WO2022142669A1 - 抗衰老中药组合物及其制备方法和非治疗目的用途以及制备化妆品的用途 - Google Patents

抗衰老中药组合物及其制备方法和非治疗目的用途以及制备化妆品的用途 Download PDF

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WO2022142669A1
WO2022142669A1 PCT/CN2021/127252 CN2021127252W WO2022142669A1 WO 2022142669 A1 WO2022142669 A1 WO 2022142669A1 CN 2021127252 W CN2021127252 W CN 2021127252W WO 2022142669 A1 WO2022142669 A1 WO 2022142669A1
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extract
chinese medicine
traditional chinese
weight
medicine composition
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PCT/CN2021/127252
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English (en)
French (fr)
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孙懿
陈默
赵亚
李玲玉
祝乐
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上海家化联合股份有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236—Ligusticum (licorice-root)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/62—Nymphaeaceae (Water-lily family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • 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
    • A61P17/18—Antioxidants, e.g. antiradicals
    • 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
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Definitions

  • the invention relates to the field of natural medicinal chemistry and cosmetics, in particular to a traditional Chinese medicine composition with anti-aging effect, a preparation method and application of the traditional Chinese medicinal composition.
  • Non-enzymatic glycosylation of NEG is a series of complex non-enzymatic reactions in which reducing sugars are directly combined with protein residues to produce Schiff bases (Schiff), which are cleaved to glucosamine rearrangement (Amadori) products, followed by dehydration, cyclic It is further degraded into a series of reactive aldehyde and ketone compounds (reactive carbonyl compounds RCS).
  • RCS has higher activity than reducing sugars, and can quickly combine with free amino groups of proteins to eventually generate irreversible brown-yellow fluorescent substances, which are collectively referred to as advanced glycation end products (AGEs). ).
  • Human skin tissue contains a large amount of collagen and elastin. These two proteins are metabolized slowly and contain more lysine and hydroxylysine, which provide the material basis for NEG reaction. Skin proteins and reducing sugars generate NEG to form AGEs, which increase with age. With the progressive increase of AGEs, collagen forms intermolecular cross-links, which not only reduces the permeability of connective tissue, but also weakens the diffusion properties of nutrients and wastes, and increases tissue ductility and hardness; it reduces the solubility of collagen and is difficult to be absorbed by collagen Enzymatic hydrolysis results in decreased skin elasticity and wrinkles, which deepen with age.
  • Oxidation is a crucial step in the formation of AGEs.
  • the intermediate products formed by AEGs—active carbonyl groups are all derived from the oxidative degradation or auto-oxidation of Amadori products.
  • AGEs can directly reduce the activity of antioxidant enzymes in the body. Increase skin oxidative stress levels. Overall, oxidative stress can promote the NEG process, and AGEs can increase the level of oxidative stress.
  • many antioxidants have been confirmed to have anti-glycation activity, such as: ascorbic acid, tocopherol, sodium selenite, riboflavin, zinc, manganese, etc.
  • a mixture of green tea, vitamin C (VC), vitamin E (VE), acetylcysteine, and rutin can inhibit the non-enzymatic glycation of collagen in mouse skin.
  • AGEs are: carboxymethyl lysine (CML), carboxyethyl lysine (CEL), pentoside, glycosylated collagen, pyrrolidine and dilysyl imidazoline derivatives Wait. Most of them have fluorescence specificity (such as pentosides, glycosylated limbs), and some do not have fluorescent properties (such as CML, CEL). Therefore, the most typical evaluation of anti-glycation efficacy is to use biochemical reaction methods, that is, to use models such as bovine serum albumin-glucose (BSA-glucose) and bovine serum albumin-pyruvaldehyde (BSA-MGO) to evaluate by fluorescence spectrophotometry.
  • BSA-glucose bovine serum albumin-glucose
  • BSA-MGO bovine serum albumin-pyruvaldehyde
  • the present invention unexpectedly found that the traditional Chinese medicine composition comprising the extracts of saffron, ginseng, lotus, Polygonum cuspidatus, Chuanxiong and Angelica has excellent antioxidant and good anti-glycation effects.
  • the present invention provides an anti-aging traditional Chinese medicine composition, which comprises:
  • the saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract, and Angelica extract are prepared by solvent ultrasonic extraction.
  • the weight ratio of the saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract, and angelica extract is 0.1-0.5:1-3:1-2: 0.5-2:1-2:1-2. In a more preferred embodiment, the weight ratio of the saffron extract, ginseng extract, lotus extract, Polygonum cuspidatum extract, Chuanxiong extract, and Angelica extract is 0.1:3:2:2:1:1 .
  • the extract of the present invention is extracted with ethanol, preferably 70% ethanol by volume.
  • the present invention also relates to the application of a traditional Chinese medicine composition comprising saffron extract, ginseng extract, lotus extract, polygonum extract, chuanxiong extract, and angelica extract for non-therapeutic purposes against skin aging.
  • a traditional Chinese medicine composition comprising saffron extract, ginseng extract, lotus extract, polygonum extract, chuanxiong extract, and angelica extract for non-therapeutic purposes against skin aging.
  • the anti-aging of the skin is achieved by anti-oxidation and/or anti-glycosylation.
  • the present invention also relates to the application of a traditional Chinese medicine composition comprising saffron extract, ginseng extract, lotus extract, polygonum extract, chuanxiong extract, and angelica extract in the preparation of cosmetics for anti-aging skin .
  • the anti-aging of the skin is achieved by anti-oxidation and/or anti-glycosylation.
  • the present invention also relates to a preparation method of a traditional Chinese medicine composition comprising saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract, and Angelica sinensis extract, the method comprising:
  • the saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and Angelica sinensis extract were prepared by solvent ultrasonic extraction method;
  • the saffron extract, the ginseng extract, the lotus flower extract, the Polygonum cuspidatum extract, the Chuanxiong extract and the angelica extract were combined according to parts by weight.
  • the present invention provides an external preparation for skin comprising a traditional Chinese medicine composition of saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and Angelica sinensis extract.
  • the external preparation for skin comprises 0.01-5% by weight of the traditional Chinese medicine composition.
  • Figure 1 shows the results of the relative expression levels of advanced glycation end products (AGEs).
  • BC represents blank control
  • NC represents negative control
  • PC represents positive control.
  • Figure 2 shows the results of immunohistochemical detection.
  • the microscope used was OLMPUS BX53, and the magnifications were 20x objective ⁇ 10x eyepiece and 40x objective ⁇ 10x eyepiece.
  • the picture of expression analysis is the picture of 40x objective lens ⁇ 10x eyepiece.
  • anti-aging includes alleviating, reducing, preventing, improving or eliminating the presence of, for example, fine lines and wrinkles, loss of elasticity, skin unevenness, red scars and age spots.
  • wrinkles include fine lines, micro wrinkles, or coarse wrinkles.
  • wrinkles include, but are not limited to, fine lines around the eyes (eg, "crow's feet"), forehead and cheek wrinkles, brow lines, and laugh lines around the mouth.
  • loss of elasticity includes loss of elasticity or structural integrity of skin or tissue, including but not limited to sagging, sagging, and loose tissue. Loss of elasticity or tissue structural integrity can be caused by a variety of factors including, but not limited to, disease, aging, hormonal changes, mechanical trauma, environmental damage, or as a result of the application of products such as cosmetic or pharmaceuticals to the tissue.
  • skin unevenness refers to a skin condition associated with diffuse or mottled hyperpigmentation, which may be classified as hyperpigmentation, such as post-inflammatory hyperpigmentation.
  • red scar refers to a skin condition associated with redness or erythema.
  • age spots refers to skin conditions associated with discontinuous pigmentation, such as small areas of darker pigmentation that can develop on the face and hands.
  • cosmetic refers to a cosmetic substance or article that maintains, restores, imparts, stimulates, or enhances the appearance of the body, or appears to enhance beauty or rejuvenation, particularly as it relates to the appearance of tissue or skin.
  • a “cosmetically effective amount” refers to an amount of a physiologically active compound or composition sufficient to treat one or more signs of skin aging, but sufficiently low to avoid serious side effects.
