WO2020024703A1 - 一种水溶性富勒烯外用组合物 - Google Patents

一种水溶性富勒烯外用组合物 Download PDF

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WO2020024703A1
WO2020024703A1 PCT/CN2019/090926 CN2019090926W WO2020024703A1 WO 2020024703 A1 WO2020024703 A1 WO 2020024703A1 CN 2019090926 W CN2019090926 W CN 2019090926W WO 2020024703 A1 WO2020024703 A1 WO 2020024703A1
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fullerene
composition
optionally
group
dispersion system
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PCT/CN2019/090926
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English (en)
French (fr)
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李慧
王春儒
许哲
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北京福纳康生物技术有限公司
中国科学院化学研究所
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Priority to EP19844366.5A priority Critical patent/EP3848014A4/en
Publication of WO2020024703A1 publication Critical patent/WO2020024703A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/044—Suspensions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use

Definitions

  • the invention relates to the field of daily chemicals, in particular to a composition for external use having a cosmetic effect.
  • Fullerene is a carbon allotrope with diamond and graphite.
  • C60 is a spherical molecule composed of 60 carbon atoms. It consists of 12 pentagons and 20 hexagons. Each carbon atom and three adjacent carbon atoms are hybridized to form a bond through SP 2 and are shaped like footballs. Called CITE.
  • a series of molecules with a cage-like carbon atom cluster structure are collectively referred to as molecules. They are collectively referred to as caged Note> ⁇ Cite> ⁇ Auene derivatives and heterocyclic fullerenes.
  • Fullerene's large ⁇ -bond conjugate system composed of multiple P orbitals makes it have a strong ability to accept electrons. Because of its unique structure and physical and chemical properties, it has excellent free radical scavenging properties. It is called “Free radical sponge” also shows excellent antioxidant properties. It has attracted wide attention in the fields of cosmetic materials and biomedicine.
  • C60 By embedding C60 in a surfactant, C60 can still eliminate active oxygen in cells, inhibit mitochondrial depolarization, activation of cysteine proteases, exposure of phosphatidylserine on cell membranes, and DNA division. Protects cells from the effects of oxidative apoptosis.
  • the C60 liposome complex plays an antioxidant role by defending against UVA damage to skin structure, cell nucleus and collagen fibers, and penetration into human skin tissues. It is 172 times more vitamin C and is able to affinity free radicals.
  • fullerene-related products such as C60-PVP, application numbers: 200480005008.1, 200580049615.2. Due to the limitation of the preparation process and the composite characteristics of PVP and C60, the content of C60 in this compound is not More than 1%, coupled with the obvious film-forming properties of PVP, excessive application on the skin surface will play a certain hindrance to the performance of certain cosmetics.
  • C60-squalane, application number 201510427642.4 but the solubility of C60 in squalane is limited, and squalane is an oil solution, which limits the use of this series of products.
  • Fullerene nanosuspension CN201510971343.7 but this component is a fullerene component of large particles. After it is added to the formula, it will affect the stability, appearance and comfort of the formula, and the fullerene component of large particles is difficult to The skin plays a repairing role, and can only adhere to the surface of the skin, acting as a barrier.
  • Fullerene is a non-polar molecule with strong hydrophobicity and can only be dissolved in non-polar organic solvents such as toluene, benzene, cyclohexane, and chloroform which are harmful to living organisms.
  • the hydrophobic nature of fullerene itself directly affects the exertion of its biological activity.
  • fullerene is made into a solution type that is easy for the skin to quickly absorb its molecular state, and fullerene is compounded with skin-friendly type
  • the composition has not been studied.
  • the water-soluble fullerene raw materials obtained by the invention are all cluster-like, and are uniform and transparent in an aqueous solution, stable and not sedimented.
  • the selected excipients do not have the properties of a surfactant, will not have an irritating effect on the skin, and have a good repair and moisturizing effect on the skin.
  • the fullerene content in the composition is high, and the effect is better.
  • the fullerene-containing composition invented by the invention patent ensures that the fullerene is well dispersed in the selected solvent, and the obtained fullerene-containing composition has stable properties and can be used in any external formulation.
  • the fullerene in the composition of the present invention is in a dissolved state, and as a component of an external product, it can better act on the skin.
  • the object of the present invention is to provide a fullerene composition, in which the fullerene is in a dissolved state and is quickly absorbed, and has a cosmetic effect such as moisturizing, water-holding, and anti-oxidation.
  • the present invention provides a fullerene composition
  • a fullerene composition comprising a carbohydrate adjuvant and a fullerene dissolved or dispersed in the carbohydrate adjuvant.
  • the present invention provides a fullerene dispersion system, which contains fullerene and a carbohydrate auxiliary, and is characterized in that the particle diameter of the dispersion system is mainly at 690-710 nm, such as 50% or more, such as 60%, 70%, 80%, 90%, 95%, and 99% of the particle sizes are located at 690-710nm.
  • the present invention provides a fullerene dispersion system, said system containing fullerene and a carbohydrate auxiliary, characterized in that more than 50%, such as 60%, 70%, 80%, of said dispersion system , 90%, 95%, 99% of the particle size distribution is 690-700nm.
  • the present invention provides a cosmetic or drug delivery system and / or a sustained release system, characterized by comprising a composition or dispersion system according to any one of the preceding claims.
  • the present invention provides a method for preparing a fullerene composition or a dispersion system, characterized in that the method includes the following steps: (1) taking a fullerene powder, a carbohydrate auxiliary powder, and mixing uniformly (2) the mixture is processed by grinding; (3) dissolved by adding water; (4) high-speed centrifugation; (5) filtration; optionally, said step further comprises (6) concentration; (7) drying; optionally, all The finished product obtained in the step (7) may be further dissolved or reconstituted into a desired solution with water; optionally, the degree of dissolution is monitored by ultraviolet absorbance during the grinding treatment; optionally, the grinding is performed by a ball mill, colloid mill, sand Mill or homogenizer, etc .; preferably, the filtration uses a G4 sand core funnel.
  • the present invention provides a fullerene composition, which is prepared by the method of claim 4.
  • the carbohydrate auxiliary is selected from the group consisting of: monosaccharides, disaccharides, oligosaccharides, polysaccharides, glycosamines, etc .; optionally, the monosaccharide is selected from fructose, galactose, glucose; any Optionally, the disaccharide is selected from sucrose, lactose, maltose, melibiose, cellobiose, and the like; optionally, the polysaccharide is selected from celluloses, hyaluronic acids; optionally, the sugar amine
  • the class is selected from the group consisting of acetochitosamine, lactamide, and glucosamine; optionally, the cellulose class is, for example, hydroxyethyl cellulose, ethyl cellulose, microcrystalline cellulose, hydroxypropyl methyl cellulose, formazan Cellulose, etc .; optionally, the hyaluronic acids such as h
  • "approximately” as used herein encompasses all possible values within a range of 10%, preferably 5%, above and below its defined value. For example, about 10, including but not limited to 9, 9.1, 9.2, 9.3, 9.4, 9.5, or 10.1, 10.2, 10.3, 10.4, 10.5, and the like.
  • the fullerene is at least one of hollow fullerene, metal fullerene, heterocyclic fullerene, and embedded fullerene, including but not limited to fullerene C2n, M @ Any of C2n, M2 @ C2n, MA @ C2n, M3N @ C2n, M2C2 @ C2n, M2S @ C2n, M2O @ C2n, and MxA3-xN @ C2n, or a mixture thereof, wherein M and A are metal elements, The M and A are each selected from any one of Sc, Y, and lanthanide metal elements; of 30 genus elements; 00 genus elements, and preferably, the fullerenes are C60, C70, C76, C84, Gd Any one of @ C82 and a derivative thereof or a mixture thereof, and further preferably, the fullerene is C60.
  • the composition is composed of hydroxyethyl cellulose, sodium hyaluronate, glucose, fullerene, and optionally, the ratio of the composition is (10-50): ( 5-20): (30-80): (0.1-10), for example, the ratio is 40: 10: 49: 1, 30: 20: 49: 1, 20: 10: 69: 1, 30: 5: 64: 1,30: 10: 59: 0.1, preferably in a ratio of 30: 10: 59: 1; optionally, the composition may further contain other organic solvents and / or water as a solvent.
  • composition or dispersion system Use of a composition or dispersion system according to any of the preceding aspects in the manufacture of a cosmetic or cosmetic product.
  • composition or dispersion system Use of a composition or dispersion system according to any of the preceding aspects in the preparation of a device for beauty or makeup.
  • the present invention provides a method of cosmetic treatment, the method comprising administering to a subject an effective amount of a composition of the present invention or a medicament comprising the composition of the present invention, optionally, the cosmetic effect comprises At least one of whitening and freckle removing, wrinkle removing, anti-acne, and hair loss prevention.
  • composition of the present invention can also be used with other excipients.
  • composition of the present invention can be used with a surfactant.
  • composition of the invention may be incorporated into a cosmetic or drug delivery system and / or a sustained release system.
  • composition of the present invention as a liquid preparation may be, for example, an aqueous suspension, a solution, or a dry product which can be formulated with water or another suitable carrier before use.
  • This liquid preparation may contain conventional additives such as suspending agents such as sorbitol, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated food fat; solutions Is usually prepared by dissolving the active substance in a carrier, filtering and sterilizing it before filling it into a suitable vial or ampoule, and then sealing it.
  • the present invention provides a method for preparing a fullerene composition: after mixing the fullerene composition of the present invention with water in a desired ratio, stir well, and then homogenize, add a preservative and flavor Get a lotion.
  • composition of the present invention may also be made in the form of an emulsion, and may include a conventional emulsifier, a co-emulsion, a surfactant, and the like.
  • the present invention provides a method for preparing an emulsion of a fullerene composition.
  • the fullerene composition is mixed with an emulsifier according to a ratio, and then homogenized to form an emulsion or paste, and an antiseptic and flavor are added to obtain an emulsion. .
  • the beauty or cosmetic product is used for whitening and removing freckles, wrinkles, anti-acne, haze prevention, hair growth and solid hair.
  • Figure 1 Dynamic light scattering experiment of a fullerene solution, Figure 1A sodium hyaluronate-fullerene, Figure 1B hydroxyethyl cellulose-fullerene, Figure 1C glucose-fullerene, Figure 1D hyaluronic acid- Hydroxyethyl cellulose-glucose-fullerene.
