WO2024109386A1 - Skin whitening composition capable of promoting permeation and enhancing effects - Google Patents

Skin whitening composition capable of promoting permeation and enhancing effects Download PDF

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Publication number
WO2024109386A1
WO2024109386A1 PCT/CN2023/124652 CN2023124652W WO2024109386A1 WO 2024109386 A1 WO2024109386 A1 WO 2024109386A1 CN 2023124652 W CN2023124652 W CN 2023124652W WO 2024109386 A1 WO2024109386 A1 WO 2024109386A1
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Prior art keywords
weight ratio
extract
bletilla striata
skin
chinese herbal
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PCT/CN2023/124652
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French (fr)
Chinese (zh)
Inventor
冯春波
倪向梅
贾海东
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上海家化联合股份有限公司
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Publication of WO2024109386A1 publication Critical patent/WO2024109386A1/en

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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)
    • A61K36/898—Orchidaceae (Orchid family)
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • 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
    • A61K8/67—Vitamins
    • 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
    • A61K8/9728—Fungi, e.g. yeasts
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • 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

Definitions

  • the invention relates to the fields of natural drug chemistry and cosmetics, and in particular to a traditional Chinese medicine composition with whitening, anti-oxidation and skin-lightening effects, a preparation method and application of the traditional Chinese medicine composition.
  • the current research hotspot is the role and effectiveness of the entire whitening chain, which includes but is not limited to 1) the stimulation of reactive oxygen species under the action of ultraviolet rays; 2) the activation factor that stimulates melanocytes produced in keratinocytes; 3) the stimulation pathway of melanocyte activation factor; 4) the generation of tyrosinase protein in melanocytes; 5) tyrosinase activation and its reaction chain; 6) the transfer of melanin carried by melanosomes; 7) the metabolism of melanin transferred into keratinocytes. From the perspective of the mechanism and mechanism of whitening, the above main links should be regulated to prevent possible pigmentation, spots and spots. Raw, and dull skin, etc.
  • TCM theory believes that the aging mechanism is the view that "when qi and blood are not harmonious, all diseases will arise", that is, qi deficiency and blood stasis are the root causes of aging. Modern medicine believes that qi deficiency and blood stasis are caused by poor microcirculation, poor blood fluidity, and poor metabolism inside the skin.
  • Chinese herbal medicine can regulate the balance of yin and yang, regulate qi, blood and body fluids, regulate internal organs and delay aging. Therefore, the social and economic benefits of applying Chinese herbal medicine to the development of cosmetics are promising.
  • a Chinese herbal medicine extract comprising Poria cocos, Tribulus terrestris, Ampelopsis pilosula, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni cortex has the effects of whitening, anti-oxidation and brightening skin tone, and can also be combined with additional whitening ingredients for application in cosmetics.
  • the present invention provides a whitening composition for promoting penetration and enhancing efficacy, comprising:
  • the Chinese medicine extract is prepared from the following raw materials: Poria, Tribulus, Bletilla striata, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni cortex, wherein the weight ratio of Poria: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex is 1:1-4:4-10:8-10:1-4:1-4:1-4,
  • the polyol is a mixture of butanediol and ethylhexylglycerol in a weight ratio of 9:1.
  • the whitening ingredient is selected from: niacinamide, ascorbyl glucoside or a combination thereof.
  • the weight ratio of Poria cocos:Tribulus terrestris:Bletilla striata:Paeonia lactiflora:Atractylodes macrocephala:Bletilla striata:Dictamni cortex is 1:1-2:4-8:8-10:1-4:1-4:1-2.
  • the Chinese herbal medicine extract is prepared by solvent extraction.
  • the solvent extraction adopts a water extraction and alcohol precipitation method.
  • the weight ratio of the Chinese herbal medicine extract to the polyol is 1:10.
  • the whitening composition of the present invention comprises 10-50% by weight of the Chinese herbal medicine extract.
  • the present invention also relates to a freeze-dried product of the whitening composition.
  • the present invention also relates to use of the whitening composition or freeze-dried product in skin whitening.
  • the present invention also relates to an external skin preparation comprising the whitening composition or the freeze-dried product.
  • FIG. 1 shows the HPLC spectrum of PGG of the Chinese medicine extract of Example 4.
  • FIG2 shows the results of the apparent chromaticity of the model melanin content.