  • the cosmetically effective amount of a compound or composition will vary with the specific condition being treated, the age and physical condition of the end user, the severity of the condition being treated/prevented, the duration of the treatment, the nature of the other treatment, The particular compound or product/composition employed, the particular cosmetically acceptable carrier employed, and the like.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises saffron extract.
  • Saffron the stigma of Crocus sativus L. of the Iridaceae family. Aliases are saffron, saffron and so on. Sexual sweet, flat. Heart, liver meridian. It has the effect of promoting blood circulation and removing blood stasis, dispersing depression and opening knots. Modern research shows that saffron has antioxidant, anticoagulant and immune regulation effects.
  • saffron extract Although the application of saffron extract is disclosed in the prior art, the efficacy of saffron extract is not disclosed, and the efficacy and application of the compound extract containing saffron in the present invention are not disclosed.
  • CN110812299A discloses a toner containing saffron and its preparation process.
  • CN106821932A discloses a cosmetic containing saffron extract, which does not disclose the efficacy of saffron extract.
  • CN110279640A discloses that saffron extract has a whitening effect.
  • the traditional Chinese medicine composition of the present invention comprises 1-10 parts by weight, preferably 1-2 parts by weight of saffron extract.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises ginseng extract.
  • Ginseng the root of Panax ginseng C.A.Mey. Also known as yellow ginseng, jade essence, blood ginseng, baby ginseng and so on. Sweet, lukewarm. Returns the lung, spleen, heart and kidney meridians. It has the effect of invigorating vitality and rejuvenating the mind. It has been reported in the literature that the main components of ginseng and its preparations are ginsenosides, which have significant promoting effects in improving learning ability and facilitation of memory, and can also inhibit Staphylococcus aureus and improve autoimmunity. Not only that, ginseng also has antioxidant, anti-aging and anti-inflammatory effects.
  • CN110787075A is a skin care oil composition containing ginseng root extract and ginseng seed oil, wherein the efficacy of ginseng root or ginseng seed oil is not disclosed.
  • the traditional Chinese medicine composition of the present invention comprises 15-40 parts by weight, preferably 15-35 parts by weight of ginseng extract.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises lotus flower extract.
  • the lotus is the bud of Nelumbo nucifera Gaertn. Also known as hanli, hibiscus, hibiscus. Bitter, sweet, flat. Return to the liver and stomach meridians. Lotus can disperse blood stasis and stop bleeding, dispel dampness and eliminate wind.
  • the lotus is rich in flavonoids, which are good antioxidants and bacteriostatic agents. The lotus flavonoids can clear superoxide anion free radicals and hydroxyl free radicals.
  • lotus actives are disclosed in the prior art, lotus, especially the efficacy of lotus/lotus extract, and the efficacy and application of the compound extract containing lotus/lotus in the present invention are not disclosed.
  • lotus especially the efficacy of lotus/lotus extract, and the efficacy and application of the compound extract containing lotus/lotus in the present invention are not disclosed.
  • CN105534815B discloses a skin care composition containing lotus active ingredients, but the specific efficacy of the lotus active ingredients is not disclosed.
  • the traditional Chinese medicine composition of the present invention comprises 15-35 parts by weight, preferably 20-30 parts by weight of lotus flower extract.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises Polygonum cuspidatum extract.
  • Polygonum cuspidatum is the rhizome and root of Liaoke Polygonum cuspidatum Sieb.Et Zucc. Also known as spot stick, bitter stick, acid stick, etc. Sexually bitter, slightly cold. Returns liver, gallbladder, lung meridian. Polygonum cuspidatum has the effect of promoting blood circulation and removing blood stasis, clearing away heat and detoxifying. Modern pharmacology shows that Polygonum cuspidatum contains resveratrol glycosides, which can effectively inhibit lipid peroxidation caused by free radical generating system, and also have antibacterial and antiviral effects.
  • CN111870572A discloses the antioxidant effect of Polygonum cuspidatum extract and its application.
  • the traditional Chinese medicine composition of the present invention comprises 15-30 parts by weight, preferably 15-25 parts by weight of Polygonum cuspidatum extract.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises Chuanxiong extract.
  • Chuanxiong the rhizome of Ligusticum chuanxiong Hort. also known as xiong fragrant fruit, husk Jingxiong et al. Sexual pungent, warm. Return liver, gallbladder, pericardium meridian.
  • Chuanxiong mainly has the functions of promoting blood circulation and removing blood stasis, promoting qi and relieving stagnation, dispelling wind and relieving pain.
  • the main ingredient is ligustrazine, which has the functions of anti-oxidation, anti-inflammatory, promoting blood microcirculation and improving immunity.
  • the traditional Chinese medicine composition of the present invention comprises 10-25 parts by weight, preferably 10-15 parts by weight of the Chuanxiong extract.
  • the anti-aging traditional Chinese medicine composition of the present invention comprises angelica extract.
  • Angelica sinensis the root of Angelica sinensis (Oliv.) Diels of Umbelliferae. Alias Gangui, Mawei Angelica, Yungui, etc. Sweet, acrid, bitter, warm in nature. Returns liver, heart and spleen meridians. Has the effect of invigorating blood and nourishing blood. Angelica mainly contains volatile oils, organic acids, etc., which can play an antioxidant and anti-inflammatory role.
  • the traditional Chinese medicine composition of the present invention comprises 10-25 parts by weight, preferably 10-15 parts by weight of Angelica sinensis extract.
  • This application is the first time to combine saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and angelica extract, and the various herbs in the obtained compound traditional Chinese medicine composition complement each other to achieve anti-aging , Improve the efficacy of the skin.
  • the traditional Chinese medicine composition of the present invention is suitable for the field of cosmetics.
  • the present inventors have unexpectedly found that the traditional Chinese medicine composition comprising saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and Angelica sinensis extract has anti-oxidative and/or anti-glycosylation effects. Therefore, the traditional Chinese medicine composition of the present invention can be used as a functional additive in cosmetics to assist in improving skin aging, oxidation, wrinkles and the like.
  • the weight ratio of saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and Angelica extract in the traditional Chinese medicine composition of the present invention is 0.1-0.5:1-3 :1-2:0.5-2:1-2:1-2.
  • the weight ratio of saffron extract, ginseng extract, lotus flower extract, polygonum extract, chuanxiong extract and angelica extract is 0.1:3:2:2:1:1.
  • the traditional Chinese medicine extract of the present invention is prepared by a solvent ultrasonic extraction method.
  • ethanol can be used as the extraction solvent.
  • 70% by volume ethanol can be used for extraction.
  • the extraction process can be performed in steps. For example, in the first step, 95 vol% ethanol is used for ultrasonic extraction, centrifugal filtration, and the filtrate is discarded; in the second step, 70 vol% ethanol is used for ultrasonic extraction, centrifugal filtration, and the filtrate is concentrated, and the desired extract is obtained after filtration.
  • the extraction step is carried out for a maximum of 24 hours, but can be shorter. For example, the extraction process can be performed for 30 minutes to 1 hour.
  • the present invention also relates to a skin external preparation, which comprises a traditional Chinese medicine composition of saffron extract, ginseng extract, lotus extract, polygonum extract, chuanxiong extract and angelica extract, as well as cosmetics, dermatology or pharmaceutically acceptable excipients.
  • the dosage of the traditional Chinese medicine composition of saffron extract, ginseng extract, lotus flower extract, Polygonum cuspidatum extract, Chuanxiong extract and Angelica extract 0.001-20% (w/w), preferably 0.008-10% (w/w), more preferably 0.01-5% (w/w), most preferably 0.01-2% (w/w).
  • the skin external preparation composition is a general concept of all ingredients generally used on the outside of the skin, and may be, for example, a cosmetic composition or a pharmaceutical composition.
  • the cosmetic composition can be basic cosmetic, facial cosmetic, body cosmetic, hair care cosmetic, etc. There is no special restriction on the dosage form thereof, and can be reasonably selected according to different purposes.
  • This external preparation for skin can be formulated into any suitable product form.
  • product forms include, but are not limited to, aerosol sprays, creams, lotions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions , hand pump sprays, sticks, masks and wipes.
  • topical preparations for skin can be conveniently used for the preparation or topical application as cosmetic, dermatological or pharmaceutical products by various methods well known in the art.
