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 a thin-walled plastic tube passing through the focal point. The liquid for Suspending the fullerite is SUMMARY OF THE INVENTION chosen from water, alcohols, natural oils, etc. 0012. Accordingly, the present invention is directed DETAILED DESCRIPTION OF THE towards a cosmetic composition comprising a cosmetically INVENTION effective amount of fullerene clusters in association with a cosmetic carrier. 0019 AS used herein, the term “mammals” refers to any member of the class mammalia, including but not limited to, 0013 Another aspect of the present invention is directed humans, dogs, cats, horses, pigs, cow, and the like. The towards a method of preventing or reducing damage to preferred mammal is human. healthy skin or mucous membrane of a mammal especially humans, by free radicals which comprises applying to the 0020 Herein the term “cluster” has the general meaning healthy skin or mucous membrane a cosmetic composition defined in the chemical literature. A molecular cluster of comprising a cosmetically effective amount of fullerene fullerenes is a small assembly of fullerene molecules held clusters. together by Van der Waals forces. The size of this assembly may vary from a few fullerene molecules to about a billion. 0.014) Another aspect of the present invention is directed The internal structure of clusters is presumably close to that to a method of deactivating toxins in the skin or mucous found in molecular crystals of fullerenes. Various shapes of membrane of mammals, especially humans, which method clusters are conceivable, depending on cluster size and comprises applying an effective amount of fullerene clus interaction with its environment. Clusters can be directly ters, in accordance with the present invention, to the skin of Solvated by the Solvent molecules, thus forming non-ideal Said mammal. Solutions of fullerenes, close in nature to stable Sols and 0.015 Yet another aspect of the present invention is Suspensions. Clusters can form donor-acceptor complexes directed to a method of treating antimicrobial or antiviral with certain organic molecules (ligands), which are Soluble infection of skin and mucous membranes of a mammal by in polar Solvents of interest and thus may impart fullerenes administering to the skin of Said mammal an effective with solubility in these solvents as well. Both directly amount of fullerene clusters in the presence of Solar light. Solvated and complexed fullerene clusters are utilized in the present invention. 0016 A still further aspect of the present invention is related to a method of human skin and mucous membrane 0021. The fullerene clusters described herein are pre protection against intense Visible and UV irradiation, e.g. to pared from fullerites (solid fullerenes). Examples of fuller prevent Solar burns, by administering to the Skin an effective ites include Solid forms of pure or mixed molecules Co, Co, amount of fullerene cluster. Cs, Co, and the like, that may incorporate crystallization Solvents. BRIEF DESCRIPTION OF THE DRAWINGS 0022 Fullerites or solutions or suspensions containing 0017 FIG. 1 presents a space model of a hydrated Same are used as Starting material for making the fullerene fullerene molecule Co(H2O)so designed by Professor Mar clusters of the present invention. Preferred fullerenes for this tin Chaplin. The intact fullerene molecule (gray fused purpose are Co and Co. The fullerenes are prepared in spheres for carbon atoms) is encased in the cavity formed by accordance with procedures known to one of ordinary skill 80 water molecules, each water molecule being represented in the art. For example, the fullerenes can be prepared by the by a black Sphere for an oxygen atom and two light gray methods described in Kratschmer, et al., Nature 347, 354 Spheres for hydrogen atoms. The cavity was formed by the (1990), U.S. Pat. No. 5.273,729 to Howard, et al., U.S. Pat. withdrawal of a dodecahedron water cluster (H2O)o from No. 5,876,684 to Withers, et al., U.S. Pat. No. 5,227,038 to the water icosahedron (H2O)oo. It is seen that directly over Smalley, et al., U.S. Pat. No. 5,300,203 to Smalley; and U.S. each fullerene hexagon a hydrogen atom from a water Pat. No. 5,556,517 to Smalley, U.S. Pat. No. 6,083,469 to molecule is positioned, thus forming 20 hydrogen bonds Leftin, and U.S. Pat. No. 6,077.401 to Fields, et al., the between oxygen atoms and the pi-systems of the corre contents of all of which are incorporated by reference. sponding benzenoid rings. The accidental geometry corre 0023. As used herein, the term “fullerene' refers to a spondence results in unperturbed positioning of the inner 20 molecule containing an even number of carbon atoms water molecules as well as the outer 60 molecules relative to arranged in a closed hollow cage. Fullerenes may contain original icosahedron Structure, and therefore, an enhanced even numbers of carbon atoms totaling from 20 to 500 or energy Stabilization for Co(H2O)so. more. Fullerenes are not necessarily Spherical. They may US 2005/O136079 A1 Jun. 23, 2005

take the form of long tubular Structures with hemispherical mixture of more than one type of fullerene. A Separate caps at each end of the tube. Hyperfullerene Structures also Solution of the water Soluble polymer(s) and/or porphyrin(s) exist wherein one Structure is contained within a Second is prepared in an appropriate organic Solvent, Such as larger Structure. For generally Spherical molecular struc chloroform, methylene chloride, ether or the like. The tures, their hyperfullerenes resemble an onion layered Struc fullerene and ligand Solutions are mixed in the argon gas ture. Tubular Structures within larger Structures are also filled reactor for a time Sufficient for a reaction to proceed. possible. Fullerenes are more fully described in the litera For example, this may take from 30 minutes to one day, ture. Examples of fullerenes include Co, C7o, C7, Cs, Cs, depending on the reagent concentration and the reaction Coe, Co, Cso, Czo and the like. It is preferred that the temperature, which can range from about room temperature fullerene has at least 60 carbon atoms. The preferred to the reflux temperature of the solvent mixture. The weight fullerenes are Co and C7o. ratio of fullerene and polymer ranges from about 1:10 to about 1:10,000, more preferably from about 1:25 to about 0024. The fullerene clusters contemplated by the present 1:250, and most preferably from about 1:50 to about 1:150; invention may contain 1 type of fullerene or more than one while the fullerene/porphyrin molar ratio ranges from about type of fullerene. It is preferred that it contains 1 type of 1 to about 10, depending on the reagents and Solvents chosen fullerene. For example, it may contain Co or C7o or a for the Synthesis, and on the desired composition of the mixture thereof, although it is preferred that it only contains resulting complex. A colored product, e.g., a brown product, one type of fullerene, either Co or Co. as in the case of PVP, is formed, indicative of the formation 0.025 AS described herein, the present invention is of the water soluble fullerene/ligand complex. After the directed to making and using fullerenes in the form of reaction is over, the Solvent is removed under vacuum, at molecular clusters. The formation of molecular clusters is about room temperature or slightly higher, for example, up exemplified by two methods. to about 50° C. 0026. In one method, the fullerites are mechanically 0030. After the solvent is removed, the cosmetic vehicle, disintegrated into Separate Small agglomerates of fullerene e.g. water, alcohol, or more preferably a phosphate buffer molecules (clusters). This is based on the mechanical frac with a pH of about 7.4 is added to the flask in sufficient tionation of fullerite effected by hydraulic impact in various amounts to dissolve the fullerene cluster and to form a liquids, including water, alcohols, natural and Synthetic oils, solution. The dissolution of the fullerene complex in the and the like. vehicle may be accelerated through the use of heating, stirring, ultrasonic treatment or any other means known to 0027. The other method consists of solubilizing the one of ordinary skill in the art. The preferred method is fullerene Solids in a liquid by complexing the fullerene 15-40 kHz and more preferably 20-40 kHz ultrasonic treat clusters with water Soluble polymers and/or porphyrins. In ment at an intensity of about 15-50 W/cm and more this case, the Soluble complexes of fullerenes with polymers preferably 20-50 W/cm' for about 30 to about 600 seconds, and/or porphyrins are shown to predominantly contain and more preferably for about 30 to 300 seconds. fullerenes in the form of Small molecular clusters associated with polymer and porphyrin molecules as ligands. Examples 0031 Optionally and preferably, the aqueous fullerene of water soluble polymers useful in the formation of Solution is filtered to remove impurities. Also, the fullerene fullerene clusters using this method include polyvinylpyr Solution may be concentrated to a predetermined level by rolidone (PVP), polyethylene glycol (PEG), polypropyle reducing the Solvent Volume by evaporation. neglycol (PPG), copolymers of vinyl pyrrolidine, ethylene 0032) Another method of forming the fullerene clusters is glycol, propylene glycol, and the like. by mechanical dispersion of the fullerite (solid fullerene or a solid mixture of fullerenes) by subjecting the fullerite to 0028. The water soluble polymers and the porphyrins are mechanochemical treatment. This treatment is effected in a not chemically bound to the fullerenes by Strong covalent liquid medium to split the fullerene to nanosize clusters. bonds; instead they interact via Van der Waals forces The Preferably, the fullerites are reduced to the size of about 5 to donor-acceptor bonding between the ligands and fullerene about 50 nm and more preferably from about 5 to about 15 cluster in the complex does not significantly disturb the nm. Any method known to one of ordinary skill in the art can fullerene molecule electronic structure, i.e. all of the carbon be used to convert the fullerite to nanosize clusters. carbon double bonds of the fullerene cage are intact. More Examples include electrohydraulic impact, ultrasonic- and over, the donor-acceptor bonding has a reversible character acoustic wave treatments, in the power range from about ensuring both the delivery of a molecular cluster to the cell 0.01 to about 100 kW. The preferred method is electrohy membrane through a water phase and the release of a Single draulic (EH) impact, as it generally produces Smaller clus hydrated fullerene molecule that is capable of permeating ters having greater efficiency. the membrane. Since the carbon-carbon double bonds 0033. The essence of the EH effect consists of the pro remain essentially intact and there are no Steric hindrances duction of high magnitude and gradient local dynamic invoked by functional group, the fullerene molecule thus hydraulic pressure during the pulse of a high Voltage electric delivered into tissues retains high chemical reactivity, which discharge inside a liquid. This kind of dynamic pressure is provides for the high biochemical activity of water soluble efficient at cracking Solids, and thus forms fine dispersions fullerene clusters, in particular, to act as antioxidants. of Solids in the liquid. Examples of an apparatus that may be 0029. An exemplary procedure for preparing the water useful for disasSociating fullerenes by EH impact are Soluble fullerene complex with polymer and/or porphyrin described, for example, in U.S. Pat. Nos. 6,254,764 to ligands is outlined below. The fullerenes are dissolved in a Babington, et al., 5,868,919 to Babington, et al. and 4,917, non-polar organic Solvent, Such as benzene, toluene, or the 785 to Juvan, et al., the contents of all of which are like. The fullerene Solution may contain one type or a incorporated by reference. US 2005/O136079 A1 Jun. 23, 2005

0034. There are several advantages of the EH effect capable of producing Secondary Shock waves, which are still technology for comminution of fullerites. powerful enough to demolish Solid particles Suspended in 0035. When electrical energy is suddenly released into a water. The implosion of a bubble formed near a solid surface liquid in the form of a Spark discharge between two elec is asymmetric, So that a jet of liqiuid about 10 micrometers trodes, an intense mechanical shock wave propagating at in diameter and 50 micrometers in length is expelled from SuperSonic velocity is created. The Shock wave consists of the collapsing cavity. This jet moves toward the Surface at two Zones. The Steep leading edge of the Shock wave roughly 100 meters per Second. The microjets impinge onto represents the compression Zone, which is followed by the the fullerite Surface and cause fullerite particle fragmenta rarefaction Zone, where the pressure falls off from its peak tion. This proceSS produces fragments commenSurate with value to a Small negative value and then returns to its the jet size, that is, in the micrometer range, but it is most pre-Shock value. The rarefaction Zone is travelling faster likely incapable of producing nanometer size particles. This than the compression Zone and the entire Shock wave is further supported by the fact that cavitation bubbles of the gradually decreases in amplitude as it travels. Both Zones Same nature and function are produced in ultraSonic treat perform the work on distortion of a solid particle met by the ment of fullerite Suspensions, and the characteristic size of Shock wave in the liquid. The distortion can eventually lead particles produced is appreciably larger than that obtained to particle fracture, depending on particle mechanical prop during EH impact treatment, with Similar energy input into erties and shock wave parameters. When a shock wave the liquid in both methods. enters a Solid body it causes dilatational or longitudinal 0038. Thus, the EH technique has important advantages StreSS and Shear or transverse StreSS. The StreSS a is linearly over more common ultraSonic and acoustic wave treatments, related to the density of the solid p, the wave velocity C and rendering it preferable for producing nanosize clusters of the Solid particle element Velocity V through the equation: