acid; some formulas are supplied in solvents such as propylene glycol), and the like. See, for example CTFA Cosmetic Ingredient Handbook cited above.
  • At least one antioxidant may be added to the compositions containing riboflavin, riboflavin phosphate or mixtures thereof but no PK-C Activator.
  • the amount of antioxidant used would be the same as discussed above for use with the PK-C Activators.
  • DOPA phosphates can be used in amounts of about 0.005% to about 1.0% by weight of the total composition with about 0.015% to about 0.5% being preferred and about 0.05% to about 0.02% being most preferred.
  • DOPA phosphates (phosphodopas) are O- phosphorylated derivatives of DOPA.
  • the DOPA phosphates are represented by Formulas I-V:
  • R "1 and R 2 each represent hydrogen or
  • R 4 and R3 each represent hydrogen or a pharmaceutically acceptable cation; with the proviso that R and R 2 cannot both be hydrogen.
  • the sunscreening agents used can be of the UVA type,
  • the sunscreening agents are used in amounts effective to provide the desired level of protection against UVA and/or UVB radiation.
  • the sunscreening agents are used in amounts of about 2% to about 20% by weight of the total composition with about 5% to about 18% being preferred and about 2% to about 15% being most preferred.
  • Typical UVB type sunscreening agents include substituted para-aminobenzoates, alkyl esters of para- methoxycinnamate and certain esters of salicylic acid.
  • Typical UVA type sunscreening agents include certain benzophenones and dibenzoyl methanes.
  • UVB type sunscreening agents include but are not limited to:
  • DEA Methoxyinnamate diethanolamine salt of p-methoxy hydro cinnamate
  • BERNEL HYDRO from Bernel Chemical Co., Inc.
  • Ethyl Dihydroxypropyl PABA ethyl dihydroxypropyl p-aminobenzoate
  • AMERSCREEN P from Amerchol Corp.
  • Glyceryl PABA glyceryl-p-aminobenzoate
  • NIPA G.M.P.A tradename NIPA Laboratories, Inc.
  • Homosalate Homomenthyl salicylate
  • KEMESTER HMS from Humko
  • PABA p-amino benzoic acid
  • PABA p-amino benzoic acid
  • EM Industries, Inc. and National Starch & Chemical Corp. or tradename NIPA PABA from NIPA Laboratories Inc.
  • NIPA PABA from NIPA Laboratories Inc.
  • NEO-HELIOPAN HYDRO from EM Industries, Inc. and Haarmann & Reimer Corp., respectively;
  • TEA Salicylate triethanolamine salicylate
  • tradenames SUNAROME W and SUNAROME G from Felton Worldwide, Inc. e.g., tradenames SUNAROME W and SUNAROME G from Felton Worldwide, Inc.
  • UVA type sunscreening agents include but are not limited to:
  • UV-9 and UVINUL M-40 from American Cyanamid Co. and BASF Chemical Co., respectively;
  • Benzophenone-4 sulisobenzone
  • UVINUL MS-40 from BASF Chemical Co.
  • C Benzophenone-8 (dioxybenzone), e.g., tradename SPECTRA-SORB UV-24 from American Cyanamid Co.
  • Menthyl Anthranilate (Menthyl-O- aminobenzoate), e.g., tradename SUNAROME UVA from Felton Worldwide, Inc.;
  • Benzophenone-12 (octabenzone), e.g., tradename UVINOL 408 from BASF Chemical Co.;
  • 3-phenylpropane-1 ,3-dione e.g. tradename EUSOLEX 8020 from EM Industries, Inc.; and
  • Physical sunscreening agents may also be used.
  • red petrolatum in amounts of about 30 to about 99% by weight of the total composition, or titanium dioxide in amounts of about 2 to about 25% by weight of the total composition may be used.
  • Talc, kaolin, chalk , and precipitated silica may also be used in effective amounts, e.g., about 1% to about 10% by weight of the total composition.