  • the skin external preparation composition of the present invention may include one or more of the following ingredients: antiallergic agent, antimicrobial agent, antioxidant, chelating agent, colorant depigmenting agent, emollient, emulsifier, epidermal exfoliating agent, Films, fragrances, humectants, insect repellents, lubricants, pharmaceutically active agents, moisturizing agents, lightfasteners, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickening agents agents, viscosity modifiers, vitamins, or any combination thereof.
  • Cosmetic, dermatologically or pharmaceutically acceptable excipients that can be used in the skin external preparation composition of the present invention are water phase, oil phase, gel, wax-in-water emulsion, oil-in-water emulsion, or water-in-oil in the form of an emulsion.
  • the aqueous phase is a mixture of one or more water-soluble or dispersible components, which may be liquid, semi-solid or solid at room temperature (25°C).
  • Excipients include or may be in the form of suspensions, dispersions or solutions in aqueous or hydro-alcoholic vehicles, which may contain thickening or gelling agents. Those skilled in the art can select the appropriate product form and the components contained therein based on the knowledge possessed by those skilled in the art.
  • the composition may include an aqueous phase, which may contain water or a mixture of water and at least one hydrophilic organic solvent, such as an alcohol, especially containing 2-5 carbon atoms linear or branched lower monohydric alcohols such as ethanol or propanol; polyols such as propylene glycol, sorbitol, glycerol, panthenol or polyethylene glycol and mixtures thereof.
  • an aqueous phase which may contain water or a mixture of water and at least one hydrophilic organic solvent, such as an alcohol, especially containing 2-5 carbon atoms linear or branched lower monohydric alcohols such as ethanol or propanol; polyols such as propylene glycol, sorbitol, glycerol, panthenol or polyethylene glycol and mixtures thereof.
  • the composition may also optionally contain a surfactant.
  • the composition may also comprise film-forming polymers such as polyurethane, polyacrylic homo- or copolymers, polyesters, hydrocarbon-based resins and/or silicone resins.
  • film-forming polymers such as polyurethane, polyacrylic homo- or copolymers, polyesters, hydrocarbon-based resins and/or silicone resins.
  • the polymer can be dissolved or dispersed in a cosmetically acceptable vehicle and optionally combined with a plasticizer.
  • compositions of the present invention may also comprise an oil phase containing oil-soluble or oil-dispersible components that are liquid at room temperature (25°C) and/or oily or waxy substances at room temperature, such as Waxes, semisolids, gums and mixtures thereof.
  • the oil phase may also contain organic solvents.
  • suitable oily substances include: hydrocarbon-based oils of animal origin, such as perhydrosqualene; hydrocarbon-based vegetable oils, such as liquid triglycerides of C4-10 fatty acids, such as heptanoic acid or caprylic triglycerides, or oils such as sunflower oil, corn oil, soybean oil, grapeseed oil, castor oil, avocado oil, caprylic/capric triglycerides, jojoba oil; Chain or branched hydrocarbons, such as liquid paraffin and its derivatives, petrolatum; synthetic esters and ethers, especially esters of fatty alcohols, such as isopropyl myristate, 2-ethylhexyl palmitate, hard 2-Octyldodecyl fatty acid, isostearyl isostearate; hydroxylated esters such as isostearyl lactate, octyl hydroxystearate, octyl hydroxystearate, hydroxystea
  • composition of the present invention may further contain any components commonly used in the cosmetic field. These components include preservatives, aqueous phase thickeners (extract biopolymers, synthetic polymers) and fatty phase thickeners, fragrances, hydrophilic and lipophilic actives, and mixtures thereof.
  • compositions of the present invention may also contain additional particulate phases, which may be pigments and/or pearlescent agents and/or fillers used in cosmetic compositions.
  • Pigments may be present in the composition, suitable inorganic pigments include titanium oxide, zirconium oxide and cerium oxide and zinc oxide, iron oxide and iron blue; suitable organic pigments include barium, strontium, calcium and aluminum lakes and carbon black.
  • Pearlescent agents may be present in the composition, suitable pearlescent agents include mica coated with titanium oxide, iron oxide or natural pigments.
  • Fillers may be present in the composition, suitable fillers include talc, silicon dioxide, zinc stearate, mica, kaolin, nylon powder, polyethylene powder, Teflon, starch, boron nitride, copolymers Microspheres, such as silicone resin microbeads.
  • the oily phase of the compositions of the present invention may comprise one or more waxes, gums or mixtures thereof.
  • Waxes include hydrocarbon-based waxes, fluorowaxes, and/or silicone waxes, and can be derived from vegetable, mineral, animal, and/or synthetic sources. Suitable waxes include beeswax, carnauba wax, candelilla wax, paraffin wax, microcrystalline wax, ozokerite; synthetic waxes include polyethylene waxes, silicone waxes containing C16-45.
  • the gums are typically polydimethylsiloxane or sodium carboxymethylcellulose or extracts, and the semi-solid materials are typically hydrocarbon-based compounds such as lanolin and its derivatives.
  • compositions of the present invention may be formulated into any suitable product form.
  • product forms include, but are not limited to, aerosol sprays, creams, lotions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions , hand pump sprays, sticks, masks and wipes.
  • the compositions of the present invention can be conveniently used in the preparation or topical application of products as cosmetic, dermatological or pharmaceutical products by various methods well known in the art.
  • the skin external preparation composition of the present invention may include one or more of the following ingredients: antiallergic agent, antimicrobial agent, antioxidant, chelating agent, colorant depigmenting agent, emollient, emulsifier, epidermal exfoliating agent, Films, fragrances, humectants, insect repellents, lubricants, pharmaceutically active agents, moisturizing agents, lightfasteners, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickening agents agents, viscosity modifiers, vitamins, or any combination thereof.
  • Embodiment 7 the preparation of traditional Chinese medicine composition
  • the mass ratio of the extract of Example 1 the extract of Example 2: the extract of Example 3: the extract of Example 4: the extract of Example 5: the extract of Example 6 (0.1:3:2:2:1:1 ) mixed to prepare a traditional Chinese medicine composition, and finally prepared into a 1% solid content solution for later use.
  • Embodiment 8 the preparation of Chinese medicine composition
  • the mass ratio of the extract of Example 1 the extract of Example 2: the extract of Example 3: the extract of Example 5: the extract of Example 6 (0.1:3:2:1:1) was mixed to prepare a traditional Chinese medicine composition, and finally It was prepared into a 1% solid solution for later use.
  • Embodiment 9 the preparation of Chinese medicine composition
  • the mass ratio of the extract of Example 1 the extract of Example 3: the extract of Example 5: the extract of Example 6 (0.1:2:1:1) was mixed to prepare a traditional Chinese medicine composition, and finally formulated into a 1% solid content solution, spare.
  • the mass ratio of the extract of Example 1 the extract of Example 2: the extract of Example 3: the extract of Example 4: the extract of Example 5: the extract of Example 6 (0.5:1:2:1:1:1 ) mixed to prepare a traditional Chinese medicine composition, and finally prepared into a 1% solid content solution for later use.
  • the mass ratio of the extract of Example 1 the extract of Example 2: the extract of Example 3: the extract of Example 4: the extract of Example 5: the extract of Example 6 (0.2:1:1:0.5:1:1 ) mixed to prepare a traditional Chinese medicine composition, and finally prepared into a 1% solid content solution for later use.
  • the mass ratio of the extract of Example 1 the extract of Example 2: the extract of Example 3: the extract of Example 4: the extract of Example 5: the extract of Example 6 (0.1:2:1:0.5:1:1 ) mixed to prepare a traditional Chinese medicine composition, and finally prepared into a 1% solid content solution for later use.
  • DPPH diphenylpicroyl free radical
  • ethanol solution is dark purple and has strong absorption near 517nm.
  • free radical scavengers the light absorption of DPPH is weakened due to its single electron pairing.
  • the fading degree of DPPH ethanol solution has a quantitative relationship with the number of electrons it accepts, which can evaluate the ability of antioxidants to scavenge free radicals or the magnitude of antioxidant activity. The greater the inhibition rate, the better the antioxidant effect.