fullerenes. It can be easily Scaled up. Facile control of key O=pCV. This relationship applies to both longitudinal and features of EH proceSS is ensured in very wide range of Shear waves. The shock wave Velocity at EH impact caused parameters. Moreover, the magnitude of many parameters by electric discharge could reach about 18 km/s, which important for the fractionation process are achieved by this exceeds the velocity of sound in water (~1.5 km/s) by an EH technique but inaccessible in other methods, as can be order of magnitude. It also is much larger than the Velocity inferred from the following listing of EH shock wave of shock waves (~2 km/s) generated by implosion of cavi properties and EH devices features: tation microbubbles during ultraSonic treatment of water. Accordingly, the magnitude of stresses developed during EH 0039) Typical shock wave front rise time-10-100 impact greatly exceeds that from ultrasonic treatment. S Therefore, the EH impact is much more effective in com 0040 Total pulse duration-100 ns-10 its minution of fullerite particles Suspended in water, compared to other treatments capable of generating Shock waves of 0041) Maximum pressure in the hot plasma chan lower velocity. nel-1-3 GPa. 0042 Typical positive peak pressure on the 0036) As the tensile strength of fullerite is much less than the compression Strength, the disintegration of fullerite sample-100 MPa. particles is likely to occur mainly in the rarefaction Zone of 0043. Typical negative peak pressure on the sample a shock wave, terminating with the So called tensile or -1-10 MPa. negative phase of a shock wave. A negative peak pressure up to 10 MPa and of a total duration of a few microseconds is 0044) Maximum temperature in the hot plasma developed in the tensile phase of a shock wave in water. This channel-15,000-40,000 K tensile load is transmitted over the fullerite particle, causing 0045. Maximum initial shock wave velocity-10-18 it to crack along the plane parallel to the dilatational wave km/s front. The distortion of a fullerite particle due to the shear Strain Splits the particle in normal to dilatational wave 0046l Pulse energv–0.5gy CU’=-1-100 kJ direction. This process significantly contributes to particle 0047 Specific energy per pulse-5 J/cm of liquid fragmentation, as the shear Strength of fullerite is low while in typical fractionation reactor the transverse wave Velocity is comparable to that of the longitudinal wave. 0048 Specific power in the pulse-2 MW/cm of liquid 0037. These main fragmentation processes are comple mented by fullerite particle fragmentation caused by Sec 0049 Efficiency of conversion of electrical energy ondary Shock waves and liquid microjets produced by the into mechanical--50% collapse of cavitation bubbles. This fullerite particle frag 0050 Discharge capacitor voltage-3-100 kV mentation caused by Secondary Shock waves and liquid microjets generally cannot form the Smaller particle sizes 0051) Pulse discharge current-10-1000 kA found in the fullerene clusters. When the peak amplitude of Electrical capacity-3-1000 pF the negative preSSure in the tensile phase of a shock wave 0052 exceeds about 1 MPa, transient cavitation bubbles of about 0053) Inductance of discharge circuit-5-50 nH 100 micrometer in diameter are induced in water. The 0054 Practical rate of pulse repetition-0.2-20 collapse or implosion of cavitation microbubbles takes leSS pulse/S than a microSecond and causes the gas pressure and tem perature inside the cavity to jump to about 150 MPa and 0055. No impurities are introduced into the product 5,500 C, correspondingly. Hotspots that are thus created are in the EH apparatus. US 2005/O136079 A1 Jun. 23, 2005

0056. For the sake of comparison, some features of metic vehicles, and the like. However, as previously Stated, ultraSonic treatment technique are presented below: the more preferred method of forming fullerene clusters is 0057 Typical compression wave rise time-50 its best accomplished by the EH technique. 0058 Maximum positive peak pressure on the 0083. The data on the structure of fullerene clusters is sample-5 MPa (Typical 1-2 MPa) Scarce. Without being bound to a particular hypothesis or instrumental observation, the probable structure of clusters 0059 Maximum negative peak pressure on the and composition of Solutions obtained can be presented as sample-5 MPa (Typical 1-2 MPa) follows. Microcrystalline fullerite is mechanically loose and 0060 Frequency of compression-dilatation cycles becomes disintegrated into nanosize clusters when adequate 20-40 kHZ tensile or shear Strain is applied. Appropriately prepared fullerene clusters do not precipitate from water or any other 0061 Ultrasound wave velocity in water-1.5 km/s liquid Solution of interest for a period generally exceeding several months. The reason for this stability is not yet 0062) Cavitation bubble diameter-60-200 um definitively established, and may be different in different 0063) Cavitation bubble growth time-100-400 us Solvents. 0.064 Cavitation bubble collapse time-100 ns-1 us 0084. The water soluble polymer(s) and/or porphyrin(s) 0065. Gas pressure in the collapsed cavitation stabilize the fullerene clusters. Without wishing to be bound, bubble-150 MPa. it is believed that the stability can be explained as follows. Fullerene clusters, having Sizes as Small as individual mol 0066 Gas temperature in the collapsed cavitation ecules, have attractive interactions with electron-donating bubble-5,000 K groups of polymers and/or porphyrins, and thus form a 0067 Liquid temperature near collapsed bubble complex which is soluble in water and other solvents due to 2,100 K the presence of polar groups of the polymer and/or porphy rin that presumably do not bond to the fullerene. Formation 0068. Efficiency of conversion of electrical energy of Such complexes has been confirmed by Spectral tech into mechanical--50% niques. Occurrence of fullerenes in cluster form in these 0069 Yield of OH radicals G-1x10' mol/J; Num complexes is Supported from the appearance of absorption ber of OH radicals produced-1x10"/cycle bands in their electronic spectra in the visible range that are characteristic of fullerene molecules in close Van der Waals 0070 Continuous power input-50 W-5 kW contact to each other. This characteristic absorption gener 0071 Surface density of power input-1-100 W/cm ally is more pronounced in the Short-wave region of the Visible range. Moreover, it imparts to Solutions of fullerene 0072 Specific power for continuous treatment-1- cluster complexes a color that is different than would be 100 W/cm of liquid present if the fullerene were dissolved in solution. For 0.073 Some physical properties of solid fullerite Co are example, a Solution of fullerene 60 cluster complexes have presented below to enable assessment of its behavior under a yellow to brown coloration, instead of the violet color of conditions of the EH and ultrasonic treatments: true Solutions of fullerene Co containing separate mol ecules. 0074) Mass density—1.72 g/cm 0085 Similar spectral features and color changes are 0075 Bulk modulus-14 GPa. intrinsic to fullerene, e.g., Co, Solutions in unsaturated fatty 0076 Longitudinal velocity of Sound-3.6 km/s acids and natural and Synthetic oils that contain double C=C bonds in their structure. This indicates the occurrence 0077 Transversal velocity of sound 2.1 km/s of fullerene Co in the cluster form in these Solvents as well. 0078. Thermal conductivity (300 K-0.4W/mK 0086) Without wishing to be bound, it is believed that the 0079) Phonon mean free path-5.0 nm Strong polarizablility of fullerenes, Such as Co, coupled with the polarizable double C=C bonds in ligands, is (one Compressibility (-dV/dP)-6.9x10' cm / considered to be responsible for the enhanced attraction yn between ligands and fullerene clusters, which results in the formation of a Soluble complex. This complex prevents 0081 Volume coefficient of thermal expansion aggregation of clusters and thus precipitation of Solid 6.2x10 cm/K fullerenes, e.g., Co, from the Solution. The Solubility of 0082 It is clear from the data above that the EH tech fullerenes in natural oils reaches dozens of milligrams per nique is more efficient in fractionating the Solid fullerite than milliliter, and thus exceeds the Solubility in common aro ultraSonic treatment, and in particular more energy efficient matic Solvents that are among the best Solvents for and productive. However, ultrasonic treatment of great dura fullerenes. The interaction of fullerene molecules with mol tion can also provide fullerene clusters in the form of stable ecules of natural oils and aromatic Solvents is realized colloidal solutions, which could be barely distinguished mainly through the polarization forces described herein visually from the product of EH technique. Therefore, above. It is reasonable to assume that the total Strength of ultraSonic treatment is another method for fullerene cluster this interaction, and hence the Solubility value, would be production, as it can be efficiently employed in auxiliary roughly proportional to the number of double C=C bonds operations Such as re-dispersion of the dried fullerene cluster present in the Solvent and available in contact with fullerene product in liquids, mixing of fullerene clusters with coS molecule. AS this number is much higher for an aromatic US 2005/O136079 A1 Jun. 23, 2005

Solvent than for a natural oil, the Solubility in an aromatic 0091. There are experimental observations that confirm Solvent should be much higher as well. Since the opposite that fullerene clusters exist in a dynamic equilibrium with occurs, this can be considered an indication that fullerene hydrated Single fullerene moieties. The thus produced Solutions in natural oils are actually stable Sols of fullerene hydrated fullerene molecules could be either fullerols or clusters rather than true Solutions. intact fullerene cages. The existence of the latter has been postulated in the literature, and a molecular model for the 0087. The stability of fullerene clusters in pure water is Solvation of an intact fullerene cage Such as Co. by water different. Without wishing to be bound, it is believed that molecules has been designed (FIG. 1). Water in the liquid negatively charged fullerene clusters dominate in water State possesses a virtual crystalline Structure. In the molecu Solution. The most likely reason for the appearance of lar model, the Co fullerene is located inside a hollow negative charge Seems to be dissociation of hydroxyl groups icosahedron composed of 80 water molecules. The inner covalently bound to the fullerene cage. The acidity of these twenty water molecules are ideally situated to form OH. . . hydroxyl groups is likely much higher than in water mol p hydrogen bonds with each of the twenty 6-membered rings ecules because of the extremely high electron affinity of the in the fullerene Co., by positioning directly over these rings, fullerene molecule(e.g., 2.65 eV for Co., the Smallest which is the optimum position for a hydrogen bond with a fullerene). This ensures facile release of protons into water benzene molecule. These 20 water molecules are linked in pH ranges down to about 3, and the concomitant forma through the 60 fully hydrogen bonded water molecules from tion of negatively charged particles. The attached hydroxyl the outer shell of the icosahedron. It is also believed that the groups originate from the attack of hydroxyl radicals on the stability of hydrated low-order fullerols would also benefit double bonds of a fullerene. from this fairly unique Structural coincidence of the cavity 0088. The main source of hydroxyl radicals in water and fullerene molecule. Solutions is the collapse of cavitation bubbles produced 0092. Without wishing to be bound, it is believed that the during ultraSonic treatment or Shock wave passage. The rate hydrated Single-cage low-order fullerols and hydrated pris constant for the reaction of hydroxyl radicals with organic tine fullerene molecules penetrate the cell membranes and molecules, including compounds with double C=C bonds, take part in the cell metabolism, while larger fullerene is close to the diffusion-controlled value; therefore, for clusters are deemed merely responsible for fullerene bio example, ultrasonic treatment is used in water purification chemical activity outside of the cell. The equilibrium co Systems to get rid of trace amounts of phenols and other existence of these soluble forms of fullerenes can be used for organic contaminants. The reaction should be very efficient the rationalization of a variety of known useful functions of in the case of fullerene clusters as well, thus providing the fullerenes in cosmetic applications, and constitute a basis for fullerene molecules at the Surface of clusters with Some designing new cosmetic Systems. hydroxyl groups. 0093. The clusters of fullerenes formed herein may be 0089. These few ionogenic hydroxyl groups are neces placed in aqueous Solutions or organic Solvents Such as Sary to create a double electric layer at the Surface of a alcohols and oils. For the EH dispersion and ultrasonic fullerene cluster and thus stabilize the colloid particles dispersion of fullerene-containing Substances with the pur against coalescence. The quantity of hydroxyl groups pose of Subsequent use in cosmetic products, the most present can vary depending on the cluster Size and the pH of appropriate Solvents are water or alcohol Such as alcohol the medium, and may be too small to be detected. Never containing 1-6 carbon atoms as well as natural and Synthetic theless, there exists an instrumental technique capable of oils. A natural oil, as defined herein, is a complex mixture of revealing the presence of Such Small quantities of hydroxyl various natural compounds with one or Several double groupS. Specifically, a broad light absorption is developed bonds, and C=O and C-OH groups. Preferably these are near the 450 nm wavelength in the Spectra of fullerene e.g., polyunsaturated fatty acids-from about 16 to about 38 Co, Solubilized in water by ultrasonic or by EH impact carbon atoms. The flexibility of hydrocarbon fragments treatment. It is generally attributed to the disturbance of located between functional groups in the polyunsaturated fullerene molecule electronic Structure, caused by attach fatty acids enables Simultaneous donor-acceptor type inter ment of functional groups, in particular, hydroxyl groups. action of Several of their functional groups of the polyun This absorption at 450 nm is commonly much more intense Saturated fatty acids with a fullerene cluster, which interac than what could be expected from that originating from tion is responsible for the high solubility of fullerences in inter-fullerene Van der Waals interactions described above oils. To prevent excessive formation of free radicals during for the case of fullerene cluster complexes with various EH and ultraSonic dispersion treatments of fullerites in oils, non-covalently bound ligands. The enhanced absorption at the applied power density should be reduced to approxi 450 mm thus provides additional evidence that fullerene mately one half of the optimal value for water and alcohol clusters with hydroxylated fullerene molecules (fullerols) at liquid media. For example, the ultraSonic dispersion treat their Surface are formed. ment at 10-18 W/cm power density level is optimal for dissolution of fullerites in various oils, and does not cause 0090. In this structural model, without wishing to be either deterioration of oil quality or chemical bonding of the bound, it is presumed that the inner fullerene molecules in polyunsaturated fatty acid molecules to fullerenes. The the cluster are largely intact and held together by inter fullerene cluster Solutions thus obtained in oils can be used fullerene Van der Waals forces. However, the incorporation for preparation of cosmetic compositions without further of Some low-order fullerols into the cluster inner Space is purification. also possible, as fullerols can also form crystalline Van der Waals structures. Without wishing to be bound, it is believed 0094. The fullerene clusters in the composition of the that the fullerene clusters So Structured could be transported present invention may be associated with water Soluble through the intercellular medium to the cell membrane. polymers and/or porphyrins. Examples of water Soluble US 2005/O136079 A1 Jun. 23, 2005