  • Additional sunscreening agents include lawsone
  • At least one UVB type and at least one UVA type sunscreening agent is used.
  • at least one of the following UVB type sunscreening agents can be used: from about 1.5 to about 8.0% by weight of the total composition of octyl dimethyl PABA; octyl para- methoxycinnamate in amounts of about 1.5 to about 7.5% by weight of the total composition; homomenthyl salicylate in amounts of about 4.0 to about 15% by weight of the total composition; and octyl salicylate in amounts of about 3 to about 5% by weight of the total composition.
  • UVA type sunscreening agents can be used: benzophenone-3 in amounts of about 0.5 to about 6% by weight of the total composition; benzophenone-8 in amounts of about 0.5 to about 3% by weight of the total composition; and menthyl anthranilate in amounts of about 3.5 to about 5.0% by weight of the total composition.
  • the ingredients disclosed above e.g., emollients, emulsifiers, film formers, and the like
  • the riboflavin, riboflavin phosphate or mixtures thereof can be incorporated into formulations such as lotions, creams, gels mousses, waxed based sticks, aerosols, alcohol sticks and the like.
  • Emollients may be used in amounts which are effective to prevent or relieve dryness.
  • Useful emollients may include: hydrocarbon oils and waxes; silicone oils; triglyceride esters; acetoglyceride esters; ethoxylated glyceride; alkyl esters; alkenyl esters; fatty acids; fatty alcohols; fatty alcohol ethers; ether-esters; lanolin and derivatives; polyhydric alcohols (polyols) and polyether derivatives; polyhydric alcohol (polyol) esters; wax esters; beeswax derivatives; vegetable waxes; phospholipids; sterols; and amides.
  • typical emollients include mineral oil, especially mineral oils having a viscosity in the range of 50 to 500 SUS, lanolin oil, mink oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extract, jojoba oil, safflower oil, corn oil, liquid lanolin, cottonseed oil, peanut oil, purcellin oil, perhydrosqualene (squalene), caster oil, polybutene, odorless mineral spirits, sweet almond oil, avocado oil, calophyllum oil, ricin oil, vitamin E acetate, olive oil, mineral spirits, cetearyl alcohol (mixture of fatty alcohols consisting predominantly of cetyl and stearyl alcohols), linolenic alcohol, oleyl alcohol, octyl dodecanol, the oil of cereal germs such as the oil of wheat germ cetearyl octanoate (ester of cetearyl alcohol and 2-
  • Emulsifiers may be used in amounts effective to provide uniform blending of ingredients of the composition.
  • Useful emulsifiers may include
  • Fatty acid soaps e.g., potassium stearate, sodium stearate, ammonium stearate, and triethanolamine stearate
  • Polyol fatty acid monoesters containing ' fatty acid soaps e.g., glycerol monostearate containing either potassium or sodium salt
  • Sulfuric esters sodium salts
  • Polyol fatty acid monoesters containing sulfuric esters e.g., glyceryl monostearate containing sodium lauryl ' sulfate
  • polyoxyethylene fatty alcohol ethers e.g., polyoxyethylene lauryl alcohol
  • polyoxypropylene fatty alcohol ethers e.g., propoxylated oleyl alcohol
  • polyoxyethylene fatty acid esters e.g., polyoxyethylene stearate
  • polyoxyethylene sorbitan fatty acid esters e.g. polyoxyethylene sorbitan monostearate; 7168
  • sorbitan fatty acid esters e.g., sorbitan monostearate
  • polyoxyethylene glycol fatty acid esters e.g., polyoxyethylene glycol monostearate
  • polyol fatty acid esters e.g., glyceryl monostearate and propylene glycol monostearate
  • ethoxylated lanolin derivatives e.g., ethoxylated lanolins, ethoxylated lanolin alcohols and ethoxylated cholesterol.
  • Surfactants may also be used in the compositions of this invention.
  • Suitable surfactants may include those generally grouped as cleansing agents, emulsifying agents, foam boosters, hydrotropes, solubilizing agents, suspending agents and nonsuriactants (facilitates the dispersion of solids in liquids).