  • Example 1-12 Take the prepared extract of Example 1-12 and prepare it with distilled water to make 2ml each of 12.5ug/ml, 62.5ug/ml and 312.5ug/ml, and carry out the test according to the following method. After 40min reaction at room temperature, absorbance is measured at 517nm value. Among them, DPPH was purchased from Sigma Company (sigma), and the active substance concentration was 60ug/ml.
  • T is the sample
  • T0 is the sample control
  • C is the blank
  • C0 is the blank control
  • Example 10 extract Two traditional Chinese medicines were removed from the extract of Example 9, and one traditional Chinese medicine was removed from the extract of Example 8, but the antioxidant effect of the extract of Example 9 was better than that of the extract of Example 8. It was speculated that the extract of Example 2 was The fresh ginseng extract has no significant antioxidant activity, and the proportion of the extract in Example 8 is relatively large. When the six drugs are compounded, they have a synergistic effect.
  • Tissue processing The skin tissue (from the leg of a 45-year-old male; purchased from Guangdong Boxi Biotechnology Co., Ltd.) was frozen in a liquid nitrogen tank, then taken out and thawed in hot water at 37°C, and then placed in a liquid nitrogen tank. Quick-freeze in liquid nitrogen, repeat 5 times. The skin was taken, placed in a 24-well plate, washed three times with PBS buffer containing double antibodies (purchased from Boster), and then the tissue was soaked in 75% ethanol for 5 minutes, and then washed three times with PBS buffer containing double antibodies , and finally placed in PBS buffer containing double antibody for 24h.
  • PBS buffer containing double antibodies purchased from Boster
  • UVA irradiated tissues In order to accelerate the saccharification reaction, 1 ml/well of PBS buffer was added to the 24-well plate. Except for the blank control group, other tissues in the incubation system were irradiated 7 days before the saccharification reaction, and the dose was 10J/well. cm 2 of UVA irradiation (UVA irradiator, the average intensity of UVA irradiator irradiation is 13.38mw/s, and the irradiation time of 10J/cm2 is 12min 27s), after the irradiation, the 24 wells were sealed with parafilm. The plate was sealed and placed in a 45°C oven for 72 h, and the reaction was repeated once after 72 h.
  • the blank control (BC) is PBS buffer solution containing double antibody
  • the negative control group (NC) is PBS buffer solution containing double antibody + 0.5mM methylglyoxal
  • the positive control group (PC) is PBS buffer containing double antibody Solution + 0.5mM methylglyoxal + 3mM aminoguanidine sulfate
  • experimental group (S) is PBS buffer solution + 0.5mM methylglyoxal + carnosine/Extract 7 containing double antibody.
  • the experimental group (S) was divided into S1 group and S2 group.
  • S1 is equivalent to an external source control product (currently generally recognized by consumers)
  • group S2 is the extract of the present invention.
  • the BC group was replaced with PBS buffer solution containing double antibodies;
  • the NC group was replaced with PBS buffer solution containing 0.5Mm methylglyoxal and double antibodies;
  • the PC group was replaced with 0.5Mm methylglyoxal and 3mM aminoguanidine PBS buffer solution of sulfate and double antibody;
  • group S was replaced with PBS buffer solution containing 0.5Mm methylglyoxal, 0.625% carnosine/Extract 7 and double antibody, each group set 3 parallels, when the sample was collected Tissues were fixed with 4% formaldehyde followed by immunohistochemistry.
  • the primary antibody kit in immunohistochemical detection was Anti-Carboxymethyl Lysine antibody [NF-1G], purchased from abcam.
  • the secondary antibody kit was VECTASTAIN ABC Kit (mouse IgG), purchased from Vector Laboratories.
  • Dewaxing of baked slices The paraffin slices were placed in a baking machine at 70°C, and baked for 4 hours.
  • Dewaxing and hydration Immerse the sections in xylene for 10 min, replace the xylene and repeat once, and then soak in absolute ethanol, 95% ethanol, and 75% ethanol for 5 min. Washed with PBS buffer 3 times, 5 min each time.
  • Antigen retrieval put the paraffin sections into 0.01M sodium citrate antigen retrieval solution, use high pressure to repair, take out after cooling, wash 3 times with PBS buffer, 5min each time.
  • Block peroxidase add 1 drop of 3% hydrogen peroxide to each section, incubate at room temperature for 30 min to block the activity of endogenous peroxidase, wash with PBS buffer three times, 5 min each time.
  • Serum blocking dropwise add serum homologous to the secondary antibody for blocking at 37°C for 1 h.
  • Primary antibody incubation add primary antibody working solution dropwise, incubate at 4°C overnight, and wash with PBS buffer three times for 5 min each time.
  • Secondary antibody incubation Add the secondary antibody working solution dropwise, incubate at 4°C for 1 h, and wash with PBS buffer for 3 times, 5 min each time.
  • ABC complex incubation dropwise add ABC complex solution, incubate at room temperature for 30 min, and wash with PBS buffer three times, 5 min each time.
  • DAB staining add 1 drop of freshly prepared DAB solution to each section and observe under microscope for 5-30s.
  • Dehydration Dehydrate the slices with 75% ethanol, 95% ethanol, absolute ethanol, and anhydrous ethanol in sequence for 5 minutes, then soak the slices in xylene for 10 minutes, replace the xylene, repeat once, dry, mount with neutral resin, and dry. dry, watch.
  • the relative expression of AGEs in the isolated skin the expression of AGEs in the isolated skin/the average expression of AGEs in the isolated skin of the control group
  • S1 is 0.625% carnosine
  • S2 is 0.625% Example 7 extract.
  • the extracts of Example 7 and Examples 9-12 were used in the preparation of external preparations for skin.
  • the external preparation for skin is preferably a cosmetic composition, such as lotion, essence, cream and the like.
  • the weight percentage of the composite extract in the external preparation for skin is 0.0001%-20% (w/w).
  • the preferred weight percent is 0.001% to 10% (w/w).
  • a more preferred weight percentage is 0.001%-5% (w/w).
  • the most preferred weight percent is 0.01%-5% (w/w).