  • Figure 2 This patent composition scavenges hydroxyl radicals
  • Figure 2A is a blank test
  • Figure 2B is a 5 ppm (fullerene content) test group
  • Figure 2C is a 25 ppm (fullerene content) test group
  • Figure 2D is a water-soluble vitamin C 25ppm.
  • Figure 3 Mean MMV test of the patented composition.
  • Figure 5 Testing the effect of the patent composition on the acne-induced inflammatory response.
  • Figure 6 Testing the effect of the patent composition on reducing the erythema area of acne skin (the proportion of erythema area).
  • Fig. 7 Testing the effect of reducing the erythema area of acne skin (rate of erythema area change) of the present patent composition.
  • FIG. 8 Tests the effect of reducing the stain of the patent composition.
  • Fig. 10 Changes in the moisture content of the stratum corneum in the test area (compared to each time point, * p ⁇ 0.05; ** p ⁇ 0.01; *** p ⁇ 0.001).
  • Figure 11 Change rate of cuticle moisture content in the test area, (significant analysis between groups, there are significant differences between different letters).
  • Fig. 13 Change rate of skin fairness L value in test area (significant analysis between groups, there are significant differences between different letters).
  • FIG. 15 The change rate of the skin melanin content MI value in the test area (significant analysis between groups, there are significant differences between different letters).
  • the present invention provides a fullerene composition
  • a fullerene composition comprising a carbohydrate adjuvant and a fullerene dissolved or dispersed in the carbohydrate adjuvant, optionally, said fullerene concentration It is 0.01-5 mg / ml, preferably 0.05-3 mg / ml, more preferably 0.1-2 mg / ml, and still more preferably 1 mg / ml.
  • the composition or dispersion system is composed of hydroxyethyl cellulose, sodium hyaluronate, glucose, fullerene, and optionally, the proportion of the composition is parts by weight (10-50 ): (5-20): (30-80): (0.1-10), for example, the ratio is 40: 10: 49: 1, 30: 20: 49: 1, 20: 10: 69: 1, 30: 5 : 64: 1, 30: 10: 59: 0.1, and the preferred ratio is 30: 10: 59: 1.
  • the composition may further contain other organic solvents and / or water as a solvent, for example, the composition ingredients are hydroxyethyl cellulose, sodium hyaluronate, glucose, fullerene, 1 -3 butanediol and water in a ratio of 6: 2: 11.8: 0.02: 75: 5.18 by weight.
  • the composition ingredients are hydroxyethyl cellulose, sodium hyaluronate, glucose, fullerene, 1 -3 butanediol and water in a ratio of 6: 2: 11.8: 0.02: 75: 5.18 by weight.
  • the present invention provides a method for preparing a fullerene composition or a dispersion system, which is characterized by comprising the following steps: (1) taking a fullerene powder, a carbohydrate additive, and mixing them uniformly; (2) Ball milling composite; (3) Dissolution: fully dissolve the prepared fullerene composite material using deionized water; (4) Centrifugation: centrifuge the dissolved solution at 8500r / min and 5min high speed to remove Large particles that are insoluble in the solution; (5) Filtration: G4 sand core funnel is used to filter out the fine precipitates in the solution; (6) Concentration: The obtained filtrate is subjected to vacuum distillation or a microfiltration membrane to remove the solution Most of the water content; (7) Drying: freeze-drying or spray-drying is used to remove water content to obtain water-soluble fullerene powder.
  • the present invention provides a fullerene composition, which, in addition to a carbohydrate auxiliary and fullerene, contains at least one antioxidant selected from the group consisting of superoxidation Dismutase, mannitol, histidine, tryptophan, bilirubin, quercetin, quercetin, polyphenols, proanthocyanidins, tocotrienols, catechins, catechin derivatives, rutin and Its derivatives, gallic acid and its derivatives, ubiquinone, astaxanthin, carotene, and other carotenoids and their derivatives and their salts, vitamins B and their derivatives and their salts, At least one of vitamin Ds and their derivatives and their salts, vitamin Es and their derivatives and their salts, dibutylhydroxytoluene and butylhydroxyanisole.
  • at least one antioxidant selected from the group consisting of superoxidation Dismutase, mannitol, histidine, tryptophan, bili
  • the present invention provides a fullerene composition, which is characterized by containing, in addition to a carbohydrate adjuvant and fullerene, at least one additional active ingredient, the active ingredient including but Not limited to: Matrix metal elastase inhibitor, melanin synthesis stimulant or inhibitor, whitening or decoloring agent, pro-pigment forming agent, suntan, anti-aging agent, NO-synthase inhibitor, antioxidant, free Base scavengers and / or anti-air pollution agents, anti-glycation agents, emulsifiers, emollients, organic solvents, liquid propellants, skin conditioners such as humectants, substances that retain moisture, alpha hydroxy acids, beta hydroxy acids, moisturizers Agents, epidermal hydrolases, vitamins, pigments or colorants, dyes, gel polymers, thickeners, surfactants, softeners, anti-wrinkle agents, agents that reduce or treat bags under the eyes, exfoliants, anti
  • the present invention provides the use of a fullerene composition in the preparation of a cosmetic or cosmetic product.
  • the cosmetic or cosmetic dosage forms include, but are not limited to, solutions, suspensions, emulsions, creams, gels, creams, emulsions, powders, soaps, surfactant-containing cleaners, oils , Powder foundation cream, lotion, foundation cream, wax-based foundation cream, sprays, tinctures, pastes and plasters, such as creams, complex emulsions, anhydrous compositions, water dispersants, oils, Lotion, balm, foam, lotion, gel, cream gel, hydroalcohol solution, hydrodiol solution, tincture, saline solution, soap, shampoo, conditioner, slurry, ointment, mousse, ointment Agent, powder, stick, pen, spray, aerosol, capsule, gelatin capsule, tablet, sugar-coated tablet, powder, granule form, chewing gum, solution, suspension, emulsion, syrup, polysaccharide film, frozen Gum, gelatin, ointment, cream, softening lotion, nutritional lotion,
  • the present invention provides the use of a fullerene composition in the preparation of a device for cosmetic or cosmetic use, including, but not limited to, a disinfecting wipe, a disinfecting cotton swab, a disinfecting bag, medical Dressing wipes, care fluids, cleaning fluids, dressings, liquid dressings, band-aids; the application can be that the composition of the present invention is attached to a specific material, including but not limited to cotton swabs, wipes, towels, paper towels, gauze , Cotton swabs, non-woven fabrics, polymer materials, medical dressings, non-stick gauze for plastic models, petrolatum gauze, semi-permeable membranes, foaming accessories, etc.
  • composition of the present invention can also be used with other excipients, which include hyaluronic acid, oils and fats, surfactants, preservatives, perfumes, adhesives, thickeners, complexing agents, PH regulator.
  • excipients include hyaluronic acid, oils and fats, surfactants, preservatives, perfumes, adhesives, thickeners, complexing agents, PH regulator.
  • composition of the present invention can be used with a surfactant selected from the group consisting of: anionic surfactants, cationic surfactants, amphoteric surfactants, lipophilic nonionic surfactants, At least one of an aqueous nonionic surfactant and a natural surfactant.
  • a surfactant selected from the group consisting of: anionic surfactants, cationic surfactants, amphoteric surfactants, lipophilic nonionic surfactants, At least one of an aqueous nonionic surfactant and a natural surfactant.
  • examples of the anionic surfactant include soap raw materials, fatty acid soaps such as sodium laurate, sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate, and polyoxyethylene.
  • (POE) -alkyl ether sulfates such as lauryl triethanolamine, POE-sodium lauryl sulfate, N-acyl sarcosine such as sodium lauroyl sarcosinate, N-myristoyl-N-methyl taurine
  • Higher fatty acid amide sulfonates such as sodium, coconut oil fatty acid sodium methyl taurate, sodium lauryl methyl taurine, phosphate salts such as POE-olealkenyl ether phosphate, POE-stearyl ether phosphate, Sulfosuccinates such as sodium di-2-ethylhexylsulfosuccinate, monolauroylmonoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, linear dodecyl Alkylbenzene sulfonates such as sodium besylate, linear dodecylbenzene
  • examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride, and distearyldimethyl chloride.
  • Ammonium dialkyldimethylammonium salts poly (N, N'-dimethyl-3,5-methylenepiperidinium chloride), alkylpyridinium salts such as cetylpyridinium chloride, Alkyl quaternary ammonium salts, alkyl dimethyl benzyl ammonium salts, alkyl isoquinolinium salts, dialkyl morpholinium salts, POE-alkylamines, alkylamine salts, polyamine fatty acid derivatives, pentyl At least one of an alcohol fatty acid derivative, benzalkonium chloride, and benzethonium chloride.
  • examples of the amphoteric surfactant include 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2 -Imidazoline hydroxide 1-carboxyethoxy disodium salt and other imidazoline amphoteric surfactants, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryl At least one of betaine-type amphoteric surfactants such as betaine dimethylaminoacetic acid betaine, alkylbetaine, amidobetaine, and sulfobetaine.
  • examples of the lipophilic nonionic surfactant include sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, and sorbitan.
  • examples of the hydrophilic nonionic surfactant include POE-sorbitan monooleate, POE-sorbitan monostearate, and POE-sorbitan monooleate.
  • POE-sorbitan fatty acid esters such as esters, POE-sorbitan tetraoleate, POE-sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan penta POE-sorbitan fatty acid esters such as oleate, POE-sorbitol monostearate, POE-glycerol monostearate, POE-glycerol monoisostearate, POE-glycerol triisostearate POE-glycerin fatty acid esters such as esters, POE-monooleate, POE-distearate, POE-mono-dioleate, ethylene glycol distearate and other POE-fatty acid esters, POE- POE-alkyl ethers
  • POE.POP-Cetyl ether POE.POP-2-decyltetradecyl ether, POE.POP-monobutyl ether, POE.POP-hydrogenated lanolin, POE.POP-glyceryl ether and other POE.POP-alkanes Ethers
  • POE-castor oil POE-hardened castor oil
  • POE- POE such as castor oil monoisostearate, POE-hardened castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearate diester, POE-hardened castor oil maleic acid and other POEs -Castor oil-hardened castor oil derivatives
  • POE-Sorbitol beeswax and other POE-beeswax lanolin derivatives coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide and other alkanol
  • examples of the natural surfactant include at least one of lecithins such as soybean phospholipid, hydrogenated soybean phospholipid, egg yolk phospholipid, and hydrogenated egg yolk phospholipid, or soybean saponin.