  • the surfactants are usually classified as amphoteric, anionic, cationic and nonionic surfactants.
  • Amphoteric surfactants include acylamino acids and derivatives and N-alkylamino acids.
  • Anionic surfactants include: acylamino acids and salts, such as, acylglutamates, acylpeptides, acylsarcosinates, and acyltaurates; carboxylic acids and salts, such as, alkanoic acids, ester carboxylic acids, and ether carboxylic acids; sulfonic acids and salts, such as, acyl isethionates, alkylaryl sulfonates, alkyl suifonates, and sulfosuccinates; sulfuric acid ' esters, such as, alkyl ether sulfates and alkyl sulfates.
  • acylamino acids and salts such as, acylglutamates, acylpeptides, acylsarcosinates, and acyltaurates
  • carboxylic acids and salts such as, alkanoic acids, ester carboxylic acids, and ether carboxylic acids
  • Cationic surfactants include: alkylamines, alkyl imidazolines, ethoxylated amines, and quaternaries (such as, alkylbenzyldimethyiammonium salts, alkyl betaines, heterocyclic ammonium salts, and tetra alkylammonium salts).
  • Nonionic surfactants include: alcohols, such as primary alcohols containing 8 to 18 carbon atoms; alkanolamides such as alkanolamine derived amides and ethoxylated amides; amine oxides; esters such as ethoxylated carboxylic acids, ethoxylated glycerides, glycol esters and derivatives, monoglycerides, polyglyceryl esters, polyhydric alcohol esters and ethers, sorbitan/sorbitol esters, and triesters of phosphoric acid; and ethers such as ethoxylated alcohols, ethoxylated lanolin, ethoxylated polysiloxanes, and propoxylated polyoxyethylene ethers.
  • Useful solvents for sunscreening agents include those solvents already disclosed as being useful solvents for the PK-C Activators.
  • Suitable waxes which may prove useful include: animal waxes, such as beeswax, spermaceti, or wool wax (lanolin); plant waxes, such as carnauba or candelilla; mineral waxes, such as montan wax or ozokerite; and petroleum waxes, such as paraffin wax and microcrystalline wax (a high molecular weight petroleum wax).
  • animal waxes such as beeswax, spermaceti, or wool wax (lanolin); plant waxes, such as carnauba or candelilla; mineral waxes, such as montan wax or ozokerite; and petroleum waxes, such as paraffin wax and microcrystalline wax (a high molecular weight petroleum wax).
  • animal waxes such as beeswax, spermaceti, or wool wax (lanolin)
  • plant waxes such as carnauba or candelilla
  • mineral waxes such as montan wax or ozokerite
  • petroleum waxes such as
  • Suitable waxes which may be useful also include the synthetic waxes including polyethylene polyoxyethylene and hydrocarbon waxes derived from carbon monoxide and hydrogen (Fischer-Tropsch synthesis).