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Abstract

公开了一种抗衰老中药组合物及其外用剂和制备方法以及在非治疗性目的的抗皮肤衰老中的用途和在制备抗皮肤衰老的化妆品中的用途。该组合物包含：西红花提取物1-10重量份，人参提取物15-40重量份，荷花提取物15-35重量份，虎杖提取物15-30重量份，川芎提取物10-25重量份，当归提取物10-25重量份，其中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物采用溶剂超声提取法制备。

Description

[根据细则37.2由ISA制定的发明名称]　抗衰老中药组合物及其制备方法和非治疗目的用途以及制备化妆品的用途 技术领域
本发明涉及天然药物化学领域和化妆品领域，具体涉及一种具有抗衰老功效的中药组合物，该中药组合物的制备方法以及应用。
背景技术
化妆品工业中抗衰老的化妆品一直被人们所关注，因为针对抵御皮肤老化的问题是大家所关注的重点，保护皮肤、延缓皮肤衰老是很多人的梦想。皮肤衰老是一种持续渐进性的生理过程，直接影响皮肤的外观和功能。
非酶糖基化NEG是一系列复杂的非酶促反应，还原糖直接与蛋白质残基结合，产生席夫碱(Schiff)，裂解为葡糖胺重排(Amadori)产物，随后经过脱水、环化、氧化和重排进一步降解为一系列活性醛酮化合物(活性羰基化合物RCS)。RCS具有比还原糖更高的活性，可快速与蛋白质游离的氨基结合，最终生成不可逆的棕黄色的具有荧光性质的物质，这些物质统称为晚期糖基化终末产物(Advanced Glycation End products，AGEs)。
人皮肤组织中有大量的胶原蛋白与弹性蛋白。这两种蛋白代谢缓慢，而且含较多的赖氨酸和羟赖氨酸，这为发生NEG反应提供了物质基础。皮肤蛋白质与还原糖发生NEG形成AGEs，随着年龄的增长而增多。随着AGEs进行性增加，胶原蛋白形成分子间交联，不但降低***的通透性，还使养料及废物的扩散性能减弱、组织延展性和硬度增加；降低了胶原的可溶性而难以被胶原酶水解，造成皮肤弹性下降，皱纹产生，而且随着年龄增长而加深。
氧化是AGEs形成过程中至关重要的步骤。AEGs形成的中间产物一活性羰基(二羰基(dicarbonyl)，如丙二醛MDA、3-脱氧葡萄糖酮醛3-deoxyglucosome)都由Amadori产物氧化降解或自氧化而来。AGEs可直接降低体内抗氧化酶的活性。提高皮肤氧化应激水平。总体来说，氧化应激 可以促进NEG过程，AGEs可提高氧化应激水平。事实上，许多抗氧化剂被证实具有抗糖化活性，如：抗坏血酸、生育酚、***钠、核黄素、锌、锰等在体外实验中都发现具有抗糖化作用。绿茶、维生素C(VC)、维生素E(VE)和乙酰半胱氨酸、芦丁的混合物可以抑制小鼠皮肤胶原蛋白非酶糖化。
目前人们已知的AGEs结构形式有：羧甲基赖氨酸(CML)、羧乙基赖氧酸(CEL)、戊糖苷素、糖基化胶原、吡咯素以及二赖氨酰咪唑啉衍生物等。大部分具有荧光特殊性(如戊糖苷素、糖基化肢原)，也有的不具有荧光特性(如CML、CEL)。因此对于抗糖化功效评价目前最典型的是采用生化反应方法，即采用牛血清白蛋白-葡萄糖(BSA-glucose)和牛血清白蛋白-丙酮醛(BSA-MGO)等模型，通过荧光分光光度法评价反应后AGEs的含量，另外基于离体皮，通过免疫组化的方法进行AGEs的主要结构类型羧甲基赖氨酸的检测，从而评估抗糖化功效。
因此，已提出了多种途径和物质来正面影响弹性蛋白及与其相关的皮肤特性。但是，本发明意外地发现，包含西红花、人参、荷花、虎杖、川芎和当归提取物的中药组合物，具有优异的抗氧化和良好的抗糖基化的作用。
发明内容
一方面，本发明提供了一种抗衰老的中药组合物，其包含：
西红花提取物1-10重量份，
人参提取物15-40重量份，
荷花提取物15-35重量份，
虎杖提取物15-30重量份，
川芎提取物10-25重量份，
当归提取物10-25重量份，
其中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物采用溶剂超声提取法制备。
在优选的实施方式中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的重量比为0.1-0.5:1-3:1-2:0.5-2:1-2:1-2。在更优选的实施方式中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的重量比为0.1:3:2:2:1:1。
在优选的实施方式或者，本发明的提取物采用乙醇，优选70体积％的乙醇进行提取。
另一方面，本发明还涉及包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的中药组合物在非治疗目的的抗皮肤衰老方面的应用。在优选的实施方式中，所述抗皮肤衰老通过抗氧化和/或抗糖基化实现。
另一方面，本发明还涉及包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的中药组合物在制备用于抗皮肤衰老的化妆品中的应用。在优选的实施方式中，所述抗皮肤衰老通过抗氧化和/或抗糖基化实现。
又一方面，本发明还涉及包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的中药组合物的制备方法，所述方法包括：
采用溶剂超声提取法分别制备西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物；
将西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物按照重量份数进行组合。
又一方面，本发明提供了一种皮肤外用剂，所述皮肤外用剂包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的中药组合物。在优选的实施方式中，所述皮肤外用剂包含0.01-5重量％的中药组合物。
附图说明
下面结合附图进一步说明本发明。
图1是晚期糖基化终末产物(AGEs)相对表达含量的结果。其中，BC代 表空白对照，NC代表阴性对照，PC代表阳性对照。
图2是免疫组化检测结果。采用的显微镜是OLMPUS BX53，放大倍数分别是20倍物镜×10倍目镜以及40倍物镜×10倍目镜。其中，表达量分析的图片为40倍物镜×10倍目镜的图片。
发明详述
除非另有定义，否则本文使用的所有科学技术术语的含义与本发明所属领域的普通技术人员通常所理解的含义相同。另外，将本文提及的所有出版物、专利申请、专利及其他参考文献以引用方式并入本文中。除非另有指明，否则百分比是指重量百分比。
本文所用的“抗衰老”包括减轻、降低、预防、改善或消除诸如细纹和皱纹、弹性损失、皮肤不平、红疤和老年斑的存在。
本文所用的“皱纹”包括微细纹、微皱纹或粗皱纹。皱纹的实例包括但不限于眼睛周围的微细纹(例如“鱼尾纹”)、前额和颊皱纹、眉心纹和嘴巴周围的笑纹。
本文所用的“弹性损失”包括皮肤或组织的弹性或结构完整性的损失，包括但不限于松垂、松弛和松散组织。弹性或组织结构完整性的损失可由多种因素所致，包括但不限于疾病、衰老、激素变化、机械创伤、环境损害，或者是向组织施用诸如美容品或药物的产品的结果。
本文所用的“皮肤不平”是指与弥漫性或斑驳性色素沉着有关的皮肤状况，所述色素沉着可分类为色素沉着过度，如发炎后色素沉着过度。
本文所用的“红疤”是指与发红或红斑有关的皮肤状况。
本文所用的“老年斑”是指与不连续色素沉着有关的皮肤状况，例如可在脸上以及手上发展的较深色素沉着小区域。
本文所用的“化妆品”指能保持、恢复、赋予、刺激或增强体美外观或者似乎能增进美貌或年轻的美容物质或制品，具体地涉及到组织或皮肤的外观。
本文所用的“化妆品上有效量”是指足以治疗一种或多种皮肤老化迹象、但充分低以避免严重副作用的生理活性化合物或组合物的量。化合物或组 合物的美容上有效量要随以下因素而变：所治疗的具体病症、最终用户的年龄和身体状况、所治疗/预防的病症的严重程度、治疗的持续时间、其他治疗的性质、所采用的具体化合物或产品/组合物、所具体采用的美容上可接受的载体等等。
西红花提取物
本发明抗衰老中药组合物包含西红花提取物。
西红花，为鸢尾科番红花Crocus sativus L.的柱头。别名有藏红花、番红花等。性甘，平。归心、肝经。有活血祛瘀，散郁开结的作用。现代研究表明西红花具有抗氧化、抗凝血及免疫调节等功效。
