US 2005O136079A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0136079 A1 Burangulov et al. (43) Pub. Date: Jun. 23, 2005 (54) COSMETIC COMPOSITIONS CONTAINING Related U.S. Application Data FULLERENE CLUSTERS (60) Provisional application No. 60/475,203, filed on May (76) Inventors: Nail Burangulov, St. Petersburg (RU); 30, 2003. Alexander P. Moravsky, Tucson, AZ (US); Yuiya V. Kulikova, St. Publication Classification Petersburg (RU); George I. Dyachuk, St. Petersburg (RU); Raouf O. Loutfy, (51) Int. Cl." .......................... A61K 7/021; A61K 33/44 Tucson, AZ (US) (52) U.S. Cl. ............................. 424/401; 424/125; 424/63 Correspondence Address: SCULLY SCOTT MURPHY & PRESSER, PC (57) ABSTRACT 400 GARDEN CITY PLAZA SUTE 300 The present invention is directed to a cosmetic composition comprising effective amounts of fullerene clusters in asso GARDEN CITY, NY 11530 (US) ciation with cosmetically acceptable carrier to prevent or (21) Appl. No.: 10/858,361 retard free radical oxidation processes in the skin and to the method of using Said composition for reducing damage to (22) Filed: Jun. 1, 2004 healthy Skin or mucous membranes by free radicals. Patent Application Publication Jun. 23, 2005 Sheet 1 of 2 US 2005/0136079 A1 FIGURE 1 Patent Application Publication Jun. 23, 2005 Sheet 2 of 2 US 2005/0136079 A1 Product Raw Material FIGURE 2 US 2005/O136079 A1 Jun. 23, 2005 COSMETIC COMPOSITIONS CONTAINING pure Co and Co fullerenes, higher order-fullerenes, their FULLERENE CLUSTERS mixtures, crystalline Solvates of fullerenes with aromatic molecules, fullerenes adsorbed on graphite, etc. CROSS REFERENCE TO RELATED 0007. The high strength of the fullerene molecular crys APPLICATIONS tals results in their drastically different chemical and bio 0001. This application is claiming priority under 35 chemical behavior compared to that of Separate fullerene U.S.C. Sl 19(e) of U.S. Provisional Patent Application No. molecules, Such as those in true Solutions and prevents the fullerene molecule per Se from being used in cosmetic, 60/475,203 filed on May 30, 2003. pharmaceutical or Veterinary compositions. For example, the macroscopic size of a fullerene crystal does not allow its FIELD OF THE INVENTION incorporation in Skin tissues and other biological Structures. 0002 This invention relates to ultrafine dispersed Only the surface molecules, accounting for about 0.4% of all fullerene particles and their use in cosmetics. molecules in a common micrometer-Size fullerene particle, are exposed to Solution and thus allowed to react with BACKGROUND OF THE INVENTION Solution components. Moreover, the Specific reactivity of Surface fullerene molecules is generally much lower than 0003) A fullerene is a third allotrope of carbon which is that of individual dissolved molecules. different from other forms of carbon, Such as diamond and graphite. It consists Solely of carbon atoms arranged in a 0008. There are only a limited number of solvents hollow closed cage. More Specifically, a fullerene is com capable of dissolving fullerenes. Aromatic Solvents and prised of closed polyhedra in which the carbon atoms are So halogenated hydrocarbons, traditionally used for dissolving arranged that they are linked together to form hexagons and fullerenes, are Strong toxins, thereby precluding their use in pentagons. Stable fullerenes used in the present invention cosmetology and pharmaceutical and Veterinary composi are produced in industrial or laboratory Scale amounts. tions. Examples include Co, C7o, C76, C7s, Cso, Cs2, Cs, and 0009. Designers of cosmetics and medicinal drugs are higher molecular weight molecules. trying to take advantage of various fullerene properties to overcome the difficulties of using fullerenes outlined here 0004 Fullerenes were first described in an article by inabove. The use of crystalline fullerenes in oil-in-water or Kroto et al., in Nature, vol. 318, p. 163 (1985), in which their water-in-oil emulsions, Suspensions, powders, tinted existence was postulated based upon mass-spectra of the creams, nail varnishes and other cosmetic compositions was products of laser vaporization of graphite. Fullerene, as a described in U.S. Pat. No. 5,612,021 to Melull “Cosmetic Substance, was made available in 1990, when Huffman and Make-Up Composition Containing Fullerene or Mixture of Kratschmer found a method to prepare and isolate Fullerenes as a Pigmenting Agent”. Fullerenes are used in fullerenes, Such as Co and Co in macroscopic amounts. See these make-up compositions exclusively as a pigment or Kratschmer et al., Nature, vol. 347, 354 (1990). filler to allegedly endow these products with a certain color, 0005 The geometry and electronic structures of as well as other useful cosmetic properties Such