  • Representative waxes also include: ceresin; cetyl esters; hydrogenated jojoba oil; hydrogenated jojoba wax; hydrogenated rice bran wax; Japan wax; jojoba butter; jojoba oil; jojoba wax; munk wax; montan acid wax; ouricury wax; rice bran wax; shellac wax; sufurized jojoba oil; synthetic beeswax; synthetic jojoba oils; trihydroxystearin; cetyl alcohol; stearyl alcohol; cocoa butter; fatty acids of lanolin; mono-, di- and triglycerides which are solid at 25°C, e.g., glyceyl tribehenate (a triester of behenic acid and glycerine) and C18-C36 acid triglyceride (a mixture of triesters of C1 8-C36 carboxylic acids and glycerine) available from Croda, Inc., New York, NY under the tradenames Syncrowax HR
  • Thickeners which may be used in effective amounts in aqueous systems include: algin; carbomers such as carbomer 934, 934P, 940 and 941 ; cellulose gum; cetearyl alcohol, cocamide DEA, dextrin; gelatin; hydroxyethylcellulose; hydroxypropylcelluiose; hydroxypropyl methylcellulose; magnesium aluminum silicate; myristyl alcohol; oat flour; oleamide DEA; oleyl alcohol; PEG-7M; PEG-
  • DEA diethanolamine
  • MEA monoethanolamine
  • Thickeners which may be used in effective amounts in nonaqueous systems include, aluminum stearates; beeswax; candelilla wax; carnauba; ceresin; cetearyl alcohol; cetyl alcohol; cholesterol; hydrated silica; hydrogenated castor oil; hydrogenated cottonseed oil; hydrogenated soybean oil; hydrogenated tallow glyceride; hydrogenated vegetable oil; hydroxypropyl cellulose; lanolin alcohol; myristyl alcohol; octyldodecyl stearoyl sulfate; oleyl alcohol; ozokerite; microcystalline wax; paraffin; pentaerythrityl tetraoctanoate; polyacrylamide; polybutene; polyethylene; propylene glycol dicaprylate; propylene glycol dipelargonate; stearalkonium hectorite; stearyl alcohol; stearyl stearate; synthetic bees
  • Suitable film formers which may be used include: acrylamide/sodium acrylate copolymer; ammonium acrylates copolymer; Balsam Peru; cellulose gum; ethylene/maieic anhydride copolymer; hydroxyethylcellulose; hydroxypropylcelluiose; polyacrylamide; polyethylene; polyvinyl alcohol; pvm/MA copolymer (polyvinyl methylether/ maleic anhydride); PVP (polyvinylpyrroiidone); maleic anhydride copolymer such as PA-18 available from Gulf Science and
  • film formers can be used in amounts of about 0.1% to about 10% by weight of the total composition with about 1% to about 8% being preferred and about 0.1% to about 5% being most preferred.
  • Preservatives which may be used in effective amounts include: butylparaben; ethylparaben; ;midazolidinyl urea; methylparaben; O-phenylphenol; propylparaben; quaternium-14; quaternium-15; sodium dehydroacetate; zinc pyrithione; and the like.
  • the preservatives are used in amounts effective to prevent or retard microbial growth. Generally, the preservatives are used in amounts of about 0.1% to about 1% by weight of the total composition with about 0.1% to about ⁇ .8% being preferred and about 0.1% to about 0.5% being most preferred.
  • Perfumes fragment components
  • colorants coloring agents
  • ingredients which may by added or used in amounts effective for their intended use include: biological additives to enhance performance or consumer appeal such as amino acids, proteins, vanilla, aloe extract, bioflavinoids, and the like; buffering agents; chelating agents such as EDTA; emulsion stabilizers; pH adjusters; opacifying agents; and propellants such as butane carbon dioxide, ethane, hydrochlorofluorocarbons 22 and 142b, . hydrofluorocarbon 152a, isobutane, isopentane, nitrogen, nitrous oxide, pentane, propane, and the like.
  • ingredients --sunscreening agents, emollients, emulsifiers, surfactants, solvents for sunscreening agents, waxes, thickeners, film formers, humectants, preservatives, surfactants, perfumes, coloring agents, biological additives, buffering agents, chelating agents, emulsion stabilizers, opacifying agents, pH adjusters, and propellants- are all well known to those skilled in the art, and the determination of which ingredients to use to obtain the intended formulations (lotions, creams, gels, sticks, and aerosols), and determination of the variations in the amounts which may be used to achieve the intended functions and effects of these ingredients are well within the capabilities of those skilled in the art without the need for undue experimentation. Further information may be obtained on these ingredients by reference to:
  • riboflavin, riboflavin phosphate or mixtures thereof not be subjected to heating or to high alkaline conditions. If PK-C Activators are used they should not be heated nor subjected to high alkaline conditions.
  • a typical lotion formulation is listed in Table 1.
