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|||||III USOO575O123A United States Patent (19) 11 Patent Number: 5,750,123 Znaiden et al. 45 Date of Patent: May 12, 1998

54 VITAMIN C DELIVERY SYSTEM 4,869.897 9/1989 Chatterjee et al...... 424/47 4923.900 5/1990 De Willez. 75 Inventors: Alexander Paul Znaiden. Trumbull; 4,983,382 l/1991 Wilmott et al. . Brian Andrew Crotty,K- Branford; 3.5,137.723 8/1992E. YamamotoE. et "O"... 4: Anthony Johnson. Fairfield, all of 5,140.043 8/1992 Darret al...... 514,474 5,462.963 O/1995 Bush et al...... 5248 73) Assignee: Chesebrough-Pond's Co., Division of FOREIGN PATENT DOCUMENTS Conopco, Inc.. Greenwich. Conn. 44-22312 9/1969 Japan. 90/12752 11/1990 WIPO (21) Appl. No.: 696,422 OTHER PUBLICATIONS (22 Filed: Aug. 13, 1996 Chemical Abstracts vol. 105, No. 20. Nov. 17, 1986, Related U.S. Application Data Abstract No. 178434. Primary Examiner-Jyothsan Venkat 60 Provisional application No. 60022,509, Jun. 28, 1996. Attorney, Agent, or Fi Milton L. Honig 51) int. Cl.6 ...... A61K A18 57 ABSTRACT 52 U.S. Cl...... 424/401; 514/474: 514/844 58) Field of Search ...... 424/401: 514/474, A cosmetic composition is provided which includes ascorbic 54/844 acid (Vitamin C) stabilized by dimethyl isosorbide in a pharmaceutically acceptable carrier. Among the preferred 56 References Cited carriers are such as , and mixtures thereof. Aesthetic properties are U.S. PATENT DOCUMENTS improved by the presence of a crosslinked non-emulsifying 4.228,162 O/1980 Luzzi et al. . siloxane elastomer and a volatile siloxane. 4,372,874 2/1983 Modrovich ...... 436/76 4.818,521 4/1989 Tamabuchi. 7 Claims, No Drawings 5,750,123 1 2 WTAM N C DELVERY SYSTEM variety of glycols. These include polyethylene glycol, eth ylene glycol, diethylene glycol and even ethanol. These This application claims the benefit of a U.S. Provisional formulations are intended for ingestion. Application 60/0225.09 filed Jun. 28, 1996 now abandoned. U.S. Pat. No. 4372,874 (Modrovich) has reported incor BACKGROUND OF THE INVENTION poration of relatively large amounts of ascorbic acid in a polar water-miscible organic solvent such as dimethyl sul 1. Field of the Invention foxide. Levels of water are kept below 0.5% through addi The invention relates to a cosmetic product that can stably tion of a particulate desiccant to the carrier. Although highly store ascorbic acid and then deliver same to the skin. polar systems such as dimethyl sulfoxide may be effective. 2. The Related Art 10 this and related carriers are toxicologically questionable. Ascorbic acid, also known by its common name of Accordingly, it is an object of the present invention to Vitamin C. has long been recognized as an active substance provide a delivery system for ascorbic acid in which the benefiting skin appearance. Vitamin C reportedly increases compound is soluble or at least uniformly dispersible and the production of collagen in human skin tissue. Wrinkles oxidatably storage stable. and fine lines are thereby reduced. An overall healthier and 15 Another object of the present invention is to provide a younger-looking appearance results. Vitamin C has also delivery system which assists the penetration of ascorbic found utility as an ultraviolet ray blocking or absorbing agent. Whitening or bleaching skin compositions have also acid into the human skin while avoiding irritation thereof. employed Vitamin C utilizing its property of interference Still another object of the present invention is to provide with the melanin formation process. There also is a belief a system for delivering ascorbic acid that is aesthetically that ascorbic acid interacts with the human immune system pleasing and imparts a soft and smooth skinfeel. to reduce sensitivity to skin aggravating