polymers that can associate with the fullerene clusters present in these Solutions in cluster form. That is, fullerenes include polyvinyl pyrrolidone, polyethylene glycol, are Solubilized as clusters in these terpene Solvents and polypropylene glycol, copolymers of vinyl pyrrolidone, eth eventually in the cream or ointment or rouge, or whatever ylene glycol, propylene glycol and the like. Alternatively, or other fullerene cosmetics is utilized. The fullerenes therein in combination with the polymers and/or water soluble are clusterS Suspended in the terpene Solvent in a form close polymers, the fullerene cluster of the present invention may in essence to a (nano) colloidal Solution. be associated with a terpene. 0106 Solubilized terpenes (fullerene clusters) can be 0.095 Terpenes, are chemical compounds of the simplest easily incorporated into a cream or other cosmetic means by formula CoHo. However it is problemed that the terpene is general operations well known in the art to obtain cosmetics an unsaturated unsaturated acryclic and cyclic hydrocarbon with excellent quality. of the formula (CSH), where n>2. Terpene are components of ether oils. Terepenes are natural hydrocarbons and are 0107 The commentary herein regarding fullerene clus contained in plants. Terpenes are composed of isoprene ters in association with oils and unsaturated acids is equally units. Isoprene (2-methylbutadiene-1,3), CH=C(CH)- applicable to terpene. CH=CH, is a component of Such natural Substances as 0108. The fullerene clusters in the present composition caroteniodes (e.g., f-caroteine) and phythol, a part of chlo are combined with cosmetically useful materials to form rophyll. The ether oils, for example, camphor oil, contain not cosmetic compositions. Cosmetically useful materials only terpenes, but also terpenes derivatives (alcohols, alde include, but are not limited to, antioxidants, binders, bulking hydes, ketones, esters and ethers). agents, chelating agents, colorants, emolients, emulsion 0.096 Terpenes are capable of dissolving appreciable Stabilizers, film formers, fillers, fragrance components, gel amounts of fullerenes. For example, the Solubility of Co in ling agents, hair conditioning agents, hair fixitives, humec terpenes or the aforementioned derivatives varies in the tants, plasticizers, preservatives, skin conditioning agents, range from about 3 to about 20 mg/ml. The dissolution of Solvents, SunScreen agents, Surfactants, ultraViolet light fullerenes in terpenes is facilitated by implementing the absorbers, Viscosity controlling agents and waxes. Various Same physical activation means, which are described herein other cosmetically useful materials can be found in the for “dissolution of fullerenes in water, oils, and unsaturated CTFS Cosmetic Ingredient Handbook, J. M. Nikitakis, Ed., acids. These means include, among others, ultrasonic treat 1 Edition, pages 51-101 (1988), the disclosure of which is ment and electrohydraulic impact technique being applied to hereby incorporated by reference. the mixture of fullerene and liquid terpenes, as well as common Supplementary treatments, including elevated tem 0109 Cosmetic compositions of the invention include perature, Stirring, maceration, ketones attrition milling, and compositions that may contain a wax. the like. 0110. The fullerene clusters prepared in accordance with 0097 Terpene derivatives such as alcohols, aldehydes, the present invention are associated with a cosmetically and lower alkyl (C-C) esters leave alkyl (C-C) ethers or acceptable carrier. The vehicle may be an aqueous Solution, acids of terpene may also be associated with the fullerene e.g. water, or a polar organic Solvent, alcohol, e.g. ethanol or clusters. The terpenes as well as the terpene moiety in the another polar-Solvent; a natural or Synthetic oil, an oil-in derivative contain at least 10 carbon atoms wherein m is at water emulsion; or a water-in-oil emulsion; or a wax, and the least 1, and is preferably no more than 100 and more like. The carrier should obviously be non-toxic. The pre preferably not more than 10, and most preferably is 1. ferred carrier of the compositions of the present invention is Examples include an aqueous Solvent. 0.098 Geraniol, CH,OH (alcohol with the scent 0111 Depending upon its function, the cosmetic compo of roses), Sitions of the present invention may be provided in various forms, Such as Solutions (lotion type compositions), thick 0099 Citrinellol, CHOH (alcohol with a tender ened Solutions, gels, ointments, emulsions (cream, milks), Scent of roses), vesicular dispersions, powders, dense powders, pastes or 0100 Citrel, CHCCHO (aldehyde with lemon Solid agents. More specifically, the cosmetic compositions of fragrance), the present invention may be dispersed in various forms, including, but not limited to, blushers, creams (including 0101 Linallyl acetate, CHCOOCoH (ester with face creams, hand creams, moisturizing creams and Sun lavenda scent), Screen creams), cream powders, eye liners, eye shadows, 0102 Menthol, CHOH, (with mint scent) eyebrow pencils, foundations, lotions, mascaras, micro emulsions, ointments, pomades and rouges. They may also 0103) Terpineol, CoH, OH (with lilac scent), be packaged in preSSure packs containing a propelling agent 0104. These terpenes solvents are widely used in perfum permitting application in the form of foams or SprayS. ery and cosmetics as fragrances. Moreover, Some of them, 0112 The fullerene clusters described hereinabove may for example, menthol, has strong bactericide properties. This be added to various type of cosmetic compositions. For reduces anS/or exclude other conservants in appropriate example, they may be added to pharmaceutical composi fullerene creams. Conservants are often allergic agents. tions which protect the human epidermis, hair and mucous 0105 The highly solubility of fullerenes in terpenes and membranes, makeup compositions for the skin and Super their derivatives allows efficient use of these solvents in ficial body growths; compositions for buccodental use Such fullerene cosmetics (e.g. allows one to achieve Sufficiently as dentifrices or ophthalmic compositions Such as collegria, high concentration of fullerenes in creams). Fullerenes are and the like. US 2005/O136079 A1 Jun. 23, 2005

0113. The fullerene clusters of the present invention are 0119) Moreover, the oil may be C-Cls fatty alcohols, present in cosmetically effective amounts or if used in Such as oleyl alcohol, cetyl alcohol and Stearyl alcohol and pharmaceutical compositions, in therapeutically effective the like. amounts, as described herein. Preferably, they are present in 0120) If present as an emulsion, the emulsified compo the compositions of the present invention from about 0.01 to Sition of the present invention includes an oil phase and an about 50% by weight of the total composition, and more aqueous phase. The oil phase preferably is present in an preferably from about 0.02 to about 10% and most prefer amount ranging from about 1% to about 75% by weight, ably from about 0.05 to about 2% by weight. based on the total weight of the composition, more prefer 0114. When the cosmetic compositions according to the ably from about 5% to about 60% by weight and most present invention are used for protecting the hair, they may preferably from about 40% to about 60% by weight. be provided in the form of Shampoos, lotions, or gels, or compositions to be rinsed, or to be applied before or after 0121 The aqueous phase may include adjuvants com Shampooing, before or after dyeing or bleaching or before, monly used in aqueous gels and cosmetic emulsions. The during, or after permanent waving of the hair or of hair aqueous phase may be present from about 0.5% to about Straightening treatments. It may also be provided in the form 20% by weight and may also include a lower C-C monoal of hair Styling or treating lotions or gels, lotions or gels for cohol and/or a polyol, Such as glycerol, butylene glycol, blow drying or hair Setting, hair lacquers, compositions for isoprene glycol, propylene glycol, ethylene glycol, and the permanent waving or hair Straightening, or compositions for like. dyeing or bleaching the hair. 0.122 Emulsifiers can be used to assist in preparing an 0115 When the composition of the present invention is emulsified cosmetic composition. Any cosmetically accept used as make-up products for the eyelashes, the eyebrows, able emulsifier can be used in an amount that provides the or the skin, it is provided in the form of foundations, desired emulsifying effect. The emulsifiers are generally lipsticks, eyeshadows, blushers, eyeliners, mascaras, or Selected from known Soaps and Surfactants. Preferably, the creams for treating the epidermis. emulsifiers are Selected from Stearic acid, Sorbitan SeS 0116. When the composition of the present invention is quinoleate, polyethylene glycol (PEG-30), dipolyhydroxys used as a pharmaceutical composition, e.g. a Sanitizing tearate, lecithin, magnesium Stearate, and derivatives and composition, a composition for reducing the appearance of mixtures thereof. The emulsifiers preferably are used in lines and wrinkles, a moisturizer or the like, it may be amounts ranging from about 0.5 to about 30% by weight, provided preferably in the form of an emulsion, Such as milk based on the total weight of the composition, more prefer or cream, gel, lotion, ointment, or vesicular dispersion, and ably from about 1% to about 12% by weight and more may contain pharmaceutically active ingredients. preferably from about 4% to about 8% by weight. 0117 The cosmetic compositions may contain natural or 0123. A thickening agent may also be present. Anythick Synthetic waxes. Natural waxes may be of animal origins, ening agent normally used in cosmetics can be used. Such as lanolin, beeswax, Spermaceti or lanolin derivatives, Examples include modified clays, Such as modified magne Such as lanolin alcohols, hydrogenated or acetylated lanolin, sium silicate (bentone gel VS38 from Rheox), hectoxite fatty acids of lanolin or acetylated lanolin alcohol, or of modified by distearyldimethylammonium chloride (bene vegetable origin, Such as carnauba, candelilla, kapok, rice, tone 38 CE from Rheox), cross-linked polyacrylic acids and hydrogenated jojoba, alfa or yapan wax or cork fiber, Sugar guar gums and celluloses which may or may not be modi cane waxes, cocoa butter or the like. Alternatively, mineral fied. waxes may be present in the cosmetic composition, Such as 0.124. The composition of the present invention can also paraffin, montan, lignite, petrolatum, petrolatum waxes or contain a film-forming compound. Film forming compounds microcrystalline waxes, ceresin, or OZokerite. Examples of can be chosen from polymers in aqueous dispersions, Such Synthetic waxes that may be used include polyethylene as, for example, acrylic, polyester and/or polyurethane poly waxes, the waxes obtained by Fischer-TropSch Synthesis and mers in aqueous dispersion, e.g. partially neutralized vinyl the linear esters resulting from the reaction of a Saturated acetate/vinyl p-tert-butyl/benzoate/crotonic acid copolymer C-Cao carboxylic acid and of a saturated Co-Cio alcohol, in aqueous dispersion. Such as myristyl myristate. Other waxes that may be used include calcium lanolates or Stearates, or hydrogenated 0.125 The compositions of the present invention may also coconut oil, and the like. contain coloring agents. These coloring agents can be either inorganic or organic pigments which are generally insoluble 0118. The cosmetic compositions may contain unmodi in aqueous and organic media or dyes which are, Soluble in fied or modified oils of vegetable or animal origin, for aqueous or organic matter. example, Sweet almond oil, avocado oil, castor oil, olive oil, jojoba oil, Sunflower oil, wheat germ oil, Sesame oil, ground 0126. A lubricity agent is another optional component. A nut oil, grapeseed oil, Soybean oil, Safflower oil, coconut oil, lubricity agent generally aids in creating a Soft and Smooth maize oil, hazelnut oil, karite butter, palm oil, apricot kernel feel of the composition to the hands. Examples include oil, calophyllum oil or perhydroSqualine. Moreover, the oil benzoic acid esters of C-C alcohols, Volatile Silicones phase may be a