  • Emcol RHT (Glyceryl Stearate) 1
  • Part A and Part C (Table 2) were heated to about 77-82°C. Then Part A was stirred into Part C. Part B was added to the mixture formed from Parts A and C. The resulting mixture of Parts A, C and B was force cooled to 65°C. The ingredients in Part D were dissolved together and then added at about 45-50°C to the mixture of Parts A, C, and B. To this resulting mixture there was added the ingredients of Part E at about 42-45°C, and the final mixture was mixed until the temperature of the mixture reached room temperature (about 25°C).
  • formulations which may prove useful which are oil-in-water creams, oil-in-water lotions, water-in- oil lotions, oil-in-water resistant creams and lotions, sticks, gels, oils and mousses may be found in, for example, Cosmetics & Toiletries, Vol. 102, pp 117-1 ⁇ 0, March 1987, the disclosure of which is incorporated herein by reference thereto.
  • formulations which may prove useful which are hand and body lotions, oil-in-water emollient creams, moisturizing lotions, after sun emollient stick, facial spray mist, skin mousse and moisturizing gel may be found, for example, in Cosmetics & Toiletries, Vol.
  • compositions containing riboflavin in amounts of 0.02% and 0.2% by weight of the total composition were studied.
  • the vehicle was Coppertone After Tan Lotion, commercially available from Plough Inc., Memphis, TN.
  • the vehicle composition would be similar to that given in Table 1 above.
  • Each group received topical treatment daily (Monday to Friday) to their dorsal surface (12 cm 2 ) of 2 ⁇ l/cm 2 of the appropriate vehicle or composition for four weeks. Irradiations were performed three times weekly (Monday, Wednesday and Friday) over the four week time period. The irradiations were performed using a 20 minute exposure each time from a bank of Kodacel 401 -filtered FS-20 lamps. The mice were housed in a room lighted by F40GO gold fluorescent lamps. The test solutions were stored refrigerated in the dark when not in use.
  • DOPA stains were done on epidermal sheets and Warthin-Starry melanin stains were done on thin sections in accordance with procedures well known to those skilled in the art (see, for example, Luna, L., Manual of Histolooic Staining Methods of the Armed Forces Institute of Pathology. McGraw-Hill Book Co., New York, 1968.
  • Ten random fields on DOPA stained sections were counted at 100x magnification and a group mean calculated.
  • Tests of melanocytes seen on Warthin-Starry sections were scored from +1 (a few melanocytes) to +4 (extensive melanization) and a mean score per slide for each group calcuated. The results are given in Table 3.
  • Group DOPA Group Mean
  • Example 1 The procedures of Example 1 were followed except that each group had 6 mice and the irradiations were conducted for three weeks. The results are given in Table 4.
  • Group DOPA Group Mean
  • Irradiation templates were devised with two circular holes, one inch apart, of 2 cm diameter each, providing two application sites of 12.57 cm 2 .
  • Each subject's arm was examined and templates were placed to expose sites on the lightly pigmented, hairless, inside forearm. Reference points outside the treatment area were marked with Castaderm for template alignment.
  • the upper site, designated site I was spaced approximately two inches from the inside bend of the elbow.
  • the irradiation source was a bank of 4 Kodacel 401 -filtered FS20 bulbs in a shuttered housing.
  • the subject's skin was approximately 3 inches from the Kodacel filtered shutter. Both sites were irradiated simultaneously.
  • Results are set forth in Tables 5 and 6.
  • I indicates Site I which was treated with the lotion containing 0.2% riboflavin
  • II indicates Site II which was the control
  • column "C” gives the results of the comparison of Sites I and II indicating which site is darker as scored by the investigator.
  • Example 4 the group responding with the greatest pigmentation increase (melanocyte count) over the control group was the group treated with 0.01% DOPA phosphate (mixture of Isomers II and III) plus 0.2% riboflavin.
  • the response in the earlier experiment could not be shown to be statistically different from the response due to 0.2% riboflavin alone. - This may have been due to the degradation of DOPA phosphate Isomer II since the lotion was not stored refrigerated in the earlier experiment.