现有技术中虽有披露西红花提取物的应用，但并没有披露西红花提取物的功效，更没有披露本发明中含有西红花的复方提取物的功效和应用。例如，CN110812299A公开了一直含有西红花的爽肤水及其配制工艺。又如，CN106821932A公开了含有西红花提取液的化妆品，其中并未披露西红花提取液的功效。再如，CN110279640A公开了西红花提取物具有美白功效。
在优选的实施方式中，本发明的中药组合物包含1-10重量份，优选1-2重量份的西红花提取物。
人参提取物
本发明抗衰老中药组合物包含人参提取物。
人参，为五加科人参Panax ginseng C.A.Mey.的根。别称有黄参、玉精、血参、孩儿参等。性甘，微温。归肺、脾、心、肾经。具有大补元气，生津安神的效果。文献报道人参及其制剂主要成分为人参皂苷，在提高学习能力、易化记忆方面有显著的促进作用，同时还能够抑制金黄色葡萄球菌、提升自身免疫能力。不仅如此，人参还具有抗氧化、抗衰老、抗炎之效。
现有技术中虽有披露人参根、人参花籽等提取物的应用，但并没有披露人参，尤其是鲜人参提取物的功效，更没有披露本发明中含有鲜人参的复方提取物的功效和应用。例如，CN110787075A一种含有人参根提取物和 人参籽油的护肤油组合物，其中未公开人参根或人参籽油的功效。
在优选的实施方式中，本发明的中药组合物包含15-40重量份，优选15-35重量份的人参提取物。
荷花提取物
本发明抗衰老中药组合物包含荷花提取物。
荷花，为睡莲科莲Nelumbo nucifera Gaertn.的花蕾。又名菡萏、芙蕖、芙蓉。性苦、甘，平。归肝、胃经。荷花能散瘀止血，祛湿消风。荷花中含有丰富的黄酮成分，是良好的抗氧化剂和抑菌剂，荷花黄酮类成分能够清楚超氧阴离子自由基及羟基自由基。
现有技术中虽有披露荷花活性物的应用，但并没有披露莲花，尤其是莲花/荷花提取物的功效，更没有披露本发明中含有莲花/荷花的复方提取物的功效和应用。例如，CN105534815B公开了一种含有荷花活性成分的护肤组合物，其中并未公开荷花活性成分的具体功效。
在优选的实施方式中，本发明的中药组合物包含15-35重量份，优选20-30重量份的荷花提取物。
虎杖提取物
本发明抗衰老中药组合物包含虎杖提取物。
虎杖，为廖科虎杖Polygonum cuspidatum Sieb.Et Zucc.的根茎及根。又被称为斑杖、苦杖、酸杖等。性苦，微寒。归肝、胆、肺经。虎杖有活血祛瘀，清热解毒的功效。现代药理表明虎杖中含有白藜芦醇苷，能够有效地抑制由自由基发生***引起的脂质过氧化，还具有抗菌抗病毒作用。
现有技术中虽有披露虎杖提取物及应用，但并没有披露本发明中含有虎杖的复方提取物的功效和应用。例如，CN111870572A公开了虎杖提取物的抗氧化作用及其应用。
在优选的实施方式中，本发明的中药组合物包含15-30重量份，优选15-25重量份的虎杖提取物。
川芎提取物
本发明抗衰老中药组合物包含川芎提取物。
川芎，为伞形科川芎Ligusticum chuanxiong Hort.的根茎。别称有芎
Figure PCTCN2021127252-appb-000001
香果、胡
Figure PCTCN2021127252-appb-000002
京芎等。性辛，温。归肝、胆、心包经。川芎主要有活血祛瘀、行气开郁、祛风止痛的作用。主要成分为川芎嗪，具有抗氧化、抗炎、促进血液微循环、提升免疫力的功效。
同样，现有技术中被披露本发明中含有川芎的复方提取物的功效和应用。
在优选的实施方式中，本发明的中药组合物包含10-25重量份，优选10-15重量份的川芎提取物。
当归提取物
本发明抗衰老中药组合物包含当归提取物。
当归，为伞形科当归Angelica sinensis(Oliv.)Diels的根。别名干归、马尾当归、云归等。性甘、辛、苦，温。归肝、心、脾经。具有活血补血之效。当归主要含挥发油、有机酸等，能够起到抗氧化、抗炎的作用。
现有技术如CN102209526B虽有披露含有极细当归提取物的组合物，但并没有披露当归提取物，更没有披露本发明中含有当归的复方提取物的功效和应用。
在优选的实施方式中，本发明的中药组合物包含10-25重量份，优选10-15重量份的当归提取物。
中药组合物
本申请首次将西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物进行组合，得到的复方中药组合物中各味药之间相辅相成，以达到抵抗衰老、改善皮肤之功效。
本发明的中药组合物适用于化妆品领域。本发明意外地发现，包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物的中药组合物具有抗氧化和/或抗糖基化作用。因此，本发明的中药 组合物可以作为功效添加剂加入到化妆品中使用，以辅助改善皮肤衰老、氧化、皱纹问题等。
在本发明一个实施方式中，本发明的中药组合物中西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物的重量比为0.1-0.5:1-3:1-2:0.5-2:1-2:1-2。在优选的实施方式中，西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物的重量比为0.1:3:2:2:1:1。
提取方法
本发明的中药提取物通过溶剂超声提取法制备。例如，可以采用乙醇作为提取溶剂。在优选的实施方式中，可以采用70体积％的乙醇进行提取。
在一个具体的实施方式中，提取过程可以分步进行。例如，第一步采用95体积％的乙醇进行超声提取，离心过滤，弃去滤液；第二步采用70体积％的乙醇进行超声提取，离心过滤，滤液浓缩，过滤后获得所需的提取物。进行提取步骤的时间最多为24小时，但还可更短。例如，提取过程可以进行30分钟至1小时。
皮肤外用剂
本发明还涉及一种皮肤外用剂，该皮肤外用剂包含西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物的中药组合物以及化妆品、皮肤病学或药学上可接受的赋形剂。
在一些优选的实施方式中，以所述皮肤外用剂的总重量计，西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物的中药组合物的用量为0.001-20％(w/w)，优选为0.008-10％(w/w)，更优选为0.01-5％(w/w)，最优选为0.01-2％(w/w)。
所述皮肤外用剂组合物是通常用于皮肤外部的所有成分的统称概念，例如可以是化妆料组合物或药学组合物。所述化妆料组合物中可以是基础化妆料、面部妆容化妆料、身体用化妆料、头发护理用化妆料等，对其剂型无特殊限制，根据不同目的可合理选择。
这种皮肤外用剂可以配制成任何合适的产品形式。这类产品形式包括，但 不限于气溶胶型喷雾剂、霜剂、乳液、固体、液体、分散体、泡沫、凝胶、化妆水、摩丝、软膏、粉剂、贴剂、润发油、溶液、手按泵型喷雾剂、棒状物、面膜和湿纸巾。可以这种皮肤外用剂通过本领域众所周知的各种方法便利地用于制备或作为化妆品、皮肤病学或药物局部施用产品。
本发明的皮肤外用剂组合物可以包括一种或多种下列成分：抗过敏剂、抗微生物剂、抗氧化剂、螯合剂、着色剂去色素剂、润肤剂、乳化剂、表皮脱落剂、成膜剂、香料、保湿剂、昆虫驱避剂、润滑剂、药物活性剂、增湿剂、耐光剂、防腐剂、护肤剂、皮肤渗透增强剂、防晒剂、稳定剂、表面活性剂、增稠剂、粘度调节剂、维生素或其任意组合。
可以用于本发明皮肤外用剂组合物的化妆品、皮肤病学或药学上可接受的赋形剂为水相、油相、凝胶、水包蜡型乳液、水包油型乳液或油包水型乳液的形式。水相为一种或多种水溶性或分散性组分的混合物，其在室温(25℃)下可以为液体、半固体或固体。赋形剂包括或可以为在水或水-醇赋形剂中的混悬液、分散液或溶液的形式，其可以含有增稠剂或凝胶剂。本领域技术人员可以基于本领域技术人员掌握的知识选择合适的产品形式，其中包含的组分。
所述的组合物可以包括水相，该水相可以含有水或水与至少一种亲水性有机溶剂的混合物，所述的亲水性有机溶剂诸如醇，尤其是含有2-5个碳原子的直链或支链低级一元醇，如乙醇或丙醇；多元醇，如丙二醇、山梨醇、甘油、泛醇或聚乙二醇及其混合物。
当发明的组合物为乳液形式时，该组合物还可以任选包含表面活性剂。
所述的组合物还可以包含成膜聚合物，如聚氨基甲酸酯、聚丙烯酸均聚物或共聚物、聚酯、基于烃的树脂和/或硅氧烷树脂。可以将聚合物溶于或分散于化妆品可接受的赋形剂中并且任选与增塑剂合并。
本发明的组合物还可以包含油相，所述的油相含有在室温(25℃)下为液体的油溶性或油分散性组分和/或在室温下为油状或蜡状的物质，如蜡、半固体、树胶及其混合物。该油相还可以含有有机溶剂。