mineral oil, for example, liquid paraffin, Such as cyclomethicones, dimethicones and derivatives liquid petrolatum and the like. The oil may be a Synthetic oil, thereof. Examples of Silane containing compounds useful in e.g. fatty acid esters, Such as isopropyl myristate, isopropyl the present invention include cyclomethicone tetramer and palmitate, 2-ethylhexyl palmitate, penicillin oil (Stearyl pentamer (available as Dow Corning 244 or 245 Fluids) or octonate), unsaturated fatty acids, Such as oleic, palmetic, non-volatile Silicones Such as Stearyl dimethicone (available Stearic, behenic, linoleic, lanoleic acid or volatile or non as Dow Corning 2503 Cosmetic wax), or derivatives thereof, Volatile isoparaffins, e.g. C-C isoparaffins, and the like. Such as cyclomethiconepolyol, dimethiconepolyol, cetyl US 2005/O136079 A1 Jun. 23, 2005 dimethicone copolyol, phenyl methicone, phenyl trimethi that are useful in absorbing, Screening or preventing ultra cone, and the like. Those skilled in the art will also appre Violet rays from penetrating the Skin. Preferably, the Sun ciate that the Silicone containing compounds may also Screen agent is titanium dioxide or Zinc oxide and more function as an emulsifier. preferably the Sunscreen agent is coated with a polymeric 0127. The silicone containing compounds are preferably material or other cosmetically acceptable coating. Examples present in an amount ranging from about 1% to about 50% of Sunscreen agents are micronized titanium dioxide coated by weight, based on the total weight of the composition, with aluminum Stearate, or Co-Cs polyfluoroalkyl phos more preferably from about 5% to about 30% by weight and phate, polymer coated Zinc oxide, aminobenzoic acid most preferably from about 10% to about 25% by weight. (PABA) and its esters, benzophenone-3, octyl Salicylate, 0128. A moisturizing agent may also be added to the menthyl anthranilate, phenylbenzimidazole Sulfonic acid cosmetic composition. A "moisturizing agent' is an agent and the like. that provides a moisturizing effect to the skin, e.g. humec 0134) Specifically, the Sunscreen agent provides a pro tants. The moisturizing agent is present in a moisturizing effective amount. Examples of moisturizing agents include tection factor (SPF) in the range of 2-12 for minimal, 12-30 glycerin, butylene glycol, propylene glycol, Sorbitol, Sodium for moderate and above 30 for high Sun protection. PCA, glucam E-10, glucam E-20, and the like. Preferably 0.135 The balance of the composition is comprised of the moisturizing agent is present in an amount ranging from customary additives Selected from auxiliaries, fillers, about 0.1% to 10% by weight of the total composition, and organic Solvents (Such as alcohols and oils), buffers, per more preferably from about 0.1 to about 5% by weight and fumes, Self-tanning agents (e.g. dihydroxy acetone) and the most preferably from about 1% to about 5% by weight. like and other cosmetically acceptable carriers and fillers. 0129. Additionally, emollients may optionally be present. Other conventional additives, that can be used in the present It is preferred that the composition contains one or more cosmetic compositions, include dispersants and preserva emollients. Emollients are used to impart a Smooth and Soft tives. The amount of conventional additives typically range feeling to the Skin Surface. This is effected without measur from about 0 to about 20% by weight based on the total ably affecting the skin hydration level and/or the Skin liquid weight of the composition, preferably from about 1% to barrier. Examples of emollients include vegetable triglycer about 15% by weight and more preferably from about 4% to ides, Such as avocado oil, olive oil, Sunflower oil, organic about 10% by weight. acid esters such as Sorbitan oleate, myristyl myristate, iso 0.136. It will be appreciated that the remaining percentage propyl myristate, glycol oleate, mineral oil, glycerin, petro or balance of the composition is water. Water acts as a latum, petroleum jelly, and the like. Emollients may be vehicle to ensure even distribution of the composition to the present in an amount ranging from about 1% to about 50% skin. It is preferred that the water utilized is deionized or of the composition, more preferably for about 5% to about distilled water and the amount of water is typically any 40% and most preferably from about 10% to about 25% of where from about 10% to about 80% by weight, and most the composition. preferably from about 20% to about 40% by weight. 0130. Additionally, antioxidants may also be present in the cosmetic composition of the present invention. The 0.137 In a preferred embodiment, the cosmetic compo antioxidant may be natural or Synthetic. Examples include Sition of the present invention is a cream or lotion or tocopherol, Vitamin E derivatives, e.g. Vitamin Elinoleate, ointment, but most preferably a cream. The carrier is pref Vitamin E, Vitamin E POE Succinate, Vitamin E acetate, erably water. The preferred cream composition is formulated ascorbic acid, ascorbyl palmitate and ascorbyl-PMG. It is as an oil in water emulsion that contains the necessary used in effective amounts to neutralize harmful oxidants, e.g. common cosmetic ingredients known to one skilled in the art Singlet oxygen. Preferably, it is present within the range of for ensuring high user properties, in addition to the fullerene cluster component. In one preferred embodiment, these about 0.1% to about 5% by weight and more preferably from ingredients include petrolatum, especially white petrolatum, about 0.5% to 1% by weight. preferably in an amount ranging from about 0.5% to about 0131 The cosmetic composition may also contain ingre 1% by weight of the composition, lanolin alcohol preferably dients that reduce the oily feel of emollients in the compo in an amount ranging from about 0.5% to about 1% by Sition, e.g., cream, known in the art, e.g., PPG-2-myristyl weight of the composition, PPG-2-myristyl ether propi ether propinate, isopropyl palmitate and the like. If present, onate, preferably in an amount ranging from about 3% to they are present in an amount from about 1% to about 30% about 6% by weight of the composition, mineral oil, pref and more preferably from about 5% to about 25% and most erably in an amount ranging from about 5% to about 10% by preferably about 10% to about 20% by weight of the weight of the composition, triethanolamine, preferably in an composition. amount ranging from about 0.2% to about 0.8% by weight 0132 A pH adjusting agent is commonly used to adjust of the composition, glycerol, preferably distilled, and pref the acidity of the composition to a desirable range, prefer erably in an amount ranging from about 2% to about 4% by ably to a pH of about 6 to 8. An example is aminomethyl weight of the composition, Stearic acid, preferably in an amount ranging from about 15% to about 20% of the propanol. This pH adjusting agent is added in an amount composition, isopropyl palmitate preferably in the amount effective to change the pH of the composition to the desired of about 10% to about 15% by weight of the composition pH range. Preferably, it is present in an amount that is leSS and the remaining amount is water. Fragrances, perfumes, than 0.4% by weight of the total composition. Vitamins and other common ingredients known to one of 0.133 A Sunscreen agent may also optionally be present. ordinary skill in the art normally present in cosmetic or The expression “Sunscreen agent” denotes Sunscreen agents pharmaceutical compositions Such as those outlined herein US 2005/O136079 A1 Jun. 23, 2005

above as well as antioxidants and coloring agents, depend the formation of ODC in the epidermis; see R. L. Binder et ing on the Specific cream formulation desired, may also be al., Carcinogensia, Vol. 10, No. 12, 2351-2357 (1989). Some present. fullerene compounds are capable of reducing the level of ODC in the skin. Fullerene clusters possess the same prop 0.138. The cosmetic compositions of the present inven erty due to their ability to deliver active fullerene molecules tion containing fullerene clusters, prepared as described into the Skin cells. Thus the cosmetic compositions of the hereinabove have Several utilities. First, they produce a invention can make it possible, in addition, to prevent or marked rejuvenating effect on the Skin, described in Some limit the risks of skin cancers. This has been confirmed by preferred embodiments of this invention. the positive changes in the Skin Superficial body growth, 0139 Inasmuch as double bonds in the fullerenes are observed in experiments on topical application of a compo readily available for reduction-oxidation (redox) reactions, Sition of the present invention to the skin Superficial body. the cosmetic compositions of the present invention have 0143. The fullerene containing cosmetics of the present Strong anti-oxidant properties that are likely, depending on invention destroy bacterial toxins on the Outer Surface layer the fullerene clusters capacity, to induce Strong negative of the Skin, which can be judged from Steady exclusion of catalysis that blockS chain radical oxidation processes. It is the characteristic odor pertaining to toxins, upon application believed that free radicals produced during metabolic reac of most of compositions Studied So far. Furthermore, the tions in the skin cells are one of the major factors of skin fullerene containing cosmetics of the present invention are aging. The cosmetic compositions of the present invention, bactericides and protect the skin from bacterial attack. The when applied to the skin in effective amounts, prevent fullerenes clusters and fullerene herein are artificial mol free-radical damage to cells, thus rejuvenating the Skin, and ecules to which the bacteria have no natural defenses. in particular reducing the appearance of wrinkles. Bacteria are free living organisms equipped with enzymes to 0140. The compositions of the invention can be applied break down and assimilate a wide variety of molecules. to the skin on a daily basis and more preferably twice daily. However, without wishing to be bound, it is believed that In order to achieve pronounced and Stable rejuvenating bacteria cannot assimilate the fullerene molecule, while the effects, they should be applied regularly for weeks or latter is deemed capable of blocking enzyme activity by months, although the effectiveness of the compositions restricting conformational movements in enzyme macro usually gives visible results starting from the first few molecule, thus eventually causing the bacteria demise. applications. The rate and duration of application can be 0144. The fullerene cluster of the present invention varied, however, depending on the concentration of effective exhibits anti-inflammatory and antiseptic activity. They have ingredients. Skilled artisans are capable of designing a reparative activity for wounds, as defined herein, and Suitable application regimen to provide the requisite reju decrease water accumulation under the Skin and water Venating effect. Swelling of tissue. They have an anti-genesis effect and 0141 Mitochondria in the human body produce kilo retard granulated tissue when the tissue is repaired and grams of free radicals annually in the process of normal retard the growth of epithelial layer of Skin exceSS. cellular metabolism. The capacity of cells to defend against oxidation damage initiated by free radicals reduces with 0145 More specifically, the fullerene composition com time, which is the cause of cellular and organism malfunc prising fullerene clusterS is a beneficial agent for the tions generally recognized as normal aging phenomena. enhancement or improvement of the healing of wounds in Accelerated aging occurs when additional Sources of free Soft tissues (i.e. non-mineralized tissues) Such as collagen or radicals appear. Some atmospheric pollutants, Such as Sulfur epithelium containing tissues, including skin and mucosa, dioxide, OZone and nitrogen oxides, possess free radical muscle, blood and lymph vessels, nerve tissues, glands, initiating activity, and thus represent additional exogenous tendons, eyes and cartilage. It exerts especially useful effects Sources of free radicals. Living cells that are in permanent in the healing or prophylaxis of Soft tissue wounds. contact with the external medium (especially the skin, the 0146 Accordingly, the present invention relates to the Scalp and certain mucous membranes) are particularly Sub use of fullerene clusters in a pharmaceutical and/or cosmetic jected to toxic effects of gaseous pollutants. These effects composition i) for healing of a wound, ii) for improving result in accelerated aging of the skin, manifested by a healing of a wound, and/or iii) for Soft tissue regeneration complexion lacking brightness and the premature formation and/or repair. of wrinkles, and also in a decrease in the Vitality and a dull 0147 In another aspect, the invention relates to a method appearance of the hair. The cosmetic compositions of the of improving the healing of a wound or of promoting Soft invention are effective in reducing accelerated aging of the tissue regeneration and/or repair, the method comprising skin, and in revitalizing hair. administering, to a mammal in need thereof, a therapeuti 0142. Another exogenous source of free radicals is cally or prophylactically effective amount of fullerene clus brought to the skin, hair and mucous membranes by expo terS. Sure to ultraViolet rays. Besides being capable of causing aging phenomena, UV rays are currently considered a major 0.148. Further, the fullerene clusters have anti-bacterial factor in inducing skin tumors. Radical Species formed by and/or anti-inflammatory properties that can be used for UV radiation are particularly considered culprits in the treatment of both Soft and hard (i.e. mineralized) tissue oxidation of skin lipids, and it is thought that lipid peroxides conditions. are one of the factors which trigger photocarcinogenesis. It 0149. As used herein, wounds and/or ulcers are normally is known in particular that the induction of ornithine decar found protruding from the Skin or on a mucosal Surface or boxylase (abbreviated ODC) is an early marker for skin as a result of an infarction in an organ (“stroke”). A wound tumors, and that organic peroxides are capable of inducing may be a result of a Soft tissue defect or a lesion or of an US 2005/O136079 A1 Jun. 23, 2005