  • the difference in the results set forth in Table 7 are statistically significant.
  • the total amount of all ingredients (components) used in the compositions of this invention equals 100% by weight of the total composition. Also, unless stated otherwise all percents and amounts are percent by weight of the total composition.

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Abstract

Selon un procédé de promotion de la production in vivo de mélanine, on applique topiquement une quantité efficace de riboflavine, de phosphate de riboflavine ou de mélanges de ceux-ci à la surface de la peau. Une composition qui améliore la production in vivo de mélamine comprend une quantité efficace de riboflavine, de phosphate de riboflavine ou de mélanges de ceux-ci. La composition peut contenir au moins un autre ingrédient sélectionné dans le groupe formé des activateurs C de la kinase de protéine, des phosphates DOPA, des agents de protection contre la lumière du soleil, des émollients, des émulsifiants, des solvants des agents de protection contre la lumière du soleil, des cires, des épaississants, des agents filmogènes, des humidificateurs, des antioxydants, des agents conservateurs, des agents tensio-actifs, des parfums, des additifs biologiques, des agents de tamponnement, des chélateurs, des stabilisateurs de l'émulsion, des opacifiants, des agents d'ajustement du pH, des propulseurs et des colorants. Les activateurs C de la kinase de protéine présents dans les compositions décrites peuvent être sélectionnés dans le groupe formé des diacylglycérols, des triacylglycérols, des lipopolysaccharides, des acides gras libres insaturés, des acides gras libres saturés à courte chaîne, des glycérolphospholipides, des enzymes qui hydrolysent les glycophospholipides en diacylglycérols et des bryostatines.
PCT/US1990/006328 1989-11-09 1990-11-07 Riboflavine comme promoteur du tannage WO1991007168A1 (fr)

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WO1992017173A2 (fr) * 1991-04-02 1992-10-15 Jean Berque Utilisation de la riboflavine dans le traitement de maladies liees aux virus hiv, de l'herpes, de la retinite pigmentaire et du paludisme
WO1994004122A2 (fr) * 1992-08-21 1994-03-03 Trustees Of Boston University Application de diacylglycerols pour accroitre la teneur en melanine des melanocytes
US5470577A (en) * 1993-07-07 1995-11-28 Trustees Of Boston University Stimulation of tanning by DNA fragments or single-stranded DNA
WO1996009810A1 (fr) * 1994-09-28 1996-04-04 Trustees Of Boston University Procedes permettant d'accroitre la synthese de melanine dans les melanocytes par l'emploi de diacylglycerols, et utilisations de ces procedes
EP0796077A1 (fr) * 1994-12-20 1997-09-24 Maybelline Intermediate Co. Composition de maquillage revitalisante
GB2302505B (en) * 1994-06-03 1998-06-24 Secr Defence Stabilisation of photosensitive materials
WO2012001064A3 (fr) * 2010-06-30 2012-03-22 Galderma Research & Development Procédé de prévention ou de traitement des tumeurs cutanées
WO2012001065A3 (fr) * 2010-06-30 2012-03-29 Galderma Research & Development Méthode de prévention ou de traitement des tumeurs cutanées
KR20160020218A (ko) * 2014-08-13 2016-02-23 주식회사 엘지생활건강 모노미리스틴 또는 이의 약학적으로 허용가능한 염을 포함하는 흑화, 탄력, 주름개선, 보습 또는 항염증용 화장료 또는 약학 조성물

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CH642537A5 (en) * 1980-01-25 1984-04-30 Uni Chemie Ag Cosmetic sunscreen product