  • the composition of the invention may be added to a cosmetic or drug delivery system and / or a slow release system, said cosmetic or drug delivery system and / or a slow release system is selected from the group consisting of: liposomes , Mixed liposomes, millimeter microcapsules, microcapsules, nanomicrocapsules, sponges, cyclodextrins, vesicles, micelles, surfactant mixed micelles, phospholipid-surfactant mixed micelles, millimeter microspheres, micro Spheres, nanomicrospheres, lipid microspheres, microemulsions, nanoemulsions, millimeter particles, particles, nanoparticles and solid lipid nanoparticles.
  • the composition of the present invention in the form of a liquid formulation may be, for example, an aqueous suspension, a solution, or a dry product that can be formulated with water or other suitable carriers before use.
  • This liquid preparation may contain conventional additives such as suspending agents such as sorbitol, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated food fat; solutions Is usually prepared by dissolving the active substance in a carrier, filtering and sterilizing it before filling it into a suitable vial or ampoule, and then sealing it.
  • the present invention provides a method for preparing a fullerene composition.
  • the fullerene composition of the present invention is mixed with water according to a ratio, stirred uniformly, and then homogenized, and a preservative and Fragrance gets water.
  • the composition of the present invention is in the form of an emulsion and may include conventional emulsifiers, emulsifiers, surfactants, and the like.
  • the present invention provides a method for preparing an emulsion of a fullerene composition.
  • the fullerene composition of the present invention is mixed with an emulsifier according to a ratio, and then homogenized to form an emulsion or paste. Preservatives and flavors give emulsions.
  • the invention provides the use of a composition or dispersion system of the invention in the preparation of a cosmetic or cosmetic product.
  • the invention provides the use of a composition or dispersion system of the invention in the preparation of a device for beauty or makeup.
  • Example 1 Compounding of hydroxyethyl cellulose, sodium hyaluronate and glucose with fullerene:
  • the UV detection absorbance A value gradually increases, indicating that the fullerene content in the water-soluble composition gradually increases and the recombination rate gradually increases, but when the ball milling reaches 12h, the fullerenes increase.
  • the content is lower than that of ball milling for 10h, which indicates that when the ball milling time is too long, the solubility of the water-soluble composition is reduced, and the fullerene content in the corresponding aqueous solution is reduced.
  • the ball milling compound for 10h no precipitation occurs, and it can be completely dissolved. .
  • the UV detection absorbance A value gradually increases, indicating that the fullerene content in the water-soluble composition gradually increases, and the recombination rate gradually increases.
  • the fullerene content It is slightly higher than the ball milling for 10 hours.
  • the G4 sand core funnel is filtered to obtain a water-soluble fullerene material.
  • the UV detection absorbance A value gradually increases, indicating that the fullerene content in the water-soluble composition gradually increases, and the recombination rate gradually increases.
  • the fullerene content It is slightly higher than the ball milling for 10 hours.
  • the G4 sand core funnel is filtered to obtain a water-soluble fullerene material.
  • Centrifugation Centrifuge the dissolved solution at 8500r / min and 5min at high speed to remove large particles that are not dissolved in the solution;
  • the G4 sand core funnel is used to filter out the fine precipitates in the solution
  • Drying Freeze-drying or spray-drying to remove water to obtain water-soluble fullerene powder.
  • the raw materials in the following table were formulated into a 0.1% aqueous solution, and centrifuged at 4000 r / min for 15 minutes (refer to General Principle 0123 of the Pharmacopoeia) to test the stability of the liquid.
  • Example 5 The spin capture method was used to test the ability of the patent composition to scavenge hydroxyl radicals under different concentration conditions
  • Figure 2A is a blank test
  • Figure 2B is a 5 ppm (fullerene content) experimental group
  • Figure 2C is a 25 ppm (fullerene content) experimental group
  • Figure 2D is a water-soluble vitamin C at 25 ppm.
  • Skin moisture content tester Corneometer 825 Courage + Khakaza Cologne Germany.
  • MMV skin moisture content
  • TEWL transepidermal water loss
  • the skin moisture content was measured on the inner side of the elbow of 30 subjects before the application of different raw material essences and after 1h, 2h, and 4h, and the average MMV was calculated. The results are shown in Figure 3.
  • Volunteers' acne clinical performance was graded according to the acne Pillsbury4 and Cunliffe12 classification.
  • the enrolled subjects were divided into three groups according to the grading results, namely level 1 (mild), level 2 (moderate), and level 3 (severe) acne subjects.
  • the facial image analysis system VISIA was applied -CR collects the image of the subject's face, and obtains a facial erythema image under cross-polarized light. The subject's inflammatory response and acne growth can be observed. The darker the color in the image, the stronger the skin inflammatory response.
  • the rate of change in the proportion of skin erythema area of subjects with grade 1 (mild), grade 2 (moderate), and grade 3 (severe) acne is negative at each time point;
  • test sample can significantly reduce the proportion of skin erythema area, and has obvious effects on alleviating skin inflammation and acne.
  • mice were anesthetized with 2.5% sodium pentobarbital, the model group was intramuscularly injected with 0.4% progesterone injection at a dose of 0.02 g / kg to the hind limbs of the mice 6 times a week for 4 weeks.
  • the normal group was sterilized with water for injection at 0.02 g / kg.
  • Sixty healthy female mice were randomly divided into 6 groups of 3 dose groups, 10 in each group.
  • Normal group, model group, and one group of fullerene compositions (hydroxyethyl cellulose, sodium hyaluronate, glucose, and fullerene mass ratio of 30: 10: 59: 1) for external application in three dose groups (0.1%, 0.2%, 0.3%), 3% hydroquinone positive control group (0.69 mg / ml).
  • a group of 3 dose treatment groups were administered topically to the skin on the day of mouse modeling, once a day for 30 consecutive days.
  • the normal group and the model group were given topical application of distilled water at the corresponding time; the 3% hydroquinone positive drug control group started the topical application on the day of modeling, the time and course of treatment were the same as the fullerene group.
  • mice Thirty days after the administration, mice were sacrificed by cervical dislocation, and their backs were depilated. Two pieces of liver tissue and two pieces of skin tissue from the application site were quickly taken. One of them was rinsed with ice-cold physiological saline to remove the blood. The filter paper was drained and the liver and skin were excised. Each 0.5g was put into a beaker of 2.0ml pre-cooled normal saline, the tissue was cut, and then poured into a test tube, homogenized twice with a high-speed disperser 10r / min for 10 seconds each time; and then 3500r / rain Centrifuge for 15 minutes at speed and take the supernatant for testing.
  • the normal group was unmodeled, the model group was treated with drugs after modeling, and the positive group was hydroquinone known to have excellent whitening effect.
  • the number of melanocytes in the model group increased significantly, the number of dermal inflammatory cells increased, and the number of dermal blood vessels decreased.
  • the number of melanocytes and dermatitis cells were higher than the model group.
  • Low the number of dermal blood vessels increased significantly, indicating a certain whitening effect and a certain concentration dependence.
  • the composition of the present invention has significant effects on the model group and the positive control group, and the composition of the present invention has a whitening and freckle removing effect.
  • the patented fullerene composition (wherein the mass ratio of hydroxyethyl cellulose, sodium hyaluronate, glucose, and fullerene is 30: 10: 59: 1) is treated for 5 days on the skin explants, and then exposed to a polluted environment in.
  • the results showed that the state of the skin cells treated with the ingredients of this patent was almost the same as that of the blank group.
  • the skin damaged by the haze showed a marked increase in damaged cells, and the results are shown in FIG. 9.
  • Example 10 Skin whitening, anti-wrinkle and hydration effect test
  • Blank matrix group (hereinafter referred to as sample group 1): water, glycerol, EDT-2Na, butanediol, carbomer, xanthan gum, sodium hyaluronate, hydroxyethyl cellulose, glucose, glyceryl stearate, Cetylstearyl alcohol, cyclopentadimethylsiloxane, phenoxyethanol, ethylhexyl glycerol (wherein the mass ratio of hydroxyethyl cellulose, sodium hyaluronate, and glucose is 30:10:59)
  • sample group 2 water, glycerin, EDT-2Na, butanediol, carbomer, xanthan gum, sodium hyaluronate, hydroxyethyl cellulose, glucose, stearic acid glyceride , Cetylstearyl alcohol, cyclopentadimethylsiloxane, fullerene, phenoxyethanol, ethylhexyl glycerol (wherein the mass ratio of hydroxyethyl cellulose, sodium hyaluronate, glucose, and fullerene is 30: 10: 59: 1, the added amount of the patent composition is 0.15%)
  • Positive control group water, glycerol, EDT-2Na, butanediol, carbomer, xanthan gum, sodium hyaluronate, hydroxyethyl cellulose, glucose, glyceryl stearate, Cetylstearyl alcohol, cyclopentadimethylsiloxane, vitamin C, acetylhexapeptide-8, phenoxyethanol, ethylhexyl glycerol (among them hydroxyethyl cellulose, sodium hyaluronate, glucose mass ratio 30:10:59, vitamin C added 3%, acetylhexapeptide-8 added 3%)
  • sample group 4 Water, glycerol, EDT-2Na, butanediol, carbomer, xanthan gum, sodium hyaluronate, hydroxyethyl cellulose, glucose, glyceryl stearate, Cetylstearyl alcohol, cyclopentadimethylsiloxane, fullerene, vitamin C, acetylhexapeptide-8, phenoxyethanol, ethylhexyl glycerol (of which hydroxyethyl cellulose, sodium hyaluronate , Glucose, fullerene mass ratio is 30: 10: 59: 1, the added amount of the patent composition, vitamin C, acetylhexapeptide-8 is 0.075%, 3%, 3%)
  • Corneometer moisture content tester Corneometer German C & K, CM 825;
  • the change rate is the relative change rate before use.