通常在室温下为液体，合适的油性物质包括：来源于动物的基于烃的油，如全氢化角鲨烯；基于烃的植物油，如液体的C4-10脂肪酸的甘油三 酯类，例如庚酸或辛酸甘油三酯类，或油，例如向日葵油、玉米油、大豆油、葡萄籽油、蓖麻油、鳄梨油、辛酸/癸酸甘油三酯类、霍霍巴油；矿物或合成来源的直链或支链烃类，例如液体石蜡及其衍生物、凡士林；合成酯类和醚类，特别是脂肪醇的酯类，例如肉豆蔻酸异丙酯、棕榈酸2-乙基己酯、硬脂酸2-辛基十二烷基酯、异硬脂酸异硬脂醇酯；羟基化酯类，例如乳酸异硬脂醇酯、羟基硬脂酸辛酯、羟基硬脂酸辛酯、羟基硬脂酸辛基十二烷基酯、脂肪醇的庚酸酯类、辛酸酯类和癸酸脂类；多元醇酯类，例如丙二醇二辛酸酯、新戊二醇二庚酸酯、二甘醇二异壬酸酯和季戊四醇酯类；含有C12-26的脂肪醇类，例如辛基十二烷醇、2-丁基辛醇、2-己基癸醇、2-十一烷基十五烷醇、油醇；基于部分烃的氟油和/或氟硅油，硅油，在室温下为液体或半固体的挥发性或非挥发性的直链或环状聚甲基硅氧烷，例如环状聚二甲基硅氧烷和聚二甲基硅氧烷，其任选包含苯基，例如苯基三甲基硅氧烷、硅氧烷及其混合物。
本发明的组合物可以进一步包含常用于化妆品领域中的任何组分。这些组分包括防腐剂、水相增稠剂(提取物生物聚合物、合成聚合物)和脂肪相增稠剂、芳香剂、亲水性和亲脂性活性剂及其混合物。
本发明的组合物还可以包含另外的颗粒相，所述的颗粒相可以为化妆品组合物中使用的颜料和/或珠光剂和/或填充剂。
颜料可以存在于组合物中，合适的无机颜料包括氧化钛、氧化锆和氧化铈以及氧化锌、氧化铁和铁蓝；合适的有机颜料包括钡、锶、钙和铝色淀和碳黑。
珠光剂可以存在于组合物中，合适的珠光剂包括涂覆了氧化钛、氧化铁或天然颜料的云母。
填充剂可以存在于组合物中，合适的填充剂包括滑石粉、二氧化硅、硬脂酸锌、云母、高岭土、尼龙粉末、聚乙烯粉末、特氟龙、淀粉、一氮化硼、共聚物微球，例如硅氧烷树脂微珠。
本发明组合物的油相可以包含一种或多种蜡、树胶或其混合物。蜡包括基于烃的蜡、氟蜡和/或硅氧烷蜡，并且可以来源于植物、矿物、动物和/或合成来源。合适的蜡包括蜂蜡、巴西棕榈蜡、小烛树蜡、石蜡、微晶蜡、 地蜡；合成蜡包括聚乙烯蜡、含有C16-45的硅氧烷蜡。树胶一般为聚二甲基硅氧烷或羧甲基纤维素钠或提取物类，并且半固体物质一般为基于烃的化合物，如羊毛脂及其衍生物。
可以将本发明的组合物配制成任何合适的产品形式。这类产品形式包括，但不限于气溶胶型喷雾剂、霜剂、乳液、固体、液体、分散体、泡沫、凝胶、化妆水、摩丝、软膏、粉剂、贴剂、润发油、溶液、手按泵型喷雾剂、棒状物、面膜和湿纸巾。可以将本发明的组合物通过本领域众所周知的各种方法便利地用于制备或作为化妆品、皮肤病学或药物局部施用产品。
本发明的皮肤外用剂组合物可以包括一种或多种下列成分：抗过敏剂、抗微生物剂、抗氧化剂、螯合剂、着色剂去色素剂、润肤剂、乳化剂、表皮脱落剂、成膜剂、香料、保湿剂、昆虫驱避剂、润滑剂、药物活性剂、增湿剂、耐光剂、防腐剂、护肤剂、皮肤渗透增强剂、防晒剂、稳定剂、表面活性剂、增稠剂、粘度调节剂、维生素或其任意组合。
具体实施方式
下面结合具体的实施例进一步阐述本发明。但是，应该明白，这些实施例仅用于说明本发明而不构成对本发明范围的限制。下列实施例中未注明具体条件的试验方法，通常按照常规条件，或按照制造厂商所建议的条件。除非另有说明，所有的百分比和份数按重量计。
以下实施例中采用的药材来源和产地如下：
西红花 京皖饮片厂，产地西藏；
鲜人参 京皖饮片厂，产地吉林；
荷花 京皖饮片厂，产地湖南；
虎杖 京皖饮片厂，产地湖北；
川芎 京皖饮片厂，产地四川；
当归 京皖饮片厂，产地甘肃。
实施例1：西红花提取物制备
称取西红花10g，用10倍95％乙醇超声提取30min，离心过滤，弃去 滤液。药渣用20倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含20.02％，最终配制成固含1％溶液，备用。
实施例2：鲜人参提取物制备
称取鲜人参100g，打粗粉，用10倍95％乙醇超声提取30min，离心过滤，弃去滤液。药渣用8倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含2.43％，最终配制成固含1％溶液，备用。
实施例3：荷花提取物制备
称取荷花100g，用10倍95％乙醇超声提取30min，离心过滤，弃去滤液。药渣用20倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含4.91％，最终配制成固含1％溶液，备用。
实施例4：虎杖提取物制备
称取虎杖100g，用10倍95％乙醇超声提取30min，离心过滤，弃去滤液。药渣用20倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含6.77％，最终配制成固含1％溶液，备用。
实施例5：川芎提取物制备
称取川芎100g，用10倍95％乙醇超声提取30min，离心过滤，弃去滤液。药渣用20倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含5.72％，最终配制成固含1％溶液，备用。
实施例6：当归提取物制备
称取当归100g，用10倍95％乙醇超声提取30min，离心过滤，弃去滤液。药渣用20倍70％乙醇超声40min，离心过滤，滤液于55℃条件下浓缩，4℃静置过夜。取出后，在3℃、3500rpm条件下离心15min，滤纸过滤，最终配制成1g/ml的溶液，固含33.35％，最终配制成固含1％溶液，备用。
实施例7：中药组合物的制备
按质量比实施例1提取物：实施例2提取物：实施例3提取物：实施例4提取物：实施例5提取物：实施例6提取物(0.1:3:2:2:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例8：中药组合物的制备
按质量比实施例1提取物：实施例2提取物：实施例3提取物：实施例5提取物：实施例6提取物(0.1:3:2:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例9：中药组合物的制备
按质量比实施例1提取物：实施例3提取物：实施例5提取物：实施例6提取物(0.1:2:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例10：中药组合物的制备
按质量比实施例1提取物：实施例2提取物：实施例3提取物：实施例4提取物：实施例5提取物：实施例6提取物(0.5:1:2:1:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例11：中药组合物的制备
按质量比实施例1提取物：实施例2提取物：实施例3提取物：实施 例4提取物：实施例5提取物：实施例6提取物(0.2:1:1:0.5:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例12：中药组合物的制备
按质量比实施例1提取物：实施例2提取物：实施例3提取物：实施例4提取物：实施例5提取物：实施例6提取物(0.1:2:1:0.5:1:1)混合制备中药组合物，最终配制成固含1％溶液，备用。
实施例13：中药提取物的抗氧化性能评价
DPPH(二苯代苦味酰基自由基)是一种稳定的长寿命自由基，其乙醇溶液呈深紫色，在517nm附近有强吸收。当有自由基清除剂存在时，由于与其单电子配对而使DPPH光吸收减弱。DPPH乙醇溶液褪色程度与其接受的电子数呈定量关系，借此可评价抗氧化剂清除自由基的能力或抗氧化活性的大小，抑制率越大表示抗氧化效果越好。
取制备好的实施例1-12提取物，以蒸馏水配制成12.5ug/ml、62.5ug/ml、312.5ug/ml各2ml，按下表方法进行试验，室温反应40min后，于517nm处测吸光值。其中，DPPH购自西格玛公司(sigma)，活性物浓度60ug/ml。
结果如下所示。
表1
单位/ml T T0 C C0
样品 2 2 － －
水 － － 2 2
DPPH 2 － 2 －
无水乙醇 － 2 － 2
Figure PCTCN2021127252-appb-000003
其中T为样品，T0为样品对照，C为空白，C0为空白对照。
表2
Figure PCTCN2021127252-appb-000004
由DPPH清除自由基结果可知，实施例7-12提取物的抗氧化能力优于实施例1-6提取物，其中实施例7提取物的抗氧化能力最强，认为复合提取物比例最佳，其次为实施例10提取物。实施例9提取物中去除2味中药，实施例8提取物中去除了1味中药，但实施例9提取物的抗氧化作用优于实施例8提取物，推测是由于实施例2提取物即鲜人参提取物并无显著抗氧化活性，同时在实施例8提取物中比例较大所致。当6味药物进行复配时，具有协同作用。
实施例14：中药组合物的抗糖化性能评价
1.实验方法：