FR2624374A1 (fr) * 1987-12-09 1989-06-16 Induchem Ag Preparation, notamment cosmetique antisolaire, et procede pour faire passer une substance active dans la peau
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Cited By (23)

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US5750091A (en) * 1988-03-30 1998-05-12 The Trustees Of Boston University Methods for increasing melanin content in melanocytes using diacylglycerols and uses thereof
US5352440A (en) * 1988-03-30 1994-10-04 Trustees Of Boston University Methods for increasing melanin content in melanocytes using diacylglycerols and uses thereof
US5700450A (en) * 1988-03-30 1997-12-23 The Trustees Of Boston University Methods for enhancing melanin synthesis in melanocytes using diacyglycerols and uses thereof
WO1992017173A3 (fr) * 1991-04-02 1993-01-07 Jean Berque Utilisation de la riboflavine dans le traitement de maladies liees aux virus hiv, de l'herpes, de la retinite pigmentaire et du paludisme
WO1992017173A2 (fr) * 1991-04-02 1992-10-15 Jean Berque Utilisation de la riboflavine dans le traitement de maladies liees aux virus hiv, de l'herpes, de la retinite pigmentaire et du paludisme
WO1994004122A2 (fr) * 1992-08-21 1994-03-03 Trustees Of Boston University Application de diacylglycerols pour accroitre la teneur en melanine des melanocytes
WO1994004122A3 (fr) * 1992-08-21 1994-03-31 Univ Boston Application de diacylglycerols pour accroitre la teneur en melanine des melanocytes
US5643556A (en) * 1993-07-07 1997-07-01 Trustees Of Boston University Stimulation of tanning by DNA fragments or single-stranded DNA
US5580547A (en) * 1993-07-07 1996-12-03 Trustees Of Boston University Stimulation of tanning by DNA fragments or single-stranded DNA
US5532001A (en) * 1993-07-07 1996-07-02 Trustees Of Boston University Stimulation of tanning by DNA fragments or single-stranded DNA
US5470577A (en) * 1993-07-07 1995-11-28 Trustees Of Boston University Stimulation of tanning by DNA fragments or single-stranded DNA
GB2302505B (en) * 1994-06-03 1998-06-24 Secr Defence Stabilisation of photosensitive materials
WO1996009810A1 (fr) * 1994-09-28 1996-04-04 Trustees Of Boston University Procedes permettant d'accroitre la synthese de melanine dans les melanocytes par l'emploi de diacylglycerols, et utilisations de ces procedes
EP0796077A1 (fr) * 1994-12-20 1997-09-24 Maybelline Intermediate Co. Composition de maquillage revitalisante
EP0796077A4 (fr) * 1994-12-20 1998-03-04 Maybelline Intermediate Corp Composition de maquillage revitalisante
WO2012001064A3 (fr) * 2010-06-30 2012-03-22 Galderma Research & Development Procédé de prévention ou de traitement des tumeurs cutanées
WO2012001065A3 (fr) * 2010-06-30 2012-03-29 Galderma Research & Development Méthode de prévention ou de traitement des tumeurs cutanées
CN103209690A (zh) * 2010-06-30 2013-07-17 盖尔德马研究及发展公司 α肾上腺素能受体激动剂用于预防或治疗皮肤肿瘤的用途
US8911713B2 (en) 2010-06-30 2014-12-16 Galderma Research & Development Method for preventing or treating skin tumor
CN104288768A (zh) * 2010-06-30 2015-01-21 盖尔德马研究及发展公司 α2-肾上腺素能受体激动剂的用途
US9554988B2 (en) 2010-06-30 2017-01-31 Galderma Research & Development Method for preventing or treating skin tumor
KR20160020218A (ko) * 2014-08-13 2016-02-23 주식회사 엘지생활건강 모노미리스틴 또는 이의 약학적으로 허용가능한 염을 포함하는 흑화, 탄력, 주름개선, 보습 또는 항염증용 화장료 또는 약학 조성물
KR102104305B1 (ko) * 2014-08-13 2020-04-24 주식회사 엘지생활건강 모노미리스틴 또는 이의 약학적으로 허용가능한 염을 포함하는 흑화, 탄력, 주름개선, 보습 또는 항염증용 화장료 또는 약학 조성물

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