  • the calculation formula is as follows:
  • T 0 skin index data of the test area before using the sample
  • T n skin index data of the test area after using the sample
  • the skin wrinkle depth improvement effect of each sample group was ranked as follows: sample 4 group> sample 2 group> sample 3 group> sample 1 group; Among them, there was no significant difference between sample 2 group, sample 3 group, and sample 4 group; the effect of sample 2 group, sample 3 group, and sample 4 group was significantly better than that of sample 1 group (p ⁇ 0.05)

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Abstract

一种水溶性富勒烯外用组合物及制备方法和应用，含有水溶性助剂以及在水溶性助剂中溶解或分散的富勒烯，具有美容的效果。

Description

一种水溶性富勒烯外用组合物 技术领域
本发明涉及一种日化领域，特别涉及一种具有美容作用的外用组合物。
背景技术
1985年科学家Kroto、Smalley、Curl等人在研究太空深处的碳元素时发现了C60富勒烯，1996年三人因此而获得诺贝尔化学奖。富勒烯与金刚石、石墨同为碳的同素异形体。C60是由60个碳原子组成的球形分子，由12个五边形和20个六边形组成，每个碳原子和相邻的三个碳原子通过SP 2杂化成键，因形似足球而被称为CITE。具有笼状碳原子团簇结构的系列分子被统称为分子被统称为有笼Note><Cite><Au烯衍生物及杂环富勒烯等。常见的C60、C70、C76、C84等种类。
富勒烯的多个P轨道构成的大π键共轭体系，使得其具有较强的接受电子的能力，因其独特的结构和理化性质，使其具有优异的清除自由基性能，被称为“自由基海绵”，同时还表现出了优异的抗氧化性能。使其在化妆品材料、生物医药等方面得到广泛关注。
通过将C60嵌入表面活性剂中，C60仍可以消除细胞内的活性氧，抑制线粒体的去极化、半胱氨酸蛋白酶的激活、细胞膜上磷脂酰丝氨酸的曝光以及DNA的分裂，C60表现出了保护细胞不被氧化凋亡的作用。C60脂质体复合物通过防御UVA对皮肤结构，细胞核和胶原纤维的破坏以及向人体皮肤组织的渗透来起到抗氧化作用，是维他命C的172倍，能够亲和自由基。
Fathi Moussa教授长期从事C60的性质研究工作，作为将富勒烯溶于橄榄油中进行研究的第一人，他们通过对老鼠10-17个月每两周喂一次(每公斤体重喂4毫克富勒烯)，对照组老鼠17-38个月死亡，而试验组寿命则延长至59-66个月，发现富勒烯具有长寿保健功能。期间无论体重，生理表现无一异常，并未发现C60具有毒性和生物遗传性，相反一定量的C60具有清除自由基性能，从而使动物免受过多自由基产生的危害。
作为外用品，已有专利报道了富勒烯相关的产品，例如C60-PVP，申请号：200480005008.1，200580049615.2，由于制备工艺及PVP与C60的复合特性限制，在该复合物中，C60的含量不超过1％，加之PVP有明显的成膜性，过多的涂敷在皮肤表层后对某些化妆品功效的发挥会起到一定的阻碍作用。C60-角鲨烷，申请号201510427642.4，但是C60在角鲨烷中的溶解度有限，同时角鲨烷是油溶液，使得该系列产品的使用受限。富勒烯纳米悬浮液CN201510971343.7，但是该成分为大颗粒的富勒烯成分，添加到配方中后会影响配方稳定性和外观及使用舒适度，并且大颗粒的富勒烯成分很难在皮肤起到修复作用，仅能附着在皮肤表层，起到屏障作用。
富勒烯是一种非极性分子，具有强烈的疏水性，仅能够溶于对生物体有害的非极性有机溶剂如甲苯、苯、环己烷、氯仿中。富勒烯本身疏水性性质直接影响了其生物活性的发挥，为了更好的促进吸收，将富勒烯制成易于皮肤快速吸收其呈分子状态的溶液型，将富勒烯复配皮肤亲善型的成分还没有被研究过。本发明得到的水溶性富勒烯原料均为团簇性质，在水溶液中均匀透明，稳定不沉降。所选辅料不存在表面活性剂性质，不会对皮肤产生刺激作用，对皮肤的修复和保湿作用良好。该组合物中富勒烯的含量高，功效更佳明显。本发明专利发明的含富勒烯的组合物，确保了富勒烯良好地分散于所选溶剂中，得到的含富勒烯的组合物性质稳定，可用于任何外用配方。本发明的组合物中富勒烯是溶解状态，作为外用产品成分，可以更好的作用于皮肤。
发明内容
本发明的目的在于提供一种富勒烯组合物，该组合物中富勒烯呈现溶解状态，且快速吸收，具有保湿、锁水、抗氧化等美容效果。
在一方面，本发明提供了一种富勒烯组合物，其含有碳水化合物助剂以及在碳水化合物助剂中溶解或分散的富勒烯。
在一方面，本发明提供了一种富勒烯分散体系，所述体系含有富勒烯和碳水化合物助剂，其特征在于所述分散体系粒径主要位于690-710nm，例如50％以上，例如60％、70％、80％、90％、95％、99％以上的粒径位于690-710nm。
在一方面，本发明提供了一种富勒烯分散体系，所述体系含有富勒烯和碳水化合物助剂， 其特征在于所述分散体系中50％以上，例如60％、70％、80％、90％、95％、99％以上的粒径分布在690-700nm。
在一方面，本发明提供了化妆品或药物递送系统和/或缓释系统，其特征在于包含根据前述权利要求任一项的组合物或分散体系。
在一方面，本发明提供了一种富勒烯组合物或者分散体系的制备方法，其特征在于，所述方法包括如下步骤：(1)取富勒烯粉末，碳水化合物助剂粉末，混合均匀；(2)混合物通过研磨处理；(3)加水溶解；(4)高速离心；(5)过滤；任选地，所述步骤还包括(6)浓缩；(7)干燥；任选地，所述步骤(7)获得的成品可以进一步用水溶解或重构成需要的溶液；任选地，所述研磨处理时，通过紫外吸光度监测溶解程度；任选地，所述研磨通过球磨机、胶体磨、砂磨或均质机等进行；优选地，所述过滤采用G4砂芯漏斗。
在一方面，本发明提供了一种富勒烯组合物，其特征在于，采用权利要求4的方法制备。
根据前述任一方面，所述碳水化合物助剂选自：单糖、二糖、低聚糖、多糖、糖胺类等；任选地，所述单糖选自果糖、半乳糖、葡萄糖；任选地，所述二糖选自蔗糖、乳糖、麦芽糖、蜜二糖、纤维二糖等；任选地，所述多糖选自纤维素类、透明质酸类；任选地，所述糖胺类选自乙酰壳糖胺、乳酰胺、葡糖胺；任选地，所述纤维素类例如羟乙基纤维素、乙基纤维素、微晶纤维素、羟丙基甲基纤维素、甲基纤维素等；任选地，所述透明质酸类例如透明质酸、透明质酸钠、透明质酸钾、水解透明质酸、水解透明质酸钠等；优选地，所述碳水化合物助剂为羟乙基纤维素、透明质酸钠、葡萄糖中的至少一种，更优选地，所述碳水化合物助剂为羟乙基纤维素、透明质酸钠、葡萄糖；任选地，所述碳水化合物助剂与富勒烯的重量比为(20-200):1，优选(50-200):1，进一步优选(70-150)：1，例如大约50:1、60:1、70:1、80:1、90:1、100:1、110:1、120:1、130:1、140:1、150:1、160:1、170:1、180:1、190:1、200:1。无特殊指明的情况下，本文中出现的“大约”涵盖在其限定的数值上下偏离10％，优选5％的范围内所有可能的数值。例如约10，包括但不限于9、9.1、9.2、9.3、9.4、9.5或者10.1、10.2、10.3、10.4、10.5等。
根据前述任一方面，所述富勒烯为空心富勒烯、金属富勒烯、杂环富勒烯和内嵌富勒烯中的至少一种，包括但不限于富勒烯C2n、M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2n和MxA3-xN@C2n中的任一种或其混合物，其中，M和A均为金属元素，所述M和A均选自Sc、Y和镧系金属元素中的任意一种；30属元素中的；00属元素，优选地，所述富勒烯为C60、C70、C76、C84，Gd@C82及其衍生物中的任意一种或其混合物，进一步优选地，所述富勒烯为C60。
根据前述任一方面，其特征在于所述组合物由羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯组成，任选地，所述组合物的比例为(10-50)：(5-20)：(30-80)：(0.1-10)，例如比例为40：10：49：1，30：20：49：1，20：10：69：1，30：5：64：1，30:10:59:0.1，优选比例为30：10：59：1；任选地，所述组合物还可以进一步含有其他有机溶剂和/或水作为溶剂。
根据前述任一方面的组合物或分散体系在制备美容或化妆用品中的用途。
根据前述任一方面的组合物或分散体系在制备用于美容或化妆的器械中的用途。