underlying condition. In the present context the term "skin' ischemic ulcers, preSSure Sores, fistulae, lacerations, Severe relates to the outermost Surface of the body of an animal bites, thermal burns and donor site wounds (in soft and hard including a human and embraces intact or almost intact skin tissues) and infarctions. as well as an injured Skin Surface. The term "mucosa' relates 0154) In other aspects of the invention, the wound to be to undamaged or damaged mucosa of an animal Such as a prevented and/or treated is Selected from the group consist human and may be the oral, buccal, aural, nasal, lung, eye, ing of aseptic wounds, infarctions, contused wounds, incised gastrointestinal, vaginal, or rectal mucosa. wounds, lacerated wounds, non-penetrating wounds, open 0150. In the present context the term “wound” denotes a wounds, penetrating wounds, perforating wounds, puncture bodily injury with disruption of the normal integrity of tissue wounds, Septic wounds and Subcutaneous wounds. Structures. The term is also intended to encompass the terms 0.155) Other wounds which are of importance which can “sore”, “lesion”, “necrosis” and “ulcer'. Normally, the term be treated or prevented by the fullerene cluster in connection "Sore' is a popular term for almost any lesion of the skin or with the present invention are wounds like ischemic ulcers, mucous membranes and the term “ulcer is a local defect, or preSSure Sores, fistulae, Severe bites, thermal burns and excavation, of the Surface of an organ or tissue, which is donor Site wounds. produced by the Sloughing of necrotic tissue. Lesion gen 0156 Ischemic ulcers and pressure Sores are wounds erally relates to any tissue defect. Necrosis is related to dead which normally only heal very slowly and especially in Such tissue resulting from infection, injury, inflammation or inf cases an improved and more rapid healing is of course of arctions. great importance for the patient. Furthermore, the costs 0151. The term “wound' used in the present context involved in the treatment of patients Suffering from Such denotes any wound and at any particular stage in the healing wounds are markedly reduced when the healing is improved proceSS including the Stage before any healing has initiated and takes place more rapidly. or even before a specific wound like a Surgical incision is O157 Donor site wounds are wounds which e.g. occur in made (prophylactic treatment). connection with removal of hard tissue from one part of the body to another part of the body e.g. in connection with 0152 Examples of wounds which can be prevented and/ transplantation. The wounds resulting from Such operations or treated in accordance with the present invention are, e.g., are very painful and an improved healing is therefore most aseptic wounds, contused wounds, incised wounds, lacer valuable. The fullerene clusters or compositions containing ated wounds, non-penetrating wounds (i.e. wounds in which Same of the present invention are useful in treating Such there is no disruption of the skin but there is injury to wounds. underlying structures), open wounds, penetrating wounds, perforating wounds, puncture wounds, Septic wounds, Sub 0158. The term “skin' is used in a very broad sense cutaneous wounds, and the like. Examples of Sores which embracing the epidermal layer of the Skin and-in those can be prevented and/or treated in accordance with the cases where the skin Surface is more or less injured-also present invention include bed Sores, canker Sores, chrome the dermal layer of the skin. Apart from the Stratum cor Sores, cold Sores, pressure Sores, and the like. Examples of neum, the epidermal layer of the skin is the Outer (epithelial) ulcers which can be prevented and/or treated in accordance layer and the deeper connective tissue layer of the skin is with the present invention include, e.g., peptic ulcer, duode called the dermis. nal ulcer, gastric ulcer, gouty ulcer, diabetic ulcer, hyper 0159. Since the skin is the most exposed part of the body, tensive ischemic ulcer, stasis ulcer, ulcus cruris (venous it is particularly Susceptible to various kinds of injuries Such ulcer), Sublingual ulcer, Submucous ulcer, Symptomatic as, e.g., ruptures, cuts, abrasions, burns and frostbites or ulcer, trophic ulcer, tropical ulcer, Veneral ulcer, e.g. caused injuries arising from various diseases. Furthermore, much by gonorrhoea (including urethritis, endocervicitis and proc skin is often destroyed in accidents. However, due to the titis). Conditions related to wounds or Sores which may be important barrier and physiologic function of the skin, the Successfully treated according to the invention are burns, integrity of the skin is important to the well-being of the anthrax, tetanus, gas gangrene, Scalatina, erysipelas, Sycosis individual, and any breach or rupture represents a threat that barbae, folliculitis, impetigo contagiosa, or impetigo must be met by the body in order to protect its continued bullosa, and the like. There is often a certain overlap existence. between the use of the terms “wound” and “ulcer' and “wound” and "sore” and, furthermore, the terms are often 0160 Apart from injuries on the skin, injuries may also used at random. Therefore as mentioned above, in the be present in all kinds of tissues (i.e. Soft and hard tissues). present context the term "wounds' encompasses the term Injuries on Soft tissues including mucosal membranes and/or “ulcer”, “lesion”, “Sore” and “infarction', and the terms are skin are especially relevant in connection with the present indiscriminately used unless otherwise indicated. invention. The present fullerene clusters or compositions 0153. The kinds of wounds to be treated according to the containing Same are useful in treating the various wounds, invention include also i) general wounds Such as, e.g., Sores, and ulcers described herein. Surgical, traumatic, infectious, ischemic, thermal, chemical 0.161 Healing of a wound on the skin or on a mucosal and bullous wounds; and ii) wounds on the skin Such as, e.g., membrane undergoes a Series of Stages that results either in neoplasm, burns (e.g. chemical, thermal), lesions (bacterial, repair or regeneration of the skin or mucosal membrane. In Viral, autoimmunological), bites and Surgical incisions. recent years, regeneration and repair have been distin Another way of classifying wounds is as i) Small tissue loss guished as the two types of healing that may occur. Regen due to Surgical incisions, minor abrasions and minor bites, or eration may be defined as a biological proceSS whereby the as ii) significant tissue loss. The latter group includes architecture and function of lost tissue are completely US 2005/O136079 A1 Jun. 23, 2005 renewed. Repair, on the other hand, is a biological proceSS in Subsequent events of the healing process. The macroph whereby continuity of disrupted tissue is restored by new ages attract fibroblasts which start the production of col tissueS which do not replicate the Structure and function of lagen. the lost ones. 0169 ii) Granulation Tissue Formation and Re-Epi 0162 The majority of wounds heal through repair, mean thelization ing that the new tissue formed is Structurally and chemically unlike the original tissue (Scar tissue). In the early stage of 0170 Within 48 hours after wounding, fibroblasts begin the tissue repair, one proceSS which is almost always to proliferate and migrate into the wound Space from the involved is the formation of a transient connective tissue in connective tissue at the wound edge. The fibroblasts produce the area of tissue injury. This proceSS Starts by formation of collagens and glycosaminoglycans and, inter alia, low oxy a new extracellular collagen matrix by fibroblasts. This new gen tension at the wound StimulateS proliferation of endot extracellular collagen matrix is then the Support for a helial cells. The endothelial cells give rise to the formation connective tissue during the final healing process. The final of a new capillary network. healing is, in most tissues, a Scar formation containing 0171 Collagenases and plasminogen activators are connective tissue. In tissueS which have regenerative prop secreted from keratinocytes. If the wound is left undisturbed erties, Such as, e.g., Skin and bone, the final healing includes and well-nourished with oxygen and nutrients, keratinocytes regeneration of the original tissue. This regenerated tissue will migrate over the wound. Keratinocytes are believed has frequently also Some Scar characteristics, e.g. a thick only to migrate over viable tissue and, accordingly, the ening of a healed bone fracture. keratinocytes migrate into the area below the dead tissue and 01.63 Under normal circumstances, the body provides the crust of the wound. mechanisms for healing injured Skin or mucosa in order to 0172 The wound area is further decreased by contrac restore the integrity of the Skin barrier or the mucosa. The tion. repair proceSS for even minor ruptures or wounds may take a period of time extending from hours and days to weekS. 0173 iii) Dermal Remodelling However, in ulceration, the healing can be very slow and the 0.174 As soon as the re-epithelization is completed the wound may persist for an extended period of time, i.e. remodelling of the tissue begins. This phase, which lasts for months or even years. Several years, restores the Strength to the wounded tissue. 0164. The stages of wound healing normally include inflammation (normally 1-3 days), migration (normally 1-6 0.175 All of the above-mentioned healing-processes take days), proliferation (normally 3-24 days) and maturation considerable time. The rate of healing is influenced by the (normally 1-12 months). The healing process is a complex wounds freedom from infection, the general health of the and well orchestrated physiological process that involves individual, presence of foreign bodies, etc. Some pathologic migration, proliferation and differentiation of a variety of conditions like infection, maceration, dehydration, generally cell types as well as Synthesis of matrix components. The poor health and malnutrition can lead to formation of a healing proceSS may be separated into the following three chronic ulcer Such as, e.g., ischemic ulcers. phases: 0176 Until at least Superficial healing has occurred, the wound remains at risk of continued or new infection. There 0165) i) Haemostasis and Inflammation fore, the quicker the wound can heal, the Sooner the risk is 0166 When platelets are present outside the circulatory removed. System and exposed to thrombin and collagen, they become activated and they aggregate. Thus, platelets initiate the 0177 Thus, any procedure that can influence the rate of repair process by aggregating and forming a temporary plug wound healing or favorably influence the healing of wounds to ensure haemostasis and prevent invasion from bacteria. is of great value. The activated platelets initiate the coagulation System and 0.178 Furthermore, as almost all tissue repair processes release growth factors like platelet-derived growth factor include the early connective tissue formation, a Stimulation (PDGF) and epidermal growth factors (EGFs) and trans of this and the Subsequent processes are contemplated to forming growth factors (TGFs). improve tissue healing. 0167 The first cells to invade the wound area are neu 0179. In the present context the term “clinical healing” is trophils followed by monocytes which are activated by used to denote a situation where no tissue interruption can be macrophages. Visually observed and only discrete Signs of inflammation 0168 The major role of neutrophils appears to be clear are present Such as a light redness or a discretely Swollen ing the wound of or defending the wound against contami tissue. In addition, no complaints of pain are present when nating bacteria and to improve the healing of the wound by the organ is relaxed or untouched. removing dead cells and platelets. The infiltration of neu 0180. As mentioned above, the invention relates to the trophils ceases within about the first 48 hours provided that use of fullerene clusters, as defined herein as a wound no bacterial contamination is present in the wound. ExceSS healing agent, i.e. an agent which accelerates, Stimulates or neutrophils are phagocytosed by tissue macrophages promotes healing of dermal or mucosal wounds. Without recruited from the circulating pool of blood-borne mono wishing to be bound it is believed that the fullerene cluster cytes. Macrophages are believed to be essential for efficient promotes healing of the wound at all of the Stages indicated wound healing in that they also are responsible for phago hereinabove. Accordingly, the fullerene clusters of the cytosis of pathogenic organisms and a clearing up of tissue present invention or composition containing Same are useful debris. Furthermore, they release numerous factors involved as tissue regeneration and/or repair agent. Furthermore, due US 2005/O136079 A1 Jun. 23, 2005