  • Figure 3 shows the results of the laser Raman confocal microscopy evaluation of the permeability.
  • the left side of the figure represents Example 43, and the right side represents nicotinamide VB3.
  • the purpose of the present invention is to improve the efficacy of the traditional Chinese medicine complex by synergistic combination, increase the content of active ingredients through an extraction process, improve the special smell and color of the traditional Chinese medicine complex, improve the bioavailability of the traditional Chinese medicine complex, and combine it with modern cosmetic technology to provide a traditional Chinese medicine composite product with better skin pigmentation inhibition effect.
  • the product can be directly used on the skin and can also be added to the cosmetic formula as an effective additive, thereby greatly improving the efficacy of the cosmetic application and having a low cost.
  • the invention is based on the research results of multiple ancient books and modern Chinese herbal medicine, and multiple ancient Chinese medicine prescriptions are compounded to obtain a relatively optimal beauty prescription compounded with the theory of Chinese medicine compatibility.
  • the invention uses Poria cocos, Tribulus terrestris, Ampelopsis pilosula, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni to obtain Chinese medicine extracts.
  • the present invention uses modern Chinese herbal medicine extraction methods and processes to pre-treat the ancient Chinese medicine prescription.
  • the Chinese herbal medicine extract of the present invention includes crushing the Chinese herbal medicine raw materials before solvent extraction.
  • a high-speed universal crusher FW100 model
  • FW100 model can be used to crush the mixture of Chinese herbal medicine raw materials.
  • the present invention also utilizes concentration, purification and other processes to improve and increase the content of active substances in the Chinese medicine compound extract.
  • a Chinese medicine extraction and concentration tank (TNH type) is used to achieve concentration.
  • the present invention utilizes cosmetic technology to further improve the bioavailability of active ingredients of Chinese herbal medicine to the skin and enhance the whitening effect.
  • Peony is the dried root of Paeonia lactiflora Pall, a plant of the Ranunculaceae family. It contains paeoniflorin, paeonol, paeonin, benzoic acid, volatile oil, fatty oil, resin, tannin, sugar, starch, mucilage, protein, ⁇ -sitosterol and triterpenes.
  • Ampelopsis japonica (Thunb.) Makino is the dried root tuber of Ampelopsis japonica (Thunb.) Makino, a plant of the Vitaceae family.
  • the root tuber contains mucilage and starch.
  • Tribulus terrestris is the dried mature fruit of Tribulus terrestris L., a plant of the Tribulaceae family.
  • the roots and leaves contain saponins, and the aglycones include diosgenin, gitogenin, chlorogenin, and ruscogenin.
  • the leaves also contain kaempferol and a variety of kaempferol glycosides.
  • Atractylodes is the dried rhizome of Atractylodes macrocephala Koldz., a plant of the Asteraceae family. It contains 1.4% volatile oil, the main components of which are atractylol, atractylon, etc. It also contains vitamin A.
  • Poria cocos is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf, which contains ⁇ -Pachyman ( ⁇ -Pachyman) accounting for about 93% of the dry weight and the triterpenoid compound acetylpachymic acid (Pachymic acid). It contains 3 ⁇ -hydroxylanostane trienoic acid, ...
  • Dictamnus dasycarpus Turcz. is a dried root bark of the Rutaceae plant, containing Dictamnine, Dictamnolactone, Obaculactone, Limonin, Sitosterol, Obacunonic acid, Trigonelline, Choline, Fraxinellone. It also contains Campesterol, Skimmianin, ⁇ -Fagarin, Dasycarpamin. The above-ground part contains Psoralen and Xanthotoxin.
  • Bletilla striata is the dried tuber of Bletilla striafa (Thunb.) Reichb.f., a plant of the orchid family. Its fresh tuber contains 14.6% water, 30.48% starch, and 1.5% glucose. It also contains volatile oil and mucilage.
  • the root contains Bletilla mannan, which is a glucomannan composed of 4 parts of mannose and 1 part of glucose.
  • the formula is still based on the ingredients that nourish both yin and yang, namely Paeonia lactiflora Pall and Ampelopsis japonica (Thunb Vlakino) as the main medicines; the auxiliary medicines are Tribulus terrestris L and Atractylodes macrocephala Koidz, which are warming herbs; Poria cocos (Schw.) Wolf and Dictamnus dasycarpus Turcz are added as adjuvants; and Bletilla striata Thunb Reichb.f. is used as the guiding medicine.