根据前述任一方面，本发明提供一种美容的方法，所述方法包括向受试者施用有效量的本发明的组合物或包含本发明组合物的药剂，任选地，所述美容效果包括美白祛斑，祛皱，抗痘，防脱固发的至少一种。
根据前述任一方面，本发明组合物还可以与其他辅料一起使用。
根据前述任一方面，本发明组合物可以与表面活性剂一起使用。
根据前述任一方面，本发明组合物可以被加入到化妆品或药物递送系统和/或缓释系统中。
本发明组合物作为液体制剂的形式例如可以是水性悬浮液、溶液剂，还可以是一种在使用前可用水或其它适宜的载体复配的干燥产品。这种液体制剂可含有常规的添加剂，诸如悬浮剂，例如山梨醇、甲基纤维素、明胶、羟乙基纤维素、羧甲基纤维素、硬脂酸铝凝胶或氢化食用脂肪；溶液剂的制备通常是通过将活性物质溶解在一种载体中，并在将其装入一种适 宜的小瓶或安瓿前过滤消毒，然后密封。
在一方面，本发明提供一种富勒烯组合物制备水剂方法：将本发明的富勒烯组合物按照所需比例与水混合后，搅拌均匀，然后均质好，加入防腐剂和香精得到水剂。
本发明组合物也可以制成乳剂的形式，可包含常规的乳化剂，助乳剂、表面活性剂等。
在一方面，本发明提供一种富勒烯组合物制备乳剂方法：将富勒烯组合物按照比例与乳化剂混合，然后进行均质，成乳状液或膏体，加入防腐剂和香精得到乳剂。
根据前述任一方面，所述美容或化妆用品用于美白祛斑，祛皱，抗痘，防霾，生发固发等。
附图说明
图1：富勒烯溶液的动态光散射实验，图1A透明质酸钠-富勒烯，图1B羟乙基纤维素-富勒烯，图1C葡萄糖-富勒烯，图1D透明质酸-羟乙基纤维素-葡萄糖-富勒烯。
图2：本专利组合物清除羟基自由基，图2A为空白试验，图2B为5ppm(富勒烯含量)实验组，图2C为25ppm(富勒烯含量)试验组，图2D为水溶性维生素C 25ppm。
图3：测试本专利组合物的MMV均值。
图4：测试本专利组合物的TEWL均值。
图5：测试本专利组合物的缓解痤疮炎症反应效果。
图6：测试本专利组合物的减少痤疮皮肤红斑面积效果(红斑面积占比)。
图7：测试本专利组合物的减少痤疮皮肤红斑面积效果(红斑面积变化率)。
图8：测试本专利组合物的淡化色斑效果。
图9：本专利组合物的防霾实验。
图10测试区域角质层水分含量变化趋势(各时间点比较，*p<0.05；**p<0.01；***p<0.001)。
图11测试区域角质层水分含量变化率,(组间显著性分析，不同字母间存在显著性差异)。
图12测试区域皮肤白皙度L值变化趋势(各时间点比较，*p<0.05；**p<0.01；***p<0.001)。
图13测试区域皮肤白皙度L值变化率(组间显著性分析，不同字母间存在显著性差异)。
图14测试区域皮肤黑色素含量MI值变化趋势(各时间点比较，*p<0.05；**p<0.01；***p<0.001)。
图15测试区域皮肤黑色素含量MI值变化率(组间显著性分析，不同字母间存在显著性差异)。
图16测试区域皮肤弹性Q1值变化趋势(各时间点比较，*p<0.05；**p<0.01；***p<0.001)。
图17测试区域皮肤弹性Q1值变化率(组间显著性分析，不同字母间存在显著性差异)
图18测试区域皮肤皱纹深度变化趋势(各时间点比较，*p<0.05；**p<0.01；***p<0.001)。
图19测试区域皮肤皱纹深度变化率(组间显著性分析，不同字母间存在显著性差异)。
具体实施方式
下面结合附图，对本发明的具体实施方式进行详细描述，但应当理解本发明的保护范围并不受具体实施方式的限制。
除非另有其它明确表示，否则在整个说明书和权利要求书中，术语“包括”或其变换如“包含”或“包括有”等等将被理解为包括所陈述的元件或组成部分，而并未排除其它元件或其它组成部分。
在一个实施方案中，本发明提供了一种富勒烯组合物，其含有碳水化合物助剂以及在碳水化合物助剂中溶解或分散的富勒烯，任选地，所述的富勒烯浓度为0.01-5mg/ml，优选0.05-3mg/ml，更优选0.1-2mg/ml，进一步优选1mg/ml。
在一个实施方案中，所述组合物或分散体系由羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯组成，任选地，所述组合物的比例为重量份数(10-50)：(5-20)：(30-80)：(0.1-10)，例如比例为40：10：49：1，30：20：49：1，20：10：69：1，30：5：64：1，30:10:59:0.1， 优选比例为30：10：59：1。
在一个实施方案中，所述组合物还可以进一步含有其他有机溶剂和/或水作为溶剂，例如，所述组合物成分为羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯、1-3丁二醇、水，比例为重量份数6：2：11.8：0.02：75：5.18。
在一个实施方案中，本发明提供了一种富勒烯组合物或者分散体系的制备方法，其特征在于，包括如下步骤：(1)取富勒烯粉末，碳水化合物助剂，混合均匀后；(2)球磨复合；(3)溶解：将制备得到的富勒烯复合材料，使用去离子水进行充分溶解；(4)离心：将溶解得到的溶液，经过8500r/min，5min高速离心，去除溶液中不溶解的大颗粒；(5)过滤：再使用G4砂芯漏斗，滤除溶液中细微沉淀物；(6)浓缩：将得到的滤液使用减压旋蒸或采用微滤膜，去除溶液中大部分水分；(7)干燥：采用冷冻干燥或喷雾干燥去除水分，得到水溶性富勒烯粉末。
在一个实施方案中，本发明提供了一种富勒烯组合物，其特征在于，除了碳水化合物助剂和富勒烯之外，还含有至少一种抗氧化剂，所述抗氧化剂选自超氧化物歧化酶、甘露醇、组氨酸、色氨酸、胆红素、槲皮黄素、槲皮苷、多酚、原花青素、生育三烯酚、儿茶酸、儿茶酸衍生物、芦丁及其衍生物、五倍子酸及其衍生物、泛醌、虾青素、胡萝卜素、以及其他的类胡萝卜素类物质及其衍生物和它们的盐、维生素B类及其衍生物和它们的盐、维生素D类及其衍生物和它们的盐、维生素E类及其衍生物和它们的盐、二丁基羟基甲苯以及丁基羟基苯甲醚中的至少一种。
在一个实施方案中，本发明提供了一种富勒烯组合物，其特征在于，除了碳水化合物助剂和富勒烯之外，还含有至少一种另外的活性成分，所述活性成分包括但不限于：基质金属弹性蛋白酶抑制剂，黑素合成刺激剂或抑制剂，增白剂或脱色剂，色素原形成剂，仿晒剂，抗老化剂，NO-合酶抑制剂，抗氧化剂，自由基清除剂和/或抗大气污染剂，抗糖化剂，乳化剂，润肤剂，有机溶剂，液体推进剂，皮肤调节剂如湿润剂、保留水分的物质、α羟基酸、β羟基酸、保湿剂、表皮水解酶、维生素、色素或着色剂，染料，凝胶聚合物，增厚剂，表面活性剂，软化剂，抗皱剂，能够减少或治疗眼袋的药剂，去角质剂，抗微生物剂，杀真菌剂，抑真菌剂，杀细菌剂，抑细菌剂，真皮或表皮大分子合成刺激剂和/或能够阻止或抑制真皮或表皮大分子降解的药剂，胶原蛋白合成刺激剂，弹性蛋白合成刺激剂，核心蛋白多糖合成刺激剂，层粘连蛋白合成刺激剂，防御素合成刺激剂，分子伴侣合成刺激剂，水通道蛋白合成刺激剂，透明质酸合成刺激剂，脂质和角质层的组分合成刺激剂，神经酰胺合成刺激剂，胶原蛋白降解抑制剂，弹性蛋白降解抑制剂，成纤维细胞增殖刺激剂，角质形成细胞增殖刺激剂，脂肪细胞增殖刺激剂，黑素细胞增殖刺激剂，角质形成细胞分化刺激剂，脂肪细胞分化刺激剂，乙酰胆碱酯酶抑制剂，皮肤弛缓剂，糖胺聚糖合成刺激剂，DNA修复剂，DNA保护剂，止痒剂，用于治疗和/或护理敏感皮肤的药剂，固化剂，抗萎缩纹剂，收敛剂，调节皮脂产生的药剂，脂肪分解刺激剂，抗蜂窝组织炎剂，愈合刺激剂，愈合辅助佐剂，上皮再形成刺激剂，上皮再形成辅助佐剂，细胞因子生长因子，镇静剂，抗炎剂，作用于毛细管循环和/或微循环的药剂，血管生成刺激剂，血管通透性抑制剂，作用于细胞代谢的药剂，用于改善真皮-表皮接合的药剂，促进毛发生长的药剂，抑制或延缓毛发生长的药剂，防腐剂，芳香剂，螯合剂，植物提取物，精油，海洋提取物，来自生物发酵过程的药剂，矿物盐，细胞提取物和遮光剂(针对紫外线A和/或紫外线B起作用的有机的或矿物的光保护剂)，或其混合物。
在一个实施方案中，本发明提供一种富勒烯组合物在制备美容或化妆用品中的应用。
在一个实施方案中，所述美容或化妆用品剂型包括但不限于溶液、悬浮液、乳浊液、膏剂、凝胶剂、霜剂、乳液、粉剂、皂、含表面活性剂的清洁剂、油、粉末粉底霜、乳液、粉底霜、蜡基粉底霜、喷剂、搽剂、糊剂和泥敷剂中的任意剂型,例如乳膏剂、复合乳剂、无水组合物、水分散剂、油、乳液、香脂、泡沫、洗液、凝胶、乳膏凝胶、水醇溶液、水二醇溶液、搽剂、盐水溶液、肥皂、洗发剂、调节剂、浆液、油膏、摩丝、软膏剂、粉剂、棒剂、笔剂、喷雾剂、气雾剂、胶囊剂、明胶胶囊、片剂、糖衣片剂、粉剂、颗粒形式、口香糖、溶液、悬浮液、乳剂、糖浆、多糖膜、冻胶、明胶、软膏、霜剂、柔软化妆水、营养化妆水、面膜、精华素、生发剂、洗发剂、漂洗剂、护发素、头发护理剂、凝胶剂、皮肤乳液、皮肤 柔软剂、爽肤水、收敛剂、乳液、牛奶乳液、保湿乳液、营养乳液、按摩霜、营养霜、保湿霜、护手霜、粉底霜、营养精华、防晒霜、皂、清洁泡沫、清洁乳、清洁霜、身体乳液以及身体清洁剂、眼袋去除剂、化妆粉底、卸妆洗液、卸妆乳液、眼影、口红、唇彩和唇粉；所述美容或化妆用品的功效包括但不限于：肌肤美白、改善色素沉淀、治疗粉刺、改善皱纹、改善皮肤粗糙、改善油性皮肤、改善干燥肌肤、收缩毛孔、治疗疤痕、治疗面色潮红、治疗脱发、促进生发、治疗烧伤、皮肤杀菌、皮肤杀螨、改善皮肤凹坑、抗痘、防霾中的至少一种。