to the wound healing effect, the fullerene clusters of the faecalis, S. pyogenes), StaphylococcuS (e.g. S. present invention have pain relief effect. aureus, S. epidermidis, S. Saprophyticus, S. albus), and rods, Such as Actinomyces (e.g. A. israelli), 0181. In a further aspect of the present invention, the Bacillus (e.g. B. cereus, B. Subtilis, B. anthracis), fullerene clusters of the present invention are used as CloStridium (e.g. C. botulinum, C. tetani, C. perfrin therapeutic or prophylactic agents having an anti-microbial gens, C. dificile), Corynebacterium (e.g. C. diphthe effect. They exhibit infection-decreasing properties. riae), Listeria, and Providencia. Other bacteria caus 0182. In the present context the term infection-decreasing ing infections include Propionobacterium acne and effect relates to a treating or preventive effect by the Pityosporon ovale and the like. Diseases or maladies fullerene clusters on an infection in a tissue of an individual caused by or resulting from infections by these when the tissue or the individual is treated with the fullerene bacteria are also treated by the fullerene clusters or clusters. compositions containing Same of the present inven 0183 The term “infection” relates to the invasion and tion. multiplication of microorganisms in body tissueS or accu 0188 The fullerene clusters or compositions containing mulation on the tissues, which may be clinically unapparent Same are also used for the treatment of an infection caused or result in local cellular injury due to competitive metabo by a Spirochete Such as, e.g., Borrelia, Leptospira, Tre lism, enzymes, toxins, intracellular replication or antigen pOnema or Pseudomonas. antibody response. 0189 The fullerene clusters can be used in conjunctions 0184. In accordance with the present invention, the infec with an antimicrobial. An antimicrobial to be used in com tion to be prevented and/or treated may be caused by a bination with the fullerene clusters include an antimicrobial microorganism. The microorganisms of interest according to that has an antimicrobial action through inhibition of cell the present invention include bacteria, Viruses, yeast, molds, wall Synthesis, Such as beta-lactams and Vancomycin, pref protozoa and rickettsiae. erably penicillins, Such as amdinocillin, amplicillin, amox 0185. In the present context the term “anti-bacterial icillin, azlocillin, bacampicillin, benzathine pinicillin G, effect” means that the growth of bacteria is Suppressed or the carbenicillin, cloxacillin, cyclacillin, dicloxacillin, methicil bacteria are destroyed. The term is not limited to certain lin, meZlocillin, nafcillin, oxacillin, penicillin G, penicillin bacteria but encompasses in general any bacteria. However, V, piperacillin, and ticarcillin; cephalosporins, Such as the the invention is focused on i) pathogenic bacteria which first generation drugs cefadroxil, cefazolin, cephalexin, cause diseases in mammals including humans and/or ii) cephalothin, cephapirin; and cephradine, the Second genera bacteria which normally are present in a mammal body and tion drugs cefaclor, cefamandole, cefonicid, ceforamide, which under certain conditions may cause unwanted condi cefoxitin, and cefuroxime, and the third generation cepha tions in the body. losporins, cefoperaZone, cefotaxime, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam, carbapenems 0186 Accordingly, the invention relates to the use of Such as imipenem; and monobactams Such as aztreonam, fullerene clusters for the prevention of or treatment of and the like. bacterial growth on a body Surface Such as the Skin, a mucosal Surface or a nail or a tooth Surface. 0190. Other antimicrobial drugs which can be used in conjunction with the fullerene clusters of the present inven 0187. The fullerene clusters may be used for the tion include those antimicrobials with action through inhi treatment of an infection caused by bacteria together bition of protein Synthesis, Such as chloramphenicol; other with or without the presence of an antimicrobial. tetracyclines, preferably demeclocycline, doxycycline, Gram negative bacteria to be treated with the methacycline, minocycline, and Oxytetracycline, aminogly fullerene clusters include cocci, Such as Neisseria cosides Such as amikacin, gentamicin, kanamycin, neomy (e.g. N. meningitis, N. gonorrhoeae), and Acineto cin, netilmicin, paromomycin, Spectinomycin, Streptomycin, bacter or rods, Such as Bacteroides (e.g. B. fragilis), and tobramycin; polymyxins Such as colistin, colistimathate, Bordetella (e.g. B. pertussis, B. parapertussis), Bru and polymyxin B, and erythromycins and lincomycins, cella (e.g. B. melitentis, B. abortuS Bang, B. Suis), antimicrobials with action through inhibition of nucleic acid Campylobacter (e.g. C. jejuni, C. coli, C. fetus), Synthesis in particular Sulfonamides Such as Sulfacytine, Citobactor, Enterobacter, Escherichia (e.g. E. coli), Sulfadiazine, Sulfisoxazole, Sulfamethoxazole, Sulfame Haemophilus (e.g. H. influenzae, H. para-influen thizole, and Sulfapyridine, trimethoprim, quinolones, novo zae), Klebsiella (e.g. K. pneumoniae), Legionella biocin, pyrimethamine, and rifampin. (e.g. L. pneumophila), Pasteurella (e.g. P. yersinia, P. multocida), Proteus (e.g. P. mirabilis, P. vulgaris), 0191 The present invention also relates to the uses of Pseudomonas (e.g. P. aeruginosa, P. pseudomallei, fullerene clusters as therapeutic or prophylactic agents hav P mailer), Salmonella (e.g. S. enteritidis, S. infantitis ing an anti-inflammatory effect. S. Dublin, S. typhi, S. paratyphi, S. Schottmulleri, S. 0.192 Several drugs are employed to suppress the mani choleraeSuis, S. typhimurium, or any of the 2,500 festations of inflammation, including the adrenocorticoster other Serotypes), Serratia (e.g. S. marscences, S. oids, the large group comprising the So called non-Steroid liquifaciens), Shigella (e.g. S. Sonnei, S. flexneri, S. anti-inflammatory drugs or NSAIDS, and drugs. Such as dysenteriae, S. boydii), Vibrio (e.g. V. cholerae, V, el immunosuppressive agents. Adrenocorticosteroids, and tor), and Yersinia (e.g. Y. enterOcolitica, Y. pseudotu especially glucocorticoids, have potent anti-inflammatory berculosis, Y. pestis). Gram positive bacteria to be effects when used in pharmacological doses. They specifi treated with the fullerene clusters include cocci, Such cally inhibit the early vascular phase of the inflammatory as StreptococcuS (e.g. S. pneumoniae, S. viridans, S. process by decreasing the vascular permeability and thereby US 2005/O136079 A1 Jun. 23, 2005 granulocyte migration. Glucocorticoids also interfere with mg of this powder is placed into a thin-walled polyethylene late inflammatory and reparative processes, in that they test tube, which is thereafter filled with deionized (DI) water inhibit the proliferation of mesenchymal cells and the pro to capacity (3 ml) and hot sealed at the open end. The sample duction of extracellular macromolecules, including pro thus prepared is inserted through the orifice in the upper lid teoglycanes and collagen. It has been shown experimentally of the electrohydraulic apparatus (FIG. 2) into the chamber that glucocorticoids inhibit, for example, macrophage func filled with DI water that is circulating through a cooler. The tion, production of humoral. antibodies, cellular immunity, Sample is Secured with a Special holder So that the fullerite and possibly the release of lySOSomal enzymes. These drugs powder is located in the upper focus of the ellipsoid. A Series may be utilized in conjunction with the fullerene clusters of of electric discharges with 2 HZ pulse frequency is effected the present invention. in the lower focus of the ellipsoid for a total of two hours with a 5 uF capacitor which is charged between the pulses 0193 The severity of tissue damage may depend on the to 6,000 V with a high voltage power supply. The apparatus antigen/antibody reaction of the organism as well as the produces about 75 Jenergy per pulse, and the pulse front rise degree of retention of inflammatory products in the affected time is about 30 ns with total pulse duration about 500 ns. area. Accumulation of mediators of local inflammation Upon completion of EH treatment the tube is unsealed and accelerates the process. In most cases the proceSS is slow, a droplet of appropriately thinned Solution of the product is with immunoinfiltration of the tissue and formation of dried and gold-coated in argon plasma to prepare the Sample granulation tissue which contains inflammatory cells. for high-resolution SEM inspection. The SEM study reveals 0194 In the present context the term “anti-inflammatory the presence of Small fullerene clusters sized down to 7 mm effect” denotes a counteracting or Suppression of inflamma in diameter, with the average diameter about 15 nm. An tion. aliquot of the fullerene cluster product is ultraSonically dispersed in a large amount of DI water to form a Solution 0.195 The inflammatory condition to be treated in accor with fullerene concentration about 0.1 mg/ml. This solution dance with the present invention may of course be any is filtered through the 0.22 um porous PTFE filter to yield inflammatory condition in?on any part of the body or any transparent yellow-brown solution of fullerene clusters that inflammatory condition present in Soft or hard tissue. is stable in the dark at 5 C for at least 5 months. The rest of 0196. In the treatment of wounds, and in the treatment the fullerene cluster product is dried in air at room tempera and/or prophylaxis of inflammation, infections and the like, ture and Stored in a refrigerator before its use in preparing the effective amount of fullerene clusters can be determined cosmetic compositions. It can be re-dispersed in water, easily by a physician. The amounts will vary depending on alcohol or oils by soft ultrasonic treatment to yield stable the health and age of the mammal being treated, the condi yellow to dark-brown transparent solutions of fullerene tion being treated, the Severity of the condition being treated, clusters, depending on type of Solvent and fullerene con and the like. A physician will be able to determine the centration, which may vary from 0.1 to 40 mg/ml in different amounts without undue experimentation. A preferred liquids used. The thus obtained fullerene clusters can be amount is the same as described herein with respect to the used in various cosmetic compositions, in accordance with cosmetic compositions. Moreover, the pharmaceutical com the present invention. positions may contain the same components as described hereinabove for the cosmetic compositions. EXAMPLE 2 0197) The cosmetic compositions and the pharmaceutical 0200. The same EH treatment as in Example 1 was compositions of the present invention may be exposed to applied to a suspension of 400 mg of 99.9 wt.% pure fullerite light. In fact, the present composition may be more effective Co in 3 ml of clear olive oil, except that total duration of the when exposed to light. This is especially true for the treatment was 4 hours. Several interruptions of the treatment pharmaceutical composition of the present invention com were necessary to adjust the clearance between electrodes, prising an effective amount of fullerene clusters especially which grows because of the electrode's Spark erosion. those used for wound healing. The pharmaceutical activity High-resolution SEM inspection revealed the presence of of the compositions of the present invention are enhanced in fullerene clusters with an average diameter of about 20 nm normal Solar or artificial light. Preferably, the light ranges in a sample prepared by 1:10,000 dilution of the as-produced from about 20 to about 100 LX light intensity. Nevertheless, product in ethanol with Subsequent drying of a droplet of the Sufficient light is obtained in normal everyday life, Such as ethanol Solution of a polished aluminum Support. The as from Sunlight as well as leSS intense light, Such as that found produced product was Stored in a refrigerator and dissolved in a room from an electric bulb or even fluorescent light, to easily under Soft ultraSonic treatment in a larger amount of effectuate the therapeutic activity, Such as wound healing, of olive or other natural oil of interest for cosmetics. the fullerene clusters in the present compositions. 0198 The following non-limiting examples of the pro EXAMPLE 3 duction of fullerene clusters and their use in a brand line of cosmetic products additionally illustrate the present inven 0201 A slurry of 100 mg of finely ground 99.9% pure fullerite Co in 200 ml of reagent grade ethanol, maintained tion. and Suspended by a magnetic Stirrer in a two-neck glass EXAMPLE 1. flask, was further circulated by a peristaltic pump at a rate of 20 ml/min in a closed contour containing a thin PTFE 0199 The solvent free fullerite Co of 99.9 wt.% purity tube passing through the upper focal point of the ellipsoidal is obtained by Subliming the crystalline Solvate of Co in chamber of FIG. 2. The conditions of the EH treatment are Vacuum, then grinding it in an agate mortar in an argon dry the same as in EXAMPLE 1 except that duration of treat box to the average crystallite size of about 10 microns. 400 ment was 4 hours. After filtering the product through a 0.22 US 2005/O136079 A1 Jun. 23, 2005 15 lum PTFE filter, a slightly opalescent reddish solution was 0216 A panel of volunteers consisting of 10 females obtained with a fullerene concentration of about 0.25 mg/ml. evaluated the above product with 0.25% content of active The SEM study established abundant fullerene clusters in fullerene compound and a control product that lacked the the size range 7 to 30 nm and larger clusters 50 to 150 nm compound, but was otherwise identical, in a single use test. in diameter which amounted to about one third of the Sample The products were applied randomly to the skin of the left mass. An aliquot of the product was Stored in a refrigerator and right hands and were worn under normal conditions for without Signs of precipitation for at least 5 months. Addi 5 hours, then evaluated for personal feelings and appearance tional prolonged ultraSonic treatment of the Sample did not of the skin. The Overall opinion of the product performance remove larger clusters. The product was concentrated and was judged in terms of skin freshness, Shine, color, Smooth dried without losing the ability to re-dissolve in ethanol, neSS, and personal feelings of pleasure and lightness of wear. water and natural oils for further use in cosmetics. In addition, color photographs of hands were taken, and images were assessed by expert graders of skin State in blind EXAMPLE 4 testing. The fullerene product was judged Superior to the 0202 Mixed fullerite containing Co and C7 in a 5:1 control product, based on panelist responses and expert molar ratio (100 mg) was dissolved in dried and distilled Visual assessment. toluene (100 ml) and added to the solution of 10 g PVP (MW 10,000-15,000) in dried and distilled chloroform (200 ml). EXAMPLE 6 Stirring of the combined solution was performed for at least 0217. The following composition was prepared: 6 hours until the mixture became brown, then the solvent was removed by vacuum drying. The Solid product was 0218. Glycerine and/or polyethylene glycol and/or mixed with water (150 ml) and subjected to 20 kHz ultra polypropylene glycol and/or polyvinylpyrrollidone sonic treatment at a power density 40 W/cm for 3 min to and/or their copolymers, and also copolymers of the yield a brown Solution, which was clearly distinct in color listed classes of polymers containing grafted biologi from the orange solution of mixed fullerite. The solution was cally active function groups: 2-30% filtered through a dense glass filter, then the Solvent was 0219 Vegetable oil and/or animal oil and/or mam removed with a rotavapor at 50 C and the product dried in mal fat, birds, fishes, amphibians, reptiles, arthro vacuum at 50 C. poda: 0.0001-5.0% 0203 The light-brown dry powder obtained was a water 0220 Mineral and/or synthetic oil (silicone, fluoro soluble form of fullerene clusters that was used subsequently silicone, siloxane, etc.) 0.0001-5.0% in preparing the cosmetic cream compositions. The Samples of these fullerene creams, incorporating Such transport 0221) Active fullerene cluster component prepared facilitating ingredients as retinal, alpha-hydroxy acids and in EXAMPLE 4: 0.05-0.25% antioxidants at a concentration amounting to about 5 wt.