  • the formula is identified with reference to the 2015 edition of the Chinese Pharmacopoeia and the Flora of China. The formula is simplified as much as possible to form a simple formula for balanced beauty, so as to meet the requirements of later extraction and purification technology.
  • This application is the first to combine Poria cocos, Tribulus terrestris, Bletilla striata, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni to extract, and the various herbs in the obtained compound Chinese medicine extract complement each other to achieve the effects of anti-glycation, anti-yellowing, whitening and brightening skin color.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1-4: 4-10: 8-10: 1-4: 1-4: 1-4.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1-4: 4-10: 8-10: 1-4: 1-4: 1-4.
  • the weight ratio of Bletilla striata: Dictamni is 1:4:10:10:1:4:4.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:2:8:10:4:1:2.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:1:10:10:4:1:1.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:1:4:10:4:1:1.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1: 4: 10: 2: 1: 1.
  • the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 2: 4: 8: 4: 1: 2.
  • the Chinese medicinal extract of the present invention can be added into cosmetics as an effective additive to achieve the effects of anti-glycation, yellowing, whitening and brightening skin tone.
  • the Chinese medicine extract of the present invention is prepared by solvent extraction.
  • Common extraction solvents include, but are not limited to, water (e.g., deionized water) and organic solvents (e.g., ethanol).
  • organic solvents e.g., ethanol
  • microwave extraction supercritical carbon dioxide extraction
  • ultrasonic extraction ultrasonic extraction
  • enzyme extraction etc.
  • the Chinese medicine extract of the present invention is prepared by water extraction and alcohol precipitation.
  • the Chinese medicine extract of the present invention is extracted by boiling with deionized water, and then precipitated with alcohol to obtain a filtrate to obtain the desired Chinese medicine extract.
  • ethanol is used in the alcohol precipitation process.
  • the extraction process of water extraction and alcohol precipitation lasts for 1-24 hours. In some embodiments, the extraction process of water extraction and alcohol precipitation lasts for 12-16 hours.
  • the Chinese medicine extract of the present invention uses alcohol as an extraction solvent.
  • the Chinese medicine extract of the present invention can be extracted with ethanol.
  • the extraction process is carried out under boiling conditions (e.g., 80 ⁇ 10 ° C).
  • 70% by volume ethanol can be used for extraction.
  • the alcohol extraction process lasts for 2-4 hours.
  • the present invention combines the Chinese herbal medicine extract with a polyol to form a post-processed product.
  • the Chinese herbal medicine extract and the polyol are combined in a weight ratio of 1:10.
  • polyol used in the present invention refers to a water-soluble polyol having two or more hydroxyl groups in the molecule, including but not limited to: glycerol, diglycerol, butylene glycol, pentanediol, propylene glycol, ethylhexylglycerol, polyethylene glycol, sorbitol, etc.
  • Polyols are commonly used as moisturizers in cosmetics, absorbing moisture from the environment, replenishing it into the skin, and increasing the water content of the skin surface. Polyols can be used alone, or they can be used in combination. For example, two or more polyols can be used in combination.
  • the herbal extract of the present invention is combined with a mixture of pentylene glycol and propylene glycol in a weight ratio of 9: 1. In some embodiments, the herbal extract of the present invention is combined with a mixture of polyethylene glycol and caprylyl glycol in a weight ratio of 5: 5.
  • the Chinese herbal extract is combined with a mixture of butylene glycol and ethylhexylglycerol in a weight ratio of 9:1.
  • the post-processed product formed by combining the Chinese herbal medicine extract with the polyol can be further combined with a whitening component to form a whitening composition.
  • Vitamin C/derivatives are safe whitening ingredients with strong antioxidant properties. They can improve facial dullness, while effectively inhibiting the activity of tyrosinase and the formation of melanin, providing a root whitening effect.
  • Nicotinamide is a water-soluble vitamin and a member of the vitamin B family. It can be converted from nicotinic acid in vivo and has a vitamin effect. Ascorbic acid 2-glucoside (AA2G) is a derivative of vitamin C and also has a vitamin effect. However, the transdermal permeability of nicotinamide and ascorbic acid 2-glucoside has always been one of the core issues that have not been resolved.