as good fullerenes impart to them unique physical properties and covering power and pleasant application characteristics. The chemical reactivities. For example, the electron affinity of crystalline fullerene obtained by a Standard Synthetic pro fullerenes is high. For example, Co has an electron affinity cedure, as referenced in U.S. Pat. No. 5,612,021, does not of 2.65 eV. They possess enhanced reactivity towards the possess the important properties of dissolved fullerene mol addition of free radicals to carbon-carbon double bonds and ecules. It has impeded access to living tissues, active centers towards nucleophilic attack by lone pair electrons. Addition of enzymes and other molecular biological objects, and it of free radicals to fullerene double bonds causes formation cannot pass through the cellular membranes to take part in of rather inactive fullerene-centered radicals that are unable biochemical processes of interest for cosmetics. Thus, U.S. to participate in free radical chain propagation reactions, for Pat. No. 5,612,0211 essentially utilizes only the high optical example, in free radical oxidation of organic compounds. density of the fullerene pigment, and fails to disclose the use Thus fullerenes are antioxidants. It has been Stated that one of a fullerene as a biologically active component in cosmet fullerene molecule is capable of inactivating Some tens of CS. “hot” free radicals by sacrificing double bonds. Furthermore, 0010. However, derivatives of fullerenes were shown to the fullerene molecules can catalytically Scavenge and have biomedical applications. Chiang, et al. in U.S. Pat. Nos. recombine free radicals, due to the occurrence of reductive 5,994,410 and 5,648,523 disclose chemical derivatives of elimination of the attached organic groups from the fullerene fullerenes useful as free radical Scavengers and the use cage in the form of appropriate dimers. This property thereof for treating free radical related medical conditions. imparts to a fullerene molecule a capability to convert free Although the addition of functional groups to the fullerene radicals into inactive molecular products. molecules imparts the necessary Solubility to the fullerene 0006 The unique properties of fullerenes create peculiar derivatives, the preparation of these derivatives inevitably physical and chemical features of fullerene Solids. For results in a reduced number of double bonds and concomi example, the fullerene molecular crystal has an exceedingly tant decrease in the ability of the fullerene molecules to high energy of intermolecular interaction, much greater than Scavenge free radicals. Moreover, functional groups create that of molecular crystals of the majority of Similar size Steric hindrances for interaction of fullerene cage double organic Substances. This is attributable to the extended bonds with free radicals in Solution, thus further decreasing conjugated electronic structure of the fullerene cage, and the Specific reactivity of the fullerene. dense mode of fullerene molecules packing in the lattice of 0011 Heretofore, no one has been successful in making molecular crystals. This phenomenon is seen in crystals of a fullerene exhibiting pharmacological or biological activity US 2005/O136079 A1 Jun. 23, 2005 without the addition of functional groups to the fullerene 0018 FIG. 2 is a schematic of the laboratory scale cage. However, the present inventors have found a means of electrohydraulic impact chamber employed for fractionation dissolving fullerenes in non-toxic bio-compatible Solvents of fullerite powder into the nanosize fullerene clusters. The without performing preliminary chemical derivatization of chamber is filled to capacity with water and has the shape of the fullerene moiety. They have found a way to maximize an ellipsoid for rotation. Electric discharge through water is the useful chemical and biochemical reactivity of fullerenes. effected between two tungsten electrodes in a focal point of More specifically, they have found a method for solubilizing this ellipsoid, and the fullerite Sample is positioned in fullerenes by converting them into Small molecular clusters, another focus to be treated with the cumulative shock wave. and Subsequently using the Solubilized clusters in cosmetic The fullerite is suspended in a liquid inside a thin-walled compositions. This takes advantage of the enhanced chemi plastic cell and thus Separated from the Outer-cell shock cal reactivity of fullerene molecules and their Small aggre wave transmitting water medium. Alternatively, the fullerite gates and the concomitant higher positive biological activity Suspension is continuously circulated in a closed contour, of interest for Skin care and other cosmetic applications. which includes