在一个实施方案中，本发明提供一种富勒烯组合物在制备用于美容或化妆用途的器械中的应用，所述器械包括但不限于，消毒擦片、消毒棉棒、消毒包、医用敷料湿巾、护理液、清洗液、敷料、液体敷料、创可贴；所述应用可以是本发明组合物附着于特定材料上，所述材料包括但不限于：棉签、湿巾、毛巾、纸巾、纱布、棉棒、无纺布、高分子材料、医用敷料、塑料模型不沾纱布、凡士林油纱布、半通透性膜、泡沫性辅料等。
在一个实施方案中，本发明组合物还可以与其他辅料一起使用，所述辅料包括透明质酸、油脂类、表面活性剂、防腐剂、香料、粘合剂、增稠剂、络合剂、PH调节剂。
在一个实施方案中，本发明组合物可以与表面活性剂一起使用，所述表面活性剂选自：阴离子表面活性剂、阳离子表面活性剂、两性表面活性剂、亲油性非离子表面活性剂、亲水性非离子表面活性剂、天然系表面活性剂中的至少一种。
在一个实施方案中，作为阴离子表面活性剂，例如可以列举皂用原料、月桂酸钠、棕榈酸钠等脂肪酸皂，月桂基硫酸钠、月桂基硫酸钾等高级烷基硫酸酯盐，聚氧乙烯(POE)-月桂基硫酸三乙醇胺、POE-月桂基硫酸钠等烷基醚硫酸酯盐，月桂酰肌氨酸钠等N-酰基肌氨酸，N-肉豆蔻酰基-N-甲基牛磺酸钠、椰子油脂肪酸甲基牛磺酸钠、月桂基甲基牛磺酸钠等高级脂肪酸酰胺磺酸盐，POE-油烯基醚磷酸钠、POE-硬脂酰醚磷酸等磷酸酯盐，二-2-乙基己基磺基琥珀酸钠、单月桂酰基单乙醇酰胺聚氧乙烯磺基琥珀酸钠、月桂基聚丙二醇磺基琥珀酸钠等磺基琥珀酸盐，直链十二烷基苯磺酸钠、直链十二烷基苯磺酸三乙醇胺、直链十二烷基苯磺酸等烷基苯磺酸盐，N-月桂酰基谷氨酸单钠、N-硬脂酰基谷氨酸二钠、N-肉豆蔻酰基-L-谷氨酸单钠等N-酰基谷氨酸盐，硬化椰子油脂肪酸甘油硫酸钠等高级脂肪酸酯硫酸酯盐，土耳其红油等硫酸化油，POE-烷基醚羧酸、POE-烷基烯丙基醚羧酸盐、α酸烯烃磺酸盐、高级脂肪酸酯磺酸盐、仲醇硫酸酯盐、高级脂肪酸烷基醇酰胺硫酸酯盐、月桂酰单乙醇酰胺琥珀酸钠、N-棕榈酰天冬氨酸二三乙醇胺以及酪蛋白钠等中的至少一种。
在一个实施方案中，作为阳离子表面活性剂，例如可以列举硬脂基三甲基氯化铵、月桂基三甲基氯化铵等烷基三甲基铵盐，二硬脂基二甲基氯化铵二烷基二甲基铵盐，氯化聚(N，N’-二甲基-3，5-亚甲基哌啶鎓)、氯化鲸蜡基吡啶鎓等烷基吡啶鎓盐，烷基季铵盐、烷基二甲基苄基铵盐、烷基异喹啉鎓盐、二烷基吗啉鎓盐、POE-烷基胺、烷基胺盐、聚胺脂肪酸衍生物、戊醇脂肪酸衍生物、苯扎氯铵以及苄索氯铵等中的至少一种。
在一个实施方案中，作为两性表面活性剂，例如可以列举2-十一烷基-N，N，N-(羟乙基羧甲基)-2-咪唑啉钠、2-椰油基-2-咪唑啉氢氧化物-1-羧乙氧基二钠盐等咪唑啉系两性表面活性剂，2-十七烷基-N-羧甲基-N-羟乙基咪唑啉鎓甜菜碱、月桂基二甲基氨基乙酸甜菜碱、烷基甜菜碱、酰胺基甜菜碱以及磺基甜菜碱等甜菜碱系两性表面活性剂等中的至少一种。
在一个实施方案中，作为亲油性非离子表面活性剂，例如可以列举脱水山梨糖醇单油酸酯、脱水山梨糖醇单异硬脂酸酯、脱水山梨糖醇单月桂酸酯、脱水山梨糖醇单棕榈酸酯、脱水山梨糖醇单硬脂酸酯、脱水山梨糖醇倍半油酸酯、脱水山梨糖醇三油酸酯、五-2-乙基己酸二甘油脱水山梨糖醇酯、四-2-乙基己酸二甘油脱水山梨糖醇酯等脱水山梨糖醇脂肪酸酯类，单棉籽油脂肪酸甘油酯、单芥酸甘油酯、倍半油酸甘油酯、单硬脂酸甘油酯、α，α’-油酸焦谷氨酸甘油酯、单硬脂酸甘油酯等脂肪酸甘油酯类，单异硬脂酸二甘油酯、二异硬脂酸二甘油酯等聚甘油脂肪酸酯，单硬脂酸丙二醇酯等丙二醇脂肪酸酯类、硬化蓖麻油衍生物以及甘油烷基醚等中的至少一种。
在一个实施方案中，作为亲水性非离子表面活性剂，例如可以列举POE-脱水山梨糖醇单油酸酯、POE-脱水山梨糖醇单硬脂酸酯、POE-脱水山梨糖醇单油酸酯、POE-脱水山梨糖醇四油酸酯等POE-脱水山梨糖醇脂肪酸酯类，POE-山梨糖醇单月桂酸酯、POE-山梨糖 醇单油酸酯、POE-山梨糖醇五油酸酯、POE-山梨糖醇单硬脂酸酯等POE-山梨糖醇脂肪酸酯类，POE-甘油单硬脂酸酯、POE-甘油单异硬脂酸酯、POE-甘油三异硬脂酸酯等POE-甘油脂肪酸酯类，POE-单油酸酯、POE-二硬脂酸酯、POE-单二油酸酯、二硬脂酸乙二醇酯等POE-脂肪酸酯类，POE-月桂基醚、POE-油烯基醚、POE-硬脂酰醚、POE-山萮酰醚、POE-2-辛基十二烷基醚、POE-胆甾烷醇醚等POE-烷基醚类，POE.POP-鲸蜡醚、POE.POP-2-癸基四癸醚、POE.POP-单丁醚、POE.POP-氢化羊毛脂、POE.POP-甘油醚等POE.POP-烷基醚类，POE-蓖麻油、POE-硬化蓖麻油、POE-硬化蓖麻油单异硬脂酸酯、POE-硬化蓖麻油三异硬脂酸酯、POE-硬化蓖麻油单焦谷氨酸单异硬脂酸二酯、POE-硬化蓖麻油马来酸等POE-蓖麻油硬化蓖麻油衍生物、POE-山梨糖醇蜂蜡等POE-蜂蜡·羊毛脂衍生物，椰子油脂肪酸二乙醇酰胺、月桂酸单乙醇酰胺、脂肪酸异丙醇酰胺等烷醇酰胺，POE-丙二醇脂肪酸酯、POE-烷基胺、POE-脂肪酸酰胺、蔗糖脂肪酸酯、POE-壬基苯基甲醛缩合物、烷基乙氧基二甲基氧化胺以及三油烯基磷酸等中的至少一种。
在一个实施方案中，作为天然系表面活性剂，例如可以列举大豆磷脂、氢化大豆磷脂、卵黄磷脂、氢化卵黄磷脂等卵磷脂类或大豆皂角素等中的至少一种。
在一个实施方案中，本发明组合物可以被加入到化妆品或药物递送系统和/或缓释系统中，所述化妆品或药物递送系统和/或缓释系统选自由以下组成的组：脂质体、混合脂质体、毫米微胶囊、微胶囊、纳米微胶囊、海绵、环糊精、囊泡、胶束、表面活性剂混合胶束、磷脂-表面活性剂混合胶束、毫米微球、微球、纳米微球、脂微球、微乳剂、纳米乳剂、毫米微粒、微粒、纳米微粒和固体脂质纳米微粒。
在一个实施方案中，本发明组合物作为液体制剂的形式例如可以是水性悬浮液、溶液剂，还可以是一种在使用前可用水或其它适宜的载体复配的干燥产品。这种液体制剂可含有常规的添加剂，诸如悬浮剂，例如山梨醇、甲基纤维素、明胶、羟乙基纤维素、羧甲基纤维素、硬脂酸铝凝胶或氢化食用脂肪；溶液剂的制备通常是通过将活性物质溶解在一种载体中，并在将其装入一种适宜的小瓶或安瓿前过滤消毒，然后密封。
在一个实施方案中，本发明提供了一种富勒烯组合物制备水剂方法：将本发明的富勒烯组合物按照比例与水混合后，搅拌均匀，然后均质好，加入防腐剂和香精得到水剂。
在一个实施方案中，本发明组合物制成乳剂的形式，可包含常规的乳化剂，助乳剂、表面活性剂等。
在一个实施方案中，本发明提供了一种富勒烯组合物制备乳剂方法：将本发明的富勒烯组合物按照比例与乳化剂混合，然后进行均质，成乳状液或膏体，加入防腐剂和香精得到乳剂。
在一个实施方案中，本发明提供本发明的组合物或分散体系在制备美容或化妆用品中的用途。
在一个实施方案中，本发明提供本发明的组合物或分散体系在制备用于美容或化妆的器械中的用途。
实施例
下面参照实施例进一步阐释本发明。对本发明的具体示例性实施方案的描述是为了说明和例证的目的。这些描述并非想将本发明限定为所公开的精确形式，并且很显然，根据本申请说明书的教导，可以进行很多改变和变化。对示例性实施例进行选择和描述的目的在于解释本发明的特定原理及其实际应用，从而使得本领域的技术人员能够实现并利用本发明的各种不同的示例性实施方案以及各种不同的选择和改变。
实施例1：羟乙基纤维素、透明质酸钠和葡萄糖与富勒烯复合：
1)、使用羟乙基纤维素对富勒烯进行球磨复合
A、不同球磨时间，不同时间点取样，称取0.1g羟乙基纤维素：富勒烯组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000001
Figure PCTCN2019090926-appb-000002
总结：相同投料比的情况下，随球磨时间的增加，紫外检测吸光度A数值逐渐增大，说明水溶性组合物中富勒烯含量逐渐增加，复合率逐渐提升，但球磨达到12h时，富勒烯含量比球磨10h低，说明当球磨时间过长后，导致水溶性组合物溶解性降低，相应的水溶液中富勒烯含量随之降低，通过高速离心后，球磨复合10h，无沉淀产生，能够全部溶解。
B、相同球磨时间10h，不同投料比，秤取0.1g组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000003
总结：相同球磨时间，不同质量比的情况下，随富勒烯质量的增加，复合产物颜色逐渐加深；水溶性逐渐降低；离心后沉淀物逐渐增加。
2)、使用透明质酸钠对富勒烯进行球磨复合
A、不同球磨时间，不同时间点取样，秤取0.1g透明质酸钠：富勒烯组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000004
总结：相同投料比的情况下，随球磨时间的增加，紫外检测吸光度A数值逐渐增大，说明水溶性组合物中富勒烯含量逐渐增加，复合率逐渐提升，球磨达到12h时，富勒烯含量比球磨10h略高，通过高速离心后，G4砂芯漏斗过滤，得到水溶性富勒烯材料。
B、相同球磨时间12h，不同投料比，秤取0.1g组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000005