% 0222 Ethyl alcohol: 2.5% of the cream, have perfect homogeneous consistency, are easy to spread and are readily absorbed by different skin 0223) Extracts of simples (by weight of solid types. extracted Substance) and/or bees propolis and/or other apiculture products and/or mumie and/or birch EXAMPLE 5 tar: 0.0001-25% 0204. The following composition was prepared: 0224) Surfactant 0.0001-0.5% 0205 Animal fat: 40-80% 0225. Dye: 0.0001-0.5% 0206 Active fullerene cluster component prepared 0226 Fragrance: 0.0001-0.5% in EXAMPLE 1: 0.05-0.25% 0227 Starch, gelatin or other thickener: 0.5% 0207 Ethyl alcohol: 20-60% 0228 Water: to 100% 0208 Glycerine: 0-30% 0229. The components were mixed together and formu 0209 Polyethylene glycol (PEG) and/or polypropy lated into a cream. lene glycol (PPG) and/or polyvinylpyrrolidone (PVP) 0.0001-3% EXAMPLE 7 0210 Extracts of simples (by weight of solid 0230. A composition containing 0.05% active fullerene extracted Substance) and/or bees propolis and/or cluster component prepared as described in EXAMPLE 4 other apiculture products and/or mumie and/or birch and mixed with a Vaseline base was used to quantitatively tar: 0.0001-25% Study its reparative activity, when the cream was topically applied to wounded animal skin. The skin of three animal 0211 Surfactant: 0.0001-0.5% groups, each consisting of ten 180-200 g while rats was 0212 Dye: 0.0001-0.5% Subjected to a Specific treatment to cause formation of 2.0 by 2.0 cm conventionally aseptic wounds. The first group was 0213 Fragrance: 0.0001-0.5% then treated with the composition containing active fullerene component on the wound, and the control group with pure 0214) Water: the rest to 100% Vaseline. The third group was treated with an effective 0215. The components were mixed together and formu antiseptic, 10% methyluracyl ointment for comparison. The lated into an ointment. wound reparation experiment was carried out at illumination US 2005/O136079 A1 Jun. 23, 2005 intensity of 200 Lux. The remedy efficiency was judged by 0242. The components were mixed together and formu the rate of wound area contraction, the term of total recovery lated into an ointment. and by assessing the State of wound by hystomorphological Studies. The composition with active fullerene component EXAMPLE 9 led to the reduction of the average wound area of 45% and 0243 A panel of volunteers consisting of 6 females and 23% of the original value on the 7th and 14th day, respec 6 males was used to evaluate, in a Single use test, a tively with total coverage of the wound area with epithelium, composition Such as is described in Example 8 (containing that is, total recovery of the wound on the 14th day. In the 0.25% w/w of active fullerene compound) against a control control group, obtaining baseline the appropriate changes product that lacked the compound, but was otherwise iden were 85%, 73% and 65% of the original size on the 7th, 14th tical. The composition and control were applied to the skin and 21st day, respectively, thus showing much slower of the left and right cheeks of each volunteer either directly wound closing rate in the absence of fullerene component. or in reverse order, according to a deterministic pseudo With total recovery attained on the 28th day. The 10% random code with the same Statistical properties as a random methyluracyl ointment showed 50%, 30% and 12% of the distribution. The composition and control were worn out original wound area on the 7th, 14th and 21st day, and total doors under cold, windy weather conditions (5 C.) with recovery on the 21st day. Thus, the 0.05 fullerene cluster moderate midday Sunshine for 3 hours. After a half an hour composition reparative activity is quite comparable with that at room temperature, for the full Skin Sensitivity to return to of 10% methyluracyl ointment, and in particular, fullerene each cheek, the composition and control were evaluated for clusters are distinctly Superior in Stimulation of the rate of the Volunteers Subjective Sensations and Self evaluation of epithelization. skin appearance. The Overall opinion of the product perfor 0231 Similar studies performed at illumination intensity mance was judged in terms of skin freshness, Shine, color, of only 5 Lux (in the dark) have revealed much smaller Smoothness, and expressed comments of favorable or unfa differences between experimental and control groups. This vorable. In addition, color photographs of the left and right result evidences the photodynamic activity of the fullerene cheeks were taken, and expert graders of skin State assessed component and its important role in achieving a reparative these images. The composition was more frequently rated as effect. Without wishing to be bound, it is believed that the protective by the volunteers. The fullerene product was role of photodynamic activity in this case probably was judged Superior to the control product in respect of protect caused by the formation of Singlet oxygen, that Stimulates ing the skin against Severe weather conditions, based on intracellular reparative processes by causing a minor pri panelist responses and expert Visual assessment. mary damages to biological membranes. EXAMPLE 10 EXAMPLE 8 0244. The following composition was prepared: 0232 The following composition was prepared: 0245 Active fullerene cluster components prepared 0233. Vegetable oil and/or animal oil and/or fat of in EXAMPLE 3: O.05-0.25% mammals, birds, fishes, amphibians, reptiles, arthro 0246) Ethyl alcohol: 40-50% poda. (Examples: fat of pork, badger, bear, dog, Seal, 0247 Extracts of simples (by weight of solid crocodile, ostrich): 40-80% extracted Substance) and/or bees propolis and/or 0234 Active fullerene cluster component prepared other apiculture products and/or mumie: 0.0001 in EXAMPLE 2: O.05-0.25% 15% 0235 Stearine and/or lanoline and/or spermaceti: 0248 Fragrance of a natural vegetative origin: O.OOO1-30.0% O.OOO1-0.5% 0236 Extracts of simples (medicine plants). Examples 0249 Double-distilled water: the rest include: extracts of juniper needles and berries, Stone-pine, 0250) The components were mixed and made into a plantain, milfoil, wild rosemary, St.-John's wort, parsley, perfume. celery, roots of tormentil, leaf-buds of birch and black currant, shell of walnuts and cedar nuts, fruits of henbane, fruit body of fly-agarics (amount by weight of solid EXAMPLE 11 extracted Substance) and/or bees propolis and/or other api 0251 The following composition was prepared as a culture products and/or mumie and/or birch tar: 0.0001-20% moisturizing cream from the following: 0237) Surfactant 0.0001-0.5% 0252) Stearine cosmetic 1.5% 0238) Dye: 0.0001-0.5% 0253) Wax emulsion 2.0% 0239) Fragrance: 0.0001-0.5% 0254) Stearate PEG 400 0.5% 0240 Disperse mineral Substances, with particle 0255 Perfume oil 4.0% Size permitted for the medical purposes, Such as ZnO, TiO, MgSO, BaSO, chalk, talc, mineral 0256) Glycerol distilled 7.0% pigments: 0.0-10% 0257) Vitamin F 3.0% 0241 Water: the rest 0258 Triethanolamine 0.4% US 2005/O136079 A1 Jun. 23, 2005 17

0259 Sodium laurylsulfate ethoxylated (EMAL 270 particulate matter or impurities and has good user properties. D) 0.5% Preliminary comparative testing of this cream relative to a cream containing all of the components listed hereinabove 0260 Ethanol distilled 2.0% except the fullerene clusters on VolunteerS Suggests addi 0261) Oil extract of nettle 0.5% tional beneficial properties attributable to incorporation of an active fullerene component, including rejuvenation of the 0262) Oil extract of chamomile 0.5% skin. 0263. Oil extract of mint 0.5% EXAMPLE 13 0264. Oil extract of Sweetbrier 0.5% 0287. The following composition was prepared as a 0265 0.05% solution of fullerene clusters in Sea cream from the following components: BlackSoarn oil 5.0% 0288 TEFOSE 2561 (PEG-6 stearate cetet-20, glyc 0266 Paraoxybenzoic acid ethyl ester 0.3% erylstearate stearate 20) 5.0% 0267 Paraoxybenzoic acid propyl ester 0.2% 0289 Mineral oil 3.0% 0268 Fragrance 0.3% 0290 Cetyl stearyl alcohol 3.0% 0269 Water distilled-to 100% 0291 Dimethicone 3.0% 0270. The various components were mixed together and formulated into a moisturizing cream. 0292 Glycerine distilled 4.0% 0271 The above composition meets the cosmetic indus 0293 0.05% solution of fullerene clusters in linolic try Standards for moisturizing creams. It is a Viscous, cream acid 1.7% like, light beige to beige homogeneous mass which does not 0294 Vitamin F in oil 2.0% contain particulate matter or impurities and which has a pleasant herbal fragrance and good user properties. Prelimi 0295 Wine extract (Optivegetol wine P-150 hydro) nary comparative testing of this cream relative to a control 4.0% containing all of the above ingredients except the fullerene 0296 Ginseng extract in aqueous alcohol 5.0% clusters on VolunteerS Suggests additional beneficial prop erties from incorporation of an active fullerene component, 0297 Triethanolamine 0.2% including enhancement of anti-aging and anti-wrinkle 0298 Carbopol 980 (ETD 2001) 0.15% effects, resulting in well-expressed rejuvenation of the skin. 0299 Conservant Euksyl K 100 (benzyl alcohol, EXAMPLE 12 methylchloroisothiazolinone, methylisothiazolinone 0272. The following composition was prepared as a soft O.1% ening cream from the following components: 0300 Fragrance 0.3% 0273 Glyceryl stearate-PEG-759 stearate (CELOT 0301 Water distilled-to 100% 64) 3.5% 0302) The various components were mixed together and 0274) Mineral oil 5.0% formulated into an anti-aging cream. 0275 Cetyl stearyl alcohol 2.0% 0303. The above composition meets the cosmetic indus try Standards for anti-age creams. It is a Viscous, cream-like, 0276) Dimethicone 5.0% white light beige homogeneous mass that does not contain 0277 Glycerine distilled 5.0% particulate matter or impurities. Preliminary testing of this cream relative to a cream containing all of the above 0278. Wheat germ oil 3.0% ingredient except the fullerene clusters on VolunteerS Sug 0279 0.05% solution of fullerene clusters in Sea gests a pronounced ant-age effect due to incorporation of an BlackSoarn oil 5.0% active fullerene component. 0280 Triethanolamine 0.15% EXAMPLE 1.4 0281 Carbopol 980 (ETD 2001) 0.2% 0304. The following composition was prepared from the 0282 Conservant Euksyl K 100 (benzyl alcohol, following components as a gel: methylchloroisothiazolinone, methylisothiazolinone O.1% 0305 Carbopol 980 0.4% 0283 Fragrance 0.3% 0306 Glycerine distilled 4.0% 0284 Water distilled-to 100% 0307 Dimethicone 1.0% 0308) 0.05% solution of fullerene clusters in linolic 0285) These components were mixed together and for acid 1.7% mulated into a Softening cream. 0286 This composition meets the cosmetic industry stan 0309 Glucose (mannite) 0.5% dards for Softening creams. It represents a Viscous, cream 0310 Wine extract (Optivegetol wine P-150 hydro) like, light beige homogeneous mass which does not contain 5.0% US 2005/O136079 A1 Jun. 23, 2005 18

0311. Thiourea (carbamide) 1.0% without the PVP/fullerene component but with 0.3% ultradispersed fullerite produced as in EXAMPLE 1, which 0312 Triethanolamine 0.4% is a fullerene cluster product, produces a similarly Strong 0313 Green dye mixture (E 102, E 133) p.s. anti-inflammatory effect. 0314 Conservant Euksyl K 100 (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone EXAMPLE 16 O.1% 0337 The following composition was prepared as mois turizing vanishing cream. 0315) Fragrance 0.3% 0316 Water distilled-to 100% 0338 Fullerene C60 in cluster form 0.05% 0317. The above components were mixed together and 0339 White petrolatum USP (Source: Ultima White formulated into an anti-aging gel. Petrolatum, PENRECO) 0.8% 0318. This composition meets the cosmetic industry stan 0340 Lanolin Alcohol, NF (Super Hartolan, dards for anti-age gels. It is a gel-like, light green homoge CRODA) 1.0% neous mass that does not contain particulate matter or 0341 PPG-2-Myristyl ether propionate (Crodamol impurities and which has a pleasant fragrance. Preliminary PMP, CRODA) 4.2% comparative testing of the gel relative to a gel comprised of all of the above ingredients except the fullerene clusters on 0342 Mineral Oil (Light), NF (Drakeol 7, Light, VolunteerS Suggests a distinct anti-age effect due to incor PENRECO)8.3% poration of an active fullerene component. 0343 Triethanolamine, USP 98% (SIGMA CHEMICAL CO) 0.6% EXAMPLE 1.5 0344) Paragon III (McINTYRE) 0.6% 03.19. The following composition was prepared from the following components ad an anti-inflammatory cream: 0345 Glycerol distilled, USP (RITA) 3.3% 0320 Glyceryl stearate PEG-75-stearate (CELOT 0346) Stearic Acid, USP (Ritastearic, RITA) 16.7% 64, non-ionogenic detergent) 3.5% 0347 Isopropyl Palmitate (Estol 1517, 0321) Mineral oil 5.0% UNIQUEMA) 12.5% 0348 Fragrance: a 50:50 mixture of the fragrances 0322 Cetyl stearyl alcohol 2.0% Ocean and African Rain 0.2% 0323) Dimethicone 5.0% 0349 Water distilled, USP-to 100% 0324 Glycerine distilled 5.0% 0350 Manufacturing Procedure (100 g Batch): 0325 Oats extract 2.0% 0351 White Petrolatum, Lanolin Alcohol, and Stearic 0326 Oil extract of marigold 1.0% acid were mixed together with 4 g of Mineral Oil (Light) in 0327 Oil extract of thyme 1.0% a 250 mL beaker to form a mixture, and then the mixture was melted by heating it to 60C utilizing a hot plate/stirrer. As 0328) Oil extract of chamomile 1.0% Soon as the mixture melted, the contents of the beaker were 0329 Oil extract of liquorice 1.0% Stirred using a Teflon coated Spinbar. 0330 0.05% fullerene cluster content PVP/fullerene 0352 Separately PPG-2-myristyl ether propionate and complex 5.0% Isopropyl Palmitate were mixed together to form a Second mixture in a separate 75 mL beaker and this mixture was 0331 Triethanolamine 0.15% heated to 60 C. When the temperature of the second mixture reached 60° C., the PPG-2-myristyl ether propionate and 0332 Carbopol 980 (ETD 2001) 0.2% Isopropyl Palmitate were added to the first mixture stepwise. 0333 Conservant Euksyl K 100 (benzyl alcohol, 50 mg Of Co powder was macerated with 4.3 g of Mineral methylchloroisothiazolinone, methylisothiazolinone Oil, then subjected to ultrasonic treatment (20 kHz, 20W for O.1% 30 min) and preheated to 60 C. When the temperature of this mixture reached 60° C., it was added to the mixture con 0334 Water distilled-to 100% taining PPG-2-myristyl ether propinate, Isopropyl plamitate, 0335 The above components were mixed together and white petrolatum lanolin alcohol, and Stearic acid and min formulated into an anti-inflammatory cream. eral oil. The resulting mixture was maintained at 60 C for 20 0336. This composition meets the cosmetic industry stan min while continuing Stirring. It was noted that it was dards for anti-inflammatory creams. It is a Viscous, cream important not to overheat the mixture as Some charring of like, light beige homogeneous mass that does not contain the oils may occur which will manifest itself as a change in particulate matter or impurities and which has a pleasant the color of the Solution from a bright clear purple to a more herbal fragrance. Preliminary comparative testing of this opaque brownish colored Solution. cream relative to a cream containing the Same components 0353. In a separate container, Triethanolamine (base), as above except fullerene clusters on VolunteerS Suggests an Glycerin (emollient), Paragon III (preservative) and all of enhanced anti-inflammatory effect due to incorporation of an the water were mixed and this mixture was preheated to 60 active fullerene component. The same cream composition, C. US 2005/O136079 A1 Jun. 23, 2005