chemicals, Reduced These and other objects of the present invention will levels of Vitamin C concentration on the skin have also been become more readily apparent through the following implicated with an increase in stress. From all of the summary, detailed discussion and Examples. foregoing perspectives. Vitamin C or ascorbic acid may 25 provide significant benefit when topically applied. SUMMARY OF THE INVENTION Unfortunately, Vitamin C is a very unstable substance. A cosmetic composition is provided that includes: Although it is readily soluble in water, rapid oxidation (i) from 0.001 to 50% by weight of ascorbic acid; occurs in aqueous media. Solubility of ascorbic acid has (ii) from 0.1 to 20% by weight of dimethyl isosorbide; and been reported to be relatively poor in nonaqueous media, 30 (iii) a pharmaceutically acceptable carrier present in an thereby preventing an anhydrous system from achieving any effective amount to deliver the ascorbic acid to skin. significant level of active concentration. A system is neces sary for dissolving or at least uniformly suspending Vitamin DETALED DESCRIPTION OF THE C which is also chemically compatible with the active, INVENTION The art has sought to overcome the problem in a variety 35 Now it has been discovered that ascorbic acid can be of ways. One approach is the preparation of ascorbic acid stabilized against decomposition and uniformly dispersed derivatives. These derivatives have greater stability than the through use of dimethyl isosorbide in a pharmaceutically parent compound and through biotransformation or chemi acceptable carrier. Dimethyl isosorbide is known in Chemi cal hydrolysis. can at the point of use be converted to the cal Abstracts as 1.4:3.6 dianhydro-2,5-di-o-methyl-D- parent acid. For instance, U.S. Pat. No. 5,137,723 glucitol. Commercially it is available from ICI Surfactants (Yamamoto et al) and U.S. Pat. No. 5,078.989 (Ando et al) under the trademark Arlasolve DMI. Amounts of this mate provide glycosylate and ester derivatives, respectively. rial may range from 0.1 to 20%, preferably from 0.5 to 10%. U.S. Pat. No. 4.818,521 (Tamabuchi) describes under the optimally from 1 to 8% by weight. background technology a so-called two-pack type cosmetic 45 Ascortbic acid is available from several sources including wherein Vitamin C powder and other ingredients are sepa Roche Chemicals. Amounts of this material may range from rately packaged in different containers with mixing just prior 0.001 to 50%, preferably from 0.1 to 10%, optimally from to use of the cosmetic. The mixing procedure and expensive 1 to 10% by weight. packaging were said to be drawbacks of this system. The Compositions of this invention will require a pharmaceu patent suggests stable oil-in-water type emulsions that are SO tically acceptable carrier. Generally the carrier will be an weakly acidic and wherein ascorbic acid has been premixed ingredient present in highest amounts in the cosmetic com with a stabilizing oil. position. These amounts may range from 10 to 99.9%. Maintenance of pH below about 3.5 has also been sug preferably from 25 to 90%, optimally from 50 to 85% by gested in U.S. Pat. No. 5.140,043 (Darret al) as a stabili weight. Pharmaceutically acceptable carriers may be zation means for aqueous compositions of ascorbic acid. 55 selected from water, polyols, silicone fluids, esters and Water compatible such as propylene glycol, mixtures thereof. When present, water may range from 0.5 polypropylene glycol and have been suggested as to 20%, preferably from 1 to 10%, usually from 2 to 6%. co-carriers alongside water to improve stability. An illustra optimally less than 5% by weight of the composition. tion of this approach can be found in U.S. Pat. No. 4,983.382 Advantageously one or more polyols are present as car (Wilmott and Znaiden). Therein a blend of water and water riers in the compositions of this invention. Illustrative are miscible organic solvent are combined as a stabilizing propylene glycol, dipropylene glycol, polypropylene glycol, system. At least about 40% of the organic solvent must be polyethylene glycol, , hydroxypropyl sorbitol, hexy ethanol while the remainder may be selected from such lene glycol. 