总结：相同球磨时间，不同投料比的情况下，随富勒烯质量的增加，离心后沉淀量逐渐增加，上层清液颜色较浅；G4砂芯过滤，滤液基本无色，说明随富勒烯质量的增加，最终得到的水溶性材料溶解性降低。
3)、使用葡萄糖对富勒烯进行球磨复合
A、不同球磨时间，不同时间点取样，秤取0.1g葡萄糖：富勒烯组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000006
Figure PCTCN2019090926-appb-000007
总结：相同投料比的情况下，随球磨时间的增加，紫外检测吸光度A数值逐渐增大，说明水溶性组合物中富勒烯含量逐渐增加，复合率逐渐提升，球磨达到12h时，富勒烯含量比球磨10h略高，通过高速离心后，G4砂芯漏斗过滤，得到水溶性富勒烯材料。
B、相同球磨时间12h，不同投料比，秤取0.1g组合物，缓慢加入到80ml去离子水中，溶解搅拌30min。
Figure PCTCN2019090926-appb-000008
总结：相同球磨时间，不同投料比的情况下，随富勒烯质量的增加，离心后沉淀量逐渐增加，上层清液颜色较浅；G4砂芯过滤，滤液基本无色，说明随富勒烯质量的增加，最终得到的水溶性材料溶解性降低。
4)、复配水溶性富勒烯组合物材料制备过程
制备方式——羟乙基纤维素、透明质酸钠、葡萄糖混合后与富勒烯粉末进行复合
球磨复合时间：10h
水溶性富勒烯材料处理过程
溶解：将制备得到的富勒烯复合材料，使用去离子水进行充分溶解
离心：将溶解得到的溶液，经过8500r/min，5min高速离心，去除溶液中不溶解的大颗粒；
过滤：再使用G4砂芯漏斗，滤除溶液中细微沉淀物；
浓缩：将得到的滤液使用减压旋蒸或采用微滤膜，去除溶液中大部分水分；
干燥：采用冷冻干燥或喷雾干燥去除水分，得到水溶性富勒烯粉末。
实施例3、动态光散射-检测水溶液中材料的粒径
将表中原料配制成0.1％的水溶液，利用动态光散射测试粒径。结果如图1所示。
原料名称 DLS平均粒径nm
羟乙基纤维素-富勒烯 740
透明质酸钠-富勒烯 730
葡萄糖-富勒烯 670
羟乙基纤维素：透明质酸钠：葡萄糖-富勒烯 738
实施例4、高速离心测试几种原料的稳定性
将以下表格中原料配制成0.1％的水溶液，离心机4000r/min离心15分钟(参照药典第一部通则0123)，测试液体稳定性。
原料名称 稳定性
羟乙基纤维素-富勒烯 无沉淀
透明质酸钠-富勒烯 有沉淀
葡萄糖-富勒烯 有沉淀
羟乙基纤维素-透明质酸钠-葡萄糖-富勒烯 无沉淀
实施例5、自旋捕获法测试不同浓度条件下本专利组合物清除羟基自由基的能力
20uL的0.1mol/L DMPO和20uL0.03mol/L的H 2O 2水溶液中加入5uL一定浓度的样品，由紫外光激发双氧水产生羟基自由基，通过检测esr信号变化，分析组合物清除羟基自由基的效果。结果如图2所示。图2A为空白试验，图2B为5ppm(富勒烯含量)实验组， 图2C为25ppm(富勒烯含量)试验组，图2D为水溶性维生素C 25ppm.从图2A-C中可以看出，相同浓度的富勒烯和维生素C，富勒烯清除羟基自由基的能力要更加优异。
实施例6、保湿补水性能测试
皮肤水分含量测试仪：Corneometer 825 Courage+Khakaza Cologne Germany。
皮肤水分散失测试仪：TM300 Courage+Khakaza Cologne Germany。
由测试得到的皮肤水分含量(MMV)值和经表皮水分散失(TEWL)值，来判定原料保湿锁水性能(MMV 25-35一般，35-45中等，45-55良好，大于55优秀；TEWL 11-12一般，12-13中等，13-14良好，大于14优秀)
待测样品配制：
将表格中原料配制成质量分数为0.5％的水溶液
Figure PCTCN2019090926-appb-000009
对照：为涂抹任何护肤产品的空白
测定30名受试者肘部内侧在涂抹添加不同原料精华液前和涂抹1h、2h和4h后皮肤水分含量，计算MMV均值，结果见图3。
从图3中可以看出本专利组合物的保湿性能更加优异，在第4h时依然保持良好的保湿性能。将羟乙基纤维素、透明质酸钠、葡萄糖复配后与富勒烯复合比以上原料单独与富勒烯复合效果更好，本专利组合物最优比例的效果较其他比例的更好。
测定30名受试者在涂抹添加不同原料精华液前和涂抹1h、2h和4h后，皮肤水分散失量，计算TEWL均值，结果见图4。由图4可以看出本专利组合物对于皮肤水分的保持更有优势。
实施例7祛痘实验
根据痤疮pillsbury4、Cunliffe12分级法对志愿者的痤疮临床表现情况进行分级。入组受试者按照分级结果分为三组，即1级(轻度)、2级(中度)和3级(重度)痤疮受试者.在测试周期14天内，应用面部图像分析系统VISIA-CR对受试者面部进行图像采集，在交叉偏振光下得到面部红斑图像，可观察受试者炎症反应程度和痤疮生长情况，图像中颜色越深，表示皮肤炎症反应程度越强。
在测试周期14天内，通过VISIA-CR对受试者使用样品前后进行图像采集，3级(重度)痤疮受试者(编号34)图像对比结果见图5。
由图5看出，在测试周期14天内，3级(重度)痤疮受试者(编号34)使用测试样 品14天后，VISIA-CR自然光图像和红斑图像中被红圈标记出来的痤疮生长区域颜色逐渐变浅，发红区域面积缩小，痤疮周围的炎症反应下降，较小和部分较大的痤疮基本消失，以上说明，测试样品具有缓解皮肤炎症反应和祛痘的效果。
如图6所示，在测试周期14天内，使用测试样品后，1级(轻度)、2级(中度)和3级(重度)痤疮受试者皮肤红斑面积占比在各时间点均低于使用前，且1级(轻度)痤疮受试者皮肤红斑面积占比在第7天和第14天时存在显著性差异(p<0.05)，2级(中度)和3级(重度)痤疮受试者皮肤红斑面积占比在在各时间点时存在显著性差异(p<0.05)。
如图7所示，1级(轻度)、2级(中度)和3级(重度)痤疮受试者皮肤红斑面积占比变化率在各时间点时均为负值；
以上说明，测试样品可以显著降低皮肤红斑面积占比，缓解皮肤炎症反应和祛痘的效果明显。
实施例8：美白实验
实验方法：将小鼠用2.5％戊巴比妥钠麻醉后，模型组以0.4％的黄体酮注射液按0.02g/kg剂量小鼠后肢肌肉注射，每周6次，连续4周。正常组按0.02g/kg肌肉注射灭菌注射用水。取健康雌性小鼠60只，3个剂量组，随机分为6组，每组lO只。正常组、模型组、一组富勒烯组合物(羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯质量比为30：10：59：1)外用3个剂量组(0.1％、0.2％、0.3％)、3％氢醌阳性对照组(0.69mg/ml)。一组3个剂量治疗组分别在小鼠造模当日皮肤局部外用给药，每日1次，连续用药30天。正常组和模型组于相应时间给予蒸馏水局部涂抹；3％氢醌阳性药对照组于造模当日开始局部用药，时间和疗程同富勒烯组。给药30天后，颈椎脱臼处死小鼠，背部去毛，迅速取肝组织及涂药部位的皮肤组织各2块，其中一块用冰冷的生理盐水冲洗，除去血液，滤纸吸干，切取肝脏及皮肤各0.5g，分别放入2.0ml预冷生理盐水的烧杯中，剪碎组织，再倒人试管中，以高速分散器lO r/min匀浆两次，每次10秒；再以3500r/rain转速离心15分钟，取上清液，进行测试。
结果：如下表
Figure PCTCN2019090926-appb-000010
结论：如上表所示，正常组为未造模，模型组为造模后为进行药物处理，阳性组为已知具有优良美白效果的氢醌。造模成功后，模型组的黑素细胞数明显增多，真皮炎症细胞数增多，真皮血管数减少，对比低、中、高三个给药组发现其黑素细胞数量、真皮炎细胞均比模型组低，真皮血管数明显增加，说明都有一定的美白效果，并且有一定的浓度依赖关系。本发明组合物对于模型组、阳性对照组具有显著功效，本发明的组合物具有美白祛斑的作用。
添加有本发明专利组合物0.2％的面霜，给予志愿者试用。志愿者入选条件：
①入组33例，有效人数30例，35～60岁，男、女均可；
②医疗和健康状况符合纳入标准；
③无化妆品过敏史；
④治疗前2周未服用皮质类固醇激素、抗生素、维A酸类药物或接受其他抗痤疮药 物治疗；
⑤近2年内未做过激光美容或化学换肤；
⑥无伦理学禁忌；
图8中可以看出，在使用含有本专利发明组合物0.2％的产品6周后，脸颊处黑色素明显减少，皮肤亮度显著提高
实施例9：防霾实验
将本专利富勒烯组合物(其中羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯质量比为30：10：59：1)处理皮肤外植体5天，然后暴露于污染环境中。结果显示经过本专利成分处理的皮肤细胞状态与空白组几乎没有差别。而被雾霾损伤过的皮肤表现出受损细胞明显增多，结果如图9所示。
实施例10：皮肤美白抗皱补水效果测试
待测样品：空白基质组、本专利组、阳性对照组、复配组
空白基质组(以下简称样品1组)：水、甘油、EDT-2Na、丁二醇、卡波姆、黄原胶、透明质酸钠、羟乙基纤维素、葡萄糖、硬脂酸甘油脂、鲸蜡硬脂醇、环五聚二甲基硅氧烷、苯氧乙醇、乙基己基甘油(其中羟乙基纤维素、透明质酸钠、葡萄糖质量比为30：10：59)