0354) The oil phase components were added to the aque 0365) Results: ous phase components and vigorously stirred (300 rpm, 0366 Bromine compounds including Br, Bra and SilverSon share mixer) until the mixture congealed and was active bromo-radicals are electrochemically generated and homogenous, then the Stirring was increased to 1000 rpm adsorbed at the Surface of the platinum electrode and then and maintained for another 20 minutes. Then the heating these radicals act as oxidating agents in redox reactions, was discontinued and the mixture was allowed to cool. reactions of electrophilic Substitution and addition to double When the mixture was at 40 C. or below, the fragrance was bonds e.g. in the fullerene molecules in the fullerene cluster added thereto and the mixture was mixed at 300 rpm for 2 of cosmetic composition. The AOA of a composition con . taining fullerene cluster was compared with a control com 0355 The resulting mixture was placed in a labeled, prised of a composition which was fullerene-free, but oth opaque container and allow to sit for 24 hours to allow erwise identical to the fullerene-containing Sample. The pearlescence to occur, which is due to in-situ Soap formation measured AOA values are presented in the following Table. and crystallization. For comparison, the AOA of frequency used in cosmetics 0356. The Co. Pearlescent cream obtained from the extracts of medicinal plants are also presented in the fol above procedures provided a high degree of emolliency and lowing table. an antioxidant potency. The emollients present in the for mulation (White Petrolatum, Mineral Oil, Glycerin, Isopro pyl Palmitate) are designed to form an occlusive barrier on Analyzed material AOA, kCb/100 g the skin and help prevent the loSS of moisture, which in turn 0.5 wt % C/PVP complex 24O.O enhances the skin's appearance by decreasing environmen PVP without Co 21.5 tal and age-related damage that can lead to Skin wrinkling, 0.5 wt.% C cluster solubilized in 21O.O discoloration, and loSS of elasticity. In addition, the Vanish Blacksoarn oil ing cream formula utilized (inclusion of PPG-2-Myristyl Blacksoarin oil without Co 12.3 0.5 wt % Co cluster solubilized in Linoleic 2O2.4 ether propionate and Isopropyl Palmitate) permits rapid Acid blending of the formulation into the Skin without the greasy Linoleic Acid without Co 4.8 feel often associated with occlusive oil-based formulations. 0.5 wt % Co cluster solubilized in 1802 Rapeseed Oil 0357 This composition meets the cosmetic industry stan Rapeseed Oil without Co 3.2 dards for moisturizing creams. It is a Viscous, cream-like, Basil herb leaves (Saturated water extract) 16.5 light purple homogeneous mass which does not contain Meadow-sweet herb leaves (Saturated 41.O water extract) particulate matter or impurities and which has a pleasant Peppermint herb leaves (Saturated water 8.5 fragrance. Preliminary testing of the cream on Volunteers extract) Suggests additional beneficial properties attributable to Peppermint Birch tree buds (Saturated 1.O.O incorporation of an active fullerene component, including water?ethanol extract) Rodiola Rosea root (Saturated 4.1 enhancement of anti-aging and anti-wrinkle effects. water?ethanol extract) Valerian herb leaves (Saturated 48 EXAMPLE 1.7 water?ethanol extract) Hawthorn Berry (Saturated water?ethanol O.36 0358 Quantitative assessment of the antioxidant activity extract of fullerene containing compositions. 0359 The quantitative assessment of the antioxidant activity of the cosmetic composition containing fullerene 0367 As shown by the data in the table, specific AOA of clusters was tested utilizing bromine-based oxidants gener Co (fullerene cluster) far Surpasses that of water and water/ ated electrochemically. ethanol eXtracts of medicinal plants and of natural oils. This clearly demonstrates the ability of fullerenes to catalytically 0360 Procedure: Scavenge and recombine free radicals in Solution. In these 0361 1. Electrogeneration of bromine-based oxi processes the fullerene molecule is not Sacrificed, contrary to dants and coulonometric tritration were performed what is happening to other known antioxidants. One with a potentiostate using 1 cm platinum working fullerene molecule can be used Several times to deactivate, electrode at a current 5 mA by rough estimation at least thousands of free radicals. 0362. 2. Bromine oxidant was generated 0.2 M KBr 0368. Unless indicated to the contrary, all percentages are dissolved in 0.1M H-SO/tartrate buffer solution, weight percentages. Moreover, the Singular shall refer to which ensure 100% yield of oxidant by current. The plural and Vice versa. final point was determined amperometrically with 0369 The above-preferred embodiments and examples two polarized platinum electrodes at E=20 mV. were given to illustrate the Scope and Spirit of the present 0363. 3. Samples for analysis in water or water/ invention. These embodiments and examples will make alcohol media were obtained by maceration of the apparent to those skilled in the art other embodiments and mixture of a cosmetic containing the active ingredi examples. These other embodiments and examples are ent listed in the following table and this media taken within the contemplation of the present invention. There in proporation 1:5 by weight. fore, the present invention should be limited only by the 0364 4. Antioxidant activity (AOA) is expressed as appended claims. amount of Coulombs spent for titration of 100 g of the analyzed Starting cosmetic Substance. What is claimed is: US 2005/O136079 A1 Jun. 23, 2005

1. A cosmetic composition which is comprised of a 20. The cosmetic composition according to claim 19 cosmetically effective amount of fullerene clusters in asso which additionally contains emollients, and anti-oxidants ciation with a cosmetically acceptable carrier. and emulsifiers. 2. The cosmetic composition according to claim 1 21. The cosmetic composition according to claim 20 wherein the fullerene clusters are present in an amount wherein the carrier is water. effective to prevent or retard free radical and molecular 22. The cosmetic composition according to claim 1 in the oxidation processes in the skin. form of a cream. 3. The cosmetic composition according to claim 1 23. The cosmetic composition according to claim 7 in the wherein the fullerene clusters are associated with a water form of a cream. Soluble polymer or porphyrin or a combination thereof. 24. The cosmetic composition according to claim 21 4. The cosmetic composition according to claim 3 wherein glycerol is additionally present. wherein the water Soluble polymer is polyvinyl pyrrolidone, 25. The cosmetic composition according to claim 24 polyethylene glycol, polypropylene glycol, copolymers of which additionally contains petrolatum, mineral oil, glyc Vinyl pyrrolidine, ethylene glycol or propylene glycol. erin, isopropyl palmitate, PPG-2-myristyl ether propionate 5. The cosmetic composition according to claim 1 isopropyl palmitate and lanolin alcohol. wherein the fullerene clusters are present in an amount 26. The cosmetic composition according to claim 7 addi ranging from 0.01 to about 50% by weight relative to the tionally comprising white petrolatum in an amount ranging total weight of the composition. from about 0.5% to about 1.5% by weight, Lanolin Alcohol, 6. The cosmetic composition according to claim 5 ranging from about 0.5% to about 1.5% by weight, PPE-2- wherein the fullerene cluster is present in an amount ranging myristyl ether propionate ranging from about 3% to about from about 0.02% to about 10% by weight of the compo 6% by weight mineral oil ranging from about 5% to about Sition. 10% by weight, triethanolamine ranging from about 0.2% to 7. The cosmetic composition according to claim 6 about 0.8%, glycerol ranging from about 2% to about 4% by wherein the fullerene cluster is present in an amount ranging weight, stearic acid ranging from about 15% to about 20% from about 0.25% to about 2% by weight of the composi by weight, isopropyl palmitate ranging from about 10% to tion. about 15% by weight of the total cosmetic composition and 8. The cosmetic composition according to claim 1 which the remainder is water. additionally comprises a mineral oil, animal oil, or vegetable 27. The cosmetic composition according to claim 26 oil or synthetic oil. additionally containing a fragrance and an anti-oxidant. 9. The cosmetic composition according to claim 1 which 28. A method of reducing damage by free radicals to the additionally comprises at least one of the following: a healthy skin or mucous membranes of a mammal compris film-forming compound, an emulsifier, a thickening agent, a ing applying to the healthy Skin or mucous membrane of Said lubricant, a coloring agent, a moisturizing agent, an anti mammal the cosmetic composition according to claim 1 in oxidant, an emollient, a pH adjusting agent, a preservative, an amount effective to protect the skin form free radicals. a Sunscreen agent, a buffer, perfume, an additive preventing 29. A method of deactivating skin toxins present on the perspiration or an additive repelling Sanguivorous insects or skin of a mammal which comprises applying to the skin of bactericides. Said mammal the cosmetic composition according to claim 10. The cosmetic composition according to claim 1 com 1 in an amount effective to deactivate the skin toxins. prised of one type of fullerene. 30. A method for the treatment of wounds in a mammal which comprises administering onto the wound a wound 11. The cosmetic composition of claim 10 wherein the healing effective amount of the cosmetic composition of fullerene is Co. claim 1. 12. The cosmetic composition according to claim 10 31. The method according to claim 30 wherein the wound wherein the fullerene is Co. is Selected from the group consisting of aseptic wounds, 13. The cosmetic composition according to claim 1 contused wounds, incised wounds, lacerated wounds, non wherein the fullerene is a mixture of Co and Co. penetrating wounds, open wounds, penetrating wounds, 14. The cosmetic composition according to claim 1 perforating wounds, puncture wounds, Septic wounds, inf wherein the fullerene clusters are formed by fragmenting arctions and Subcutaneous wounds. fullerites to nanometer Size in a liquid media. 32. The method according to claim 30 wherein the wound 15. The cosmetic composition according to claim 14 is Selected from the group consisting of ischemia, ulcers, wherein fragmentation is effected through shock wave, preSSure Sores, fistulae, and thermal burns. electrohydraulic impact, ultraSonic wave treatment or acous 33. A method for the treatment or prophylaxis of infection tic wave treatment. on the skin of a mammal comprising administering to the 16. The cosmetic composition according to claim 14 Surface of the skin of a mammal, a pharmaceutically effec wherein fragmentation is effected by electrohydraulic tive amount of the composition according to claim 1. impact. 34. The method according to claim 33 wherein the infec 17. The cosmetic composition according to claim 14 tion is caused by a microorganism. wherein the liquid media is water, alcohol, Synthetic oil, 35. The method according to claim 34 wherein the infec natural oil or mineral oil. tion is caused by bacteria. 18. The cosmetic composition according to claim 1 36. A method for the treatment of an inflammatory con wherein the carrier is water, ethanol or mixture thereof. dition in a mammal which comprises administering topically 19. The cosmetic composition according to claim 7 to the skin of the mammal a pharmaceutically effective wherein the carrier is water, ethanol or mixture thereof. amount of the composition according to claim 1. US 2005/O136079 A1 Jun. 23, 2005 21

37. The cosmetic composition according to claim 1 39. The cosmetic composition according to claim 38 wherein the fullerne clusters are associated with a terpene or wherein the terpene or derivative thereof is geraniol, cit derivative thereof, Said derivative consisting of an alcohol, rinellol, citrel, linallyl acetate, menthol or terpeneol. aldehyde, ketone, lower alkyl ether or lower alkyl ester of the terpene. 38. The cosmetic composition according to claim 37 wherein the terpene contains 10 m carbon atoms, where m is 1 to 10.