1.3-butylene glycol, 1.2.6-hexanetriol, glycerin, alcohols as propylene glycol, glycerin, dipropylene glycol ethoxylated glycerin, propoxylated glycerin and mixtures and polypropylene glycol. 65 thereof. Most preferably the is a mixture of polyeth Japanese Patent 44-22312 (Shionogi) describes the stabi ylene glycol, molecular weight ranging from 200 to 2,000, lization of Vitamin C in a mainly aqueous medium by a and propylene glycol. Preferred weight ratios of polyethyl 5,750,123 3 4 ene glycol to propylene glycol range from 5:1 to 1:10, isopropyl isostearate. diisopropyl adipate, diisohexyl preferably from 2:1 to 1:5, optimally 1:1 to 1:2. Amounts of adipate, dihexyldecyl adipate. diisopropyl sebacate, lauryl the polyol may range from 1 to 50%, preferably from 10 to lactate, myristy lactate, and cetyl lactate. Particularly 40%, optimally from 25 to 35% by weight of the composi preferred are C-C benzoate esters. tion. 5 (2) Alkenyl esters of fatty acids having 10 to 20 carbon Silicone oils may also be included as carriers in the atoms. Examples thereof include oleyl myristate. oley compositions of this invention. These oils may be either Stearate, and oleyl oleate. volatile or nonvolatile. The term "volatile” as used herein (3) -esters such as fatty acid esters of ethoxylated fatty refers to those materials which have a measurable vapor pressure at ambient temperature. Volatile silicone oils are 10 alcohols. preferably chosen from cyclic or linear polydimethylsilox (4) Polyhydric alcohol esters. mono and anes containing from about 3 to about 9, preferably from di-fatty acid esters. diethylene glycol mono- and di-fatty about 4 to about 5, silicon atoms. Cyclomethicone is the acid esters, polyethylene glycol (200-6000) mono- and common name of the preferred volatile silicone oil and is di-fatty acid esters, propylene glycol mono- and di-fatty available as a tetramer or pentamer. Amounts of the volatile 15 acid esters, polypropylene glycol 2000 monooleate. siloxane will range from 10 to 80%, preferably from 20 to polypropylene glycol 2000 monostearate, ethoxylated 70%, optimally from 30 to 65% by weight of the composi propylene glycol monostearate, glyceryl mono- and tion. di-fatty acid esters. polyglycerol poly-fatty esters. ethoxy Linear volatile silicone materials generally have viscosi 20 lated glyceryl monostearate, 1.3-butylene glycol ties less than about 5 centistokes at 25° C. while cyclic monostearate, 13-butylene glycol distearate, polyoxyeth materials typically have viscosities of less than about 10 ylene polyol fatty acid ester, sorbitan fatty acid esters, and centistokes. polyoxyethylene sorbitan fatty acid esters are satisfactory Examples of preferred volatile silicone oils useful herein polyhydric alcohol esters. include: Dow Corning 344. Dow Corning 345 and Dow 25 Corning 200 (manufactured by Dow Corning Corp.); Sili (5) Wax esters such as beeswax, spermaceti, myristyl cone 7207 and Silicone 7158 (manufactured by the Union myristate, steary stearate. Carbide Corp.); SF 1202 (manufactured by General (6) Sterols esters, of which cholesterol fatty acid esters are Electric); and SWS-03314 (manufactured by SWS examples thereof. Silicones. Inc.). 