本专利组分组(以下简称样品2组)：水、甘油、EDT-2Na、丁二醇、卡波姆、黄原胶、透明质酸钠、羟乙基纤维素、葡萄糖、硬脂酸甘油脂、鲸蜡硬脂醇、环五聚二甲基硅氧烷、富勒烯、苯氧乙醇、乙基己基甘油(其中羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯质量比为30：10：59：1，该专利组合物添加量为0.15％)
阳性对照组(以下简称样品3组)：水、甘油、EDT-2Na、丁二醇、卡波姆、黄原胶、透明质酸钠、羟乙基纤维素、葡萄糖、硬脂酸甘油脂、鲸蜡硬脂醇、环五聚二甲基硅氧烷、维生素C、乙酰基六肽-8、苯氧乙醇、乙基己基甘油(其中羟乙基纤维素、透明质酸钠、葡萄糖质量比为30：10：59，维生素C添加量为3％，乙酰基六肽-8添加量为3％)
复配组(以下简称样品4组)：水、甘油、EDT-2Na、丁二醇、卡波姆、黄原胶、透明质酸钠、羟乙基纤维素、葡萄糖、硬脂酸甘油脂、鲸蜡硬脂醇、环五聚二甲基硅氧烷、富勒烯、维生素C、乙酰基六肽-8、苯氧乙醇、乙基己基甘油(其中羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯质量比为30：10：59：1，该专利组合物、维生素C、乙酰基六肽-8添加量分别为0.075％、3％、3％)
1、测试仪器：
角质层水分含量测试仪Corneometer(德国C&K,CM 825)；
皮肤色差测试探头及多探头皮肤测试系统(德国C&K,CL 400&MPA 10)；
皮肤弹性测试仪(德国C&K,Cutometer dual MPA580)；
皮肤黑色素和血红素测试仪(德国C&K,Mexameter MX 18)；
面部图像分析系统VISIA-CR(美国Canfield)；
皮肤快速光学成像系统Derma TOP
2、入选标准：
1)身体健康的中国人群，性别随机，年龄35-55岁
2)面部肌肤暗黄，肤色28°<ITA°<45°
3)近2年内未做过激光美容或化学换肤
4)医疗和健康状况符合纳入标准
5)既往对护肤类化妆品无过敏史
6)无伦理学禁忌
7)在研究前已阅读并在知情同意书上签字
8)测试期间受试者不得使用与样品功能相似的化妆品
3、洗脱期
测试前一天，受试部位未使用与样品功效相似的化妆品。
4、测试部位
脸颊，眼角。
5、测试人数
有效受试者60人，年龄49.03±1.55岁(均值±SE)
6、数据分析
应用SPSS软件进行统计学分析，如果数据呈正态分布，应用配对t检验的方法分析测试样品使用前后皮肤数据的变化以及样品2组与对照组间的差异。如果数据呈非正态分布，应用秩和检验进行相应统计分析。根据上述统计分析结果做出测试样品是否有效的结论，双侧检验，检验水准α＝0.05。
变化率即相对使用前的变化率，计算公式如下：
Figure PCTCN2019090926-appb-000011
式中，T 0——使用样品前受试区皮肤指标数据
T n——使用样品后受试区皮肤指标数据
n——回访时间
7、统计学测试结果
如图10和11所示，受试者使用测试产品后在第2周、4周、6周时间点，各样品组角质层水分含量的提升效果排序为：样品2组＞样品4组＞样品3组＞样品1组；其中，样品2组、样品3组、样品4组无显著性差异；样品2组、样品3组、样品4组效果显著好于样品1组(p<0.05)。
如图12和13所示，受试者使用测试产品后在第2周、4周、6周时间点，各样品组皮肤白皙度L值的提升效果排序为：样品4组＞样品2组＞样品3组＞样品1组；其中，样品2组、样品3组、样品4组无显著性差异；样品2组、样品3组、样品4组效果显著好于样品1组(p<0.05)。
如图14和15所示，受试者使用测试产品后在第2周时间点，各样品组皮肤黑色素含量MI值的改善效果排序为：样品2组＞样品4组＞样品3组＞样品1组；其中，样品2组、样品3组、样品4组无显著性差异；样品2组、样品3组、样品4组效果显著好于样品1组(p<0.05)
如图16和17所示，受试者使用测试产品后在第4周、6周时间点，各样品组皮肤弹性Q1值的提升效果排序为：样品4组＞样品2组＞样品3组＞样品1组；其中，样品2组、样品3组、样品4组效果显著优于样品1组(p<0.05)
如图18和19所示，受试者使用测试产品后在第2周时间点，各样品组皮肤皱纹深度的改善效果排序为：样品4组＞样品2组＞样品3组＞样品1组；其中，样品2组、样品3组、样品4组无显著性差异；样品2组、样品3组、样品4组效果显著好于样品1组(p<0.05)
临床数据显示：纯富勒烯组效果明显，同时富勒烯有使维生素C及肽类效果增强的作用。

Claims (10)

  1. 一种富勒烯组合物，其含有碳水化合物助剂以及在助剂中溶解或分散的富勒烯，任选地，所述组合物以粉末形式或者溶液形式。
  2. 一种富勒烯分散体系，所述体系含有富勒烯和碳水化合物助剂，其特征在于所述分散体系中50％以上，例如60％、70％、80％、90％、95％、99％以上的粒径分布在690-700nm。
  3. 化妆品或药物递送系统和/或缓释系统，其特征在于包含根据前述权利要求任一项的组合物或分散体系。
  4. 一种富勒烯组合物或者分散体系的制备方法，其特征在于，所述方法包括如下步骤：(1)取富勒烯粉末，碳水化合物助剂粉末，混合均匀；(2)混合物通过研磨处理；(3)加水溶解；(4)高速离心；(5)过滤；任选地，所述步骤还包括(6)浓缩；(7)干燥；任选地，所述步骤(7)获得的成品可以进一步用水溶解或重构成需要的溶液；任选地，所述研磨处理时，通过紫外吸光度监测溶解程度；任选地，所述研磨通过球磨机、胶体磨、砂磨或均质机等进行；优选地，所述过滤采用G4砂芯漏斗。
  5. 一种富勒烯组合物，其特征在于，采用权利要求4的方法制备。
  6. 根据前述权利要求任一项的组合物或分散体系或方法，所述碳水化合物助剂选自：单糖、二糖、低聚糖、多糖、糖胺类等；任选地，所述单糖选自果糖、半乳糖、葡萄糖；任选地，所述二糖选自蔗糖、乳糖、麦芽糖、蜜二糖、纤维二糖等；任选地，所述多糖选自纤维素类、透明质酸类；任选地，所述糖胺类选自乙酰壳糖胺、乳酰胺、葡糖胺；任选地，所述纤维素类例如羟乙基纤维素、乙基纤维素、微晶纤维素、羟丙基甲基纤维素、甲基纤维素等；任选地，所述透明质酸类例如透明质酸、透明质酸钠、透明质酸钾、水解透明质酸、水解透明质酸钠等；优选地，所述碳水化合物助剂为羟乙基纤维素、透明质酸钠、葡萄糖中的至少一种，更优选地，所述碳水化合物助剂为羟乙基纤维素、透明质酸钠、葡萄糖；任选地，所述碳水化合物助剂与富勒烯的重量比为50-200:1。
  7. 根据前述权利要求任一项的组合物或分散体系或方法，所述富勒烯为空心富勒烯、金属富勒烯、杂环富勒烯和内嵌富勒烯中的至少一种，包括但不限于富勒烯C 2n、M@C 2n、M 2@C 2n、MA@C 2n、M 3N@C 2n、M 2C 2@C 2n、M 2S@C 2n、M 2O@C 2n和M xA 3-xN@C 2n中的任一种或其混合物，其中，M和A均为金属元素，所述M和A均选自Sc、Y和镧系金属元素中的任意一种；30属元素中的；00属元素，优选地，所述富勒烯为C60、C70、C76、C84，Gd@C82及其衍生物中的任意一种或其混合物，进一步优选地，所述富勒烯为C60。
  8. 根据前述权利要求任一项的组合物或分散体系，其特征在于所述组合物或分散体系由羟乙基纤维素、透明质酸钠、葡萄糖、富勒烯组成，任选地，所述组合物的比例为(10-50)：(5-20)：(30-80)：(0.1-10)，例如比例为40：10：49：1，30：20：49：1，20：10：69：1，30：5：64：1，30:10:59:0.1，优选比例为30：10：59：1；任选地，所述组合物还可以进一步含有其他有机溶剂和/或水作为溶剂。
  9. 前述权利要求任一项的组合物或分散体系在制备美容或化妆用品中的用途。
  10. 前述权利要求任一项的组合物或分散体系在制备用于美容或化妆的器械中的用途。
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CN113430073A (zh) * 2021-06-05 2021-09-24 焦点生物医药有限公司 一种富勒烯手工皂的制备方法
CN115198558A (zh) * 2021-07-27 2022-10-18 北京华熙海御科技有限公司 含有透明质酸钠的组合物及其应用
CN115198558B (zh) * 2021-07-27 2024-01-23 北京华熙海御科技有限公司 含有透明质酸钠的组合物及其应用
CN114306185A (zh) * 2021-12-31 2022-04-12 广州市瑞芬化妆品有限公司 抗光变色组合物及其制备方法、美白抗皱精华液及其制备方法
CN114306185B (zh) * 2021-12-31 2023-06-27 广州市瑞芬化妆品有限公司 抗光变色组合物及其制备方法、美白抗皱精华液及其制备方法
CN115006313A (zh) * 2022-07-11 2022-09-06 北京富乐喜科技有限公司 一种含富勒烯的美白保湿凝胶面膜及其制备方法
CN115006313B (zh) * 2022-07-11 2023-08-22 北京富乐喜科技有限公司 一种含富勒烯的美白保湿凝胶面膜及其制备方法

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