(1)组织处理：将皮肤组织(来源于45岁男性腿部；购自广东博溪生物科技有限公司)冻存于液氮罐中，后取出置于37℃热水中融化，再置于液氮中速冻，如此反复5次。取皮，置于24孔板，用含有双抗PBS缓冲液(购自博士德公司)冲洗3次，再将组织放入75％乙醇中浸泡5min，再用含双抗PBS缓冲液冲洗3次，最后置于含双抗PBS缓冲液中24h。
(2)UVA辐照组织：为加速糖化反应，于24孔板添加1ml/孔糖化反应PBS缓冲液，除空白对照组，其他孵育体系组织均在糖化反应前7天接受辐照计量为10J/cm 2的UVA辐照(UVA辐照仪，UVA辐照仪的辐照平均强度为13.38mw/s，10J/cm2的辐照时间为12min 27s)，辐照结束后，用封口膜将24孔板密封，置于45℃烘箱中反应72h，72h后重复1次。
(3)按下表方式进行操作。
表3
Figure PCTCN2021127252-appb-000005
Figure PCTCN2021127252-appb-000006
其中空白对照在(BC)为含有双抗的PBS缓冲溶液，阴性对照组(NC)为含有双抗PBS缓冲溶液+0.5mM甲基乙二醛，阳性对照组(PC)为含有双抗PBS缓冲溶液+0.5mM甲基乙二醛+3mM氨基胍硫酸盐，实验组(S)为含有双抗PBS缓冲溶液+0.5mM甲基乙二醛+肌肽/实施例7提取物。实验组(S)分为S1组和S2组。S1相当于外部来源对照产品(目前消费者普遍认可的功效物)，S2组是本发明的提取物。
换液时BC组换成含双抗PBS缓冲溶液；NC组换成含0.5Mm甲基乙二醛和双抗的PBS缓冲溶液；PC组换成含0.5Mm甲基乙二醛、3mM氨基胍硫酸盐和双抗的PBS缓冲溶液；S组换成含0.5Mm甲基乙二醛、0.625％肌肽/实施例7提取物和双抗的PBS缓冲溶液，每组设置3个平行，收样时将组织用4％甲醛进行固定，然后免疫组化。
(4)免疫组化检测
免疫组化检测中一抗试剂盒是Anti-Carboxymethyl Lysine antibody[NF-1G]，购自abcam。二抗试剂盒是VECTASTAIN ABC Kit(小鼠IgG)， 购自维克多实验室公司(Vector Laboratories)。
烤片脱蜡：石蜡切片置于70℃烤片机中，烤片4小时。
脱蜡水化：将切片置于二甲苯中浸泡10min，更换二甲苯重复1次，然后依次在无水乙醇、95％乙醇、75％乙醇中浸泡5min。PBS缓冲液清洗3次，每次5min。
抗原修复：将石蜡切片放入0.01M柠檬酸钠抗原修复溶液，采用高压修复，冷却后取出，PBS缓冲液清洗3次，每次5min。
阻断过氧化物酶：每张切片加1滴3％过氧化氢，室温下孵育30min，以阻断内源性过氧化物酶的活性，PBS缓冲液清洗3次，每次5min。
血清封闭：滴加与二抗同源的血清37℃封闭1h。
一抗孵育：滴加一抗工作液，4℃孵育过夜，PBS缓冲液清洗3次，每次5min。
二抗孵育：滴加二抗工作液，4℃孵育1h，PBS缓冲液清洗3次，每次5min。
ABC复合物孵育：滴加ABC复合液，室温孵育30min，PBS缓冲液清洗3次，每次5min。
DAB染色：每张切片加1滴新鲜配置的DAB液，显微镜观察5-30s。
复染：苏木素复染30s。
脱水：切片依次用75％乙醇、95％乙醇、无水乙醇、无水乙醇脱水5min，再将切片置于二甲苯中浸泡10min，更换二甲苯重复1次，干燥，中性树脂封固，晒干，观察。
2.实验结果：
表4
Figure PCTCN2021127252-appb-000007
Figure PCTCN2021127252-appb-000008
离体皮AGEs相对表达量＝离体皮AGEs表达量/对照组离体皮AGEs平均表达量
其中S1为0.625％肌肽，S2为0.625％实施例7提取物。
由免疫组化检测结果可知，NC组AGEs含量相较BC组均显著上升，成功建立基于离体皮的糖化皮肤模型。与NC组相比较，S组的AGEs含量同PC组的氨基胍硫酸盐一致，均显著下降，说明肌肽和实施例7提取物均有一定的抗糖化功效，统计学差异分析，两者之间无差异(p>0.5)，说明肌肽和实施例7提取物的抗糖功效无差异。
实施例7和实施例9-12的提取物用于皮肤外用剂的制备。所述皮肤外用剂优选为化妆品组合物，例如化妆水、精华液、乳霜等。所述复合提取物在皮肤外用剂中的重量百分比为0.0001％-20％(w/w)。优选的重量百分比为0.001％-10％(w/w)。更优选的重量百分比为0.001％-5％(w/w)。最优选的重量百分比为0.01％-5％(w/w)。
以下是中药组合物在皮肤外用剂中的具体应用的实施例，及其这些剂型的配方和制备方法。以下各表中“-”表示无添加。
实施例15：面霜的制备
Figure PCTCN2021127252-appb-000009
Figure PCTCN2021127252-appb-000010
实施例16：乳液的制备
Figure PCTCN2021127252-appb-000011
Figure PCTCN2021127252-appb-000012
实施例17：啫喱的制备
Figure PCTCN2021127252-appb-000013
实施例18：化妆水的制备
Figure PCTCN2021127252-appb-000014
Figure PCTCN2021127252-appb-000015
实施例19：精华液的制备
Figure PCTCN2021127252-appb-000016
实施例20：面膜的制备
Figure PCTCN2021127252-appb-000017
Figure PCTCN2021127252-appb-000018
实施例21：眼霜的制备
Figure PCTCN2021127252-appb-000019
实施例22：气雾(清洁泡)的制备
Figure PCTCN2021127252-appb-000020
实施例23：喷雾的制备
Figure PCTCN2021127252-appb-000021
实施例24：沐浴露的制备
Figure PCTCN2021127252-appb-000022
Figure PCTCN2021127252-appb-000023
实施例25：洗面奶的制备
Figure PCTCN2021127252-appb-000024
Figure PCTCN2021127252-appb-000025

Claims (11)

  1. 一种抗衰老的中药组合物，其包含：
    西红花提取物1-10重量份，
    人参提取物15-40重量份，
    荷花提取物15-35重量份，
    虎杖提取物15-30重量份，
    川芎提取物10-25重量份，
    当归提取物10-25重量份，
    其中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物采用溶剂超声提取法制备。
  2. 如权利要求1所述的中药组合物，其中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的重量比为0.1-0.5:1-3:1-2:0.5-2:1-2:1-2。
  3. 如权利要求2所述的中药组合物，其中，所述西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物、当归提取物的重量比为0.1:3:2:2:1:1。
  4. 如权利要求1-3中任一项所述的中药组合物，其中，所述提取物采用乙醇，优选70体积％的乙醇进行提取。
  5. 如权利要求1-3中任一项所述的中药组合物在非治疗目的的抗皮肤衰老方面的应用。
  6. 如权利要求5所述的应用，其中，所述抗皮肤衰老通过抗氧化和/或抗糖基化实现。
  7. 如权利要求1-3中任一项所述的中药组合物在制备用于抗皮肤衰老的化妆品中的应用。
  8. 如权利要求7所述的应用，其中，所述抗皮肤衰老通过抗氧化和/或抗糖基化实现。
  9. 一种制备如权利要求1-3中任一项所述的中药组合物的方法，所述方法包括：
    采用溶剂超声提取法分别制备西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物；
    将西红花提取物、人参提取物、荷花提取物、虎杖提取物、川芎提取物和当归提取物按照重量份数进行组合。
  10. 一种皮肤外用剂，所述皮肤外用剂包含如权利要求1-3中所述的中药组合物。
  11. 如权利要求10所述的皮肤外用剂，所述皮肤外用剂包含0.01-5重量％的如权利要求1所述的中药组合物。
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