30 Aesthetic properties and stabilization of emulsions incor The nonvolatile silicone oils useful in compositions of porating the Vitamin C may be improved through addition of this invention are exemplified by the polyalkyl siloxanes. a crosslinked non-emulsifying siloxane elastomer. Average polyalklyaryl siloxanes and polyether siloxane copolymers. number molecular weight of these elastomers should be in The essentially nonvolatile polyalkyl siloxanes useful herein excess of 10,000, preferably in excess of 1 million and include, for example, polydimethyl siloxanes with viscosi 35 ties of from about 5 to about 100,000 centistokes at 25° C. optimally will range from 10,000 to 20 million, The term Among the preferred nonvolatile silicones useful in the "non-emulsifying" defines a siloxane from which polyoxy present compositions are the polydimethyl siloxanes having alkylene units are absent. Illustrative of the elastomer is a viscosities from about 10 to about 400 centistokes at 25°C. material with the CTFA name of Crosslinked Stearyl Such polyalkyl siloxanes include the Viscasil series (sold by Methyl-Dimethyl Siloxane Copolymer, available as Gransil General Electric Company) and the Dow Corning 200 series SR-CYC (25-35% active elastomer) from Grant Industries, (sold by Dow Corning Corporation). Polyalkylaryl siloxanes Inc.. Elmwood Park, N.J. Supply of related elastomer may include poly(methylphenyl)siloxanes having viscosities of also be available from the General Electric Company. from about 15 to about 65 centistokes at 25° C. These are Amounts of the elastomer may range from 0.1 to 30%. available. for example, as SF 1075 methylphenyl fluid (sold 45 by General Electric Company) and 556 Cosmetic Grade optimally from 1 to 25%, most preferably from 10 to 20% Fluid (sold by Dow Corning Corporation). Useful polyether by weight of the composition. siloxane copolymers include. for example, a polyoxyalky Minor adjunct ingredients may also be included in cos lene ether copolymer having a viscosity of about 1200 to metic compositions of this invention. These ingredients may 1500 centistokes at 25° C. Such a fluid is available as be selected from preservatives, fragrances, anti-foam agents. SF-1066 organosilicone surfactant (sold by General Electric opacifiers, colorants and mixtures thereof, each in their Company). Cetyl dimethicone copolyol and cetyl dimethi effective amounts to accomplish their respective functions. cone are especially preferred because these materials also The following examples will more fully illustrate the function as emulsifiers and emollients. The former material embodiments of this invention. All parts, percentages and is available from Goldschmidt AG under the trademark Abil 55 proporations referred to herein and in the appended claims EM-90. Amounts of the nonvolatile siloxane may range are by weight unless otherwise indicated. from 0.1 to 40%, preferably from 0.5 to 25% by weight of the composition. Esters may also be incorporated into the cosmetic com positions as pharmaceutically acceptable carriers. Amounts EXAMPLE 1. may range from 0.1 to 50% by weight of the composition. Among the esters are: (1) Alkyl esters of fatty acids having 10 to 20 carbon atoms. Oxidative stability and uniform dispersion of ascorbic Methyl isopropyl, and butyl esters of fatty acids are acid by dimethyl isosorbide was evaluated in the experi useful herein. Examples include hexyl laurate, isohexyl 65 mental and control formulations outlined under Table I. laurate, isohexyl palmitate, isopropyl palmitate. decyl These formulations were examined after two weeks at room oleate, isodecyl oleate, hexadecyl stearate, decyl stearate, temperature and 110° C. 5,750,123 5 6

TABLE I TABLE II Test Formulations Example No. (Weight %) Example No. (Weight 96) COMPONENT 6 7 8 9 10 11 2 COMPONENT 1A 1B C 1D 1E 1F Cyclomethicone 360 36.0 360 40.0 400 45.0 32.0 Gransil SR CYL 24.0 24.0 24.0 20.0 20.0 15.O 27.0 Cyclomethicone 42.0 42.0 42O 420 42.O 420 Butylene Glycol 17.5 - 17.5 - - 29.0 Gransil SR CYL 8.0 18.0 180 180 18.0 18.0 Glycerin - 17.5 - - - - - Polyethylene Glycol 200 20.25 23.25 25.25 28.25 29.25 30.25 10 Polyethylene 10.0 - - 17.5 2.0 10.O. 10.0 Ascorbic Acid 5.0 50 5.0 5.0 5.0 5.0 Glycol 200 Water 4.0 40 40 40 40 4.0 Polyethylene - 10.0 10.0 10.0 120 10.0 - Cetyl Dimethicone Copolyol 0.75 0.75 0.75 0.75 0.75 0.75 Glycol 800 Dimethyl Isosorbide 100 70 5.0 2.0 (0.5 - Dimethyl Isosorbide 2.0 2.0 2.0 4.0 5.0 100 1.0 Results Ascorbic Acid 10 1 0 10 4.0 4.0 5.0 0.5 Ascorbic Acid Retention (%) 15 Cetyl Dimethicone O.8 O.8 O.8 O.8 0.8 - - Copolyol 2Weeks at RJ 97 93 92 83 87 76 Water ba. bal. bal. bal. bal. bal. bal. 2 Weeks at 110° C. 98 93 91 81 87 77

2O The foregoing description and Examples illustrate Essentially no degradation of ascorbic acid occurred in Sele cted embodiments of theh prpresent inventioniny tion and inin lighlight thereof variations and modifications will be suggested to one the presence of 10% dimethyl isosorbide. See Formulation killed in the art, all of which are within th irit and 1A. Formulations 1B through 1E containing dimethyl isos- skilled in neart. o W. are within the spirit an orbide at levels from 7.0% down to 0.5% exhibited a small Purview of this invention. amount of ascorbic acid decomposition. Formulation 1F 25 What is claimed is: serving as a control establishes that in the absence of 1. A cosmetic composition comprising: dimethyl isosorbide there is a v significant drop in Si. ery sig p (i) from 0.1 to 10% by weight of ascorbic acid; (ii) from 0.5 to 10% by weight of dimethyl isosorbide; 30 (iii) from 0.1% to 30% of a cross linked non-emulsifying EXAMPLES 2-5 siloxane elastomer and (iv) a pharmaceutically acceptable carrier present in an A series of further examples were prepared. Their com- 5 effective amount to deliver the ascorbic acid to skin. positions are outlined under Table II. These formulations 2. The composition according to claim 1 wherein the provided good storage stability for the ascorbic acid and carrier comprises a polyol in an amount from 1 to 50% by were judged to be aesthetically consumer acceptable. weight of the composition, 3. The composition according to claim 2 wherein the TABLE 40 polyol is selected from the group consisting of propylene glycol, dipropylene glycol, polypropylene glycol, polyeth Example No. Weight 96 ylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene COMPONENT 2 3 4 5 glycol. 1,3-butylene glycol, 1.2,6-hexanetriol, glycerin, Cyclomethicone 42.0 41.6 400 42.O thethoxylated : glyglycerin, propoxypropoxylated glyglycerin and mixtures Gransi SR CYL 8.O. 17.9 T.3 18.0 45 linereoI. s Propylene Glycol 16.8 14.8 17.5 5.O 4. The composition according to claim 2 wherein the AscorbicPolyethytene Acid Glycol 200 5011.0 5.013.7 5.013.5 5.013.5 polyol.olyol is a mixture of ppolyethylene y y gly col and propy.propylene Diimethyl Isosorbide 2.0 2.0 2.0 2.0 glycol in a weight ratio- of 2:1 to 1:2. s Cetyl Dimethicone Copolyol 0.8 0.8 0.8 O.8 5. The composition according to claim 1 wherein the Water balance balance balance balance 50 carrier comprises water in an amountless than 5% by weight of the composition. 6. The composition according to claim 1 wherein the crosslinked non-emulsifying siloxane elastomer is formed EXAMPLES 6-12 from a divinyl monomer reacting with Si-H linkages of a 55 siloxane backbone. 7. The composition according to claim 1 further compris These series of Examples illustrate the scope of the ing from 10 to 80% of a volatile siloxane. present invention. Various concentrations and different gly col carriers are illustrated. sk k xk xk sk