  • Combining the active ingredients ascorbyl glucoside and/or niacinamide with the post-processed product of the Chinese herbal extract and polyols of the present invention can significantly improve the gloss and transparency of the skin, making the skin "translucent white” and the surface clean and bright.
  • Whitening active ingredients, vitamin C/derivatives, and niacinamide can inhibit melanin from the source, and the combined niacinamide further cuts off the transmission of melanin to the epidermal cells of the skin to prevent spots, and at the same time can help the skin to remove endogenous yellowing and improve dullness, so that the whitening/brightening effect of the product can be maximized.
  • the present invention provides a whitening composition comprising niacinamide and/or ascorbyl glucoside.
  • the whitening composition of the present invention comprises 1-5 wt% nicotinamide. In a preferred embodiment, the whitening composition of the present invention comprises 3 wt% nicotinamide.
  • the whitening composition of the present invention comprises 0.1-2 wt% ascorbyl glucoside. In a preferred embodiment, the whitening composition of the present invention comprises 0.1-1 wt% ascorbyl glucoside.
  • the whitening composition of the present invention comprises 10-50% by weight of the post-treatment. In some embodiments, the whitening composition of the present invention comprises 10-30% by weight of the post-treatment. In some embodiments, the whitening composition of the present invention comprises 30-50% by weight of the post-treatment.
  • the present invention also relates to a freeze-dried product of a Chinese herbal medicine extract.
  • the freeze-dried product may be an amorphous powder.
  • freeze-drying is performed using a vacuum freeze dryer model FD-2 produced by Beijing Boyikang Laboratory Instrument Co., Ltd.
  • freeze drying is set at -80 to -40°C
  • vacuum degree 1 to 30Pa time 8 hours
  • sublimation drying is set at -20 to +20°C
  • vacuum degree 1 to 30Pa time 6 hours
  • water content is controlled between 0 and 6%
  • analytical drying is set at -10 to +20°C
  • vacuum degree 1 to 30Pa time 3 hours
  • water content is controlled between 0 and 6%.
  • the present invention also relates to an external skin preparation, which comprises the whitening composition of the present invention or a lyophilized product thereof, and a cosmetically, dermatologically or pharmaceutically acceptable excipient.
  • the amount of the whitening composition is 0.001-50% (w/w), preferably 1-20% (w/w), more preferably 2-10% (w/w), and most preferably 3-8% (w/w), based on the total weight of the external skin preparation.
  • the skin external application 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 may be a basic cosmetic, a facial makeup cosmetic, a body cosmetic, a hair care cosmetic, etc., and there is no particular limitation on its dosage form. It can be reasonably selected according to different purposes.
  • This skin external preparation can be formulated into any suitable product form.
  • product forms include, but are not limited to, aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions, hand-pump sprays, sticks, facial masks and wet tissues.
  • This skin external preparation can be conveniently used for preparation or as a cosmetic, dermatological or pharmaceutical topical application product by various methods well known in the art.
  • the skin topical composition of the present invention may include one or more of the following ingredients: antiallergic agents, antimicrobial agents, antioxidants, chelating agents, colorants, depigmenting agents, emollients, emulsifiers, exfoliants, film formers, fragrances, moisturizers, insect repellents, lubricants, pharmaceutically active agents, moisturizers, photostabilizers, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity regulators, vitamins or any combination thereof.
  • the cosmetic, dermatological or pharmaceutically acceptable excipients that can be used for the skin topical composition of the present invention are in the form of an aqueous phase, an oil phase, a gel, a wax-in-water emulsion, an oil-in-water emulsion or an oil-in-water emulsion.
  • the aqueous phase is a mixture of one or more water-soluble or dispersible components, which can be liquid, semi-solid or solid at room temperature (25° C.).
  • the excipient includes or can be in the form of a suspension, dispersion or solution in water or a water-alcohol excipient, which can contain a thickener or a gelling agent. Those skilled in the art can select a suitable product form based on the knowledge mastered by those skilled in the art, the components contained therein.
  • 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 a linear or branched lower monohydric alcohol containing 2 to 5 carbon atoms, such as ethanol or propanol; a polyol, 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 a linear or branched lower monohydric alcohol containing 2 to 5 carbon atoms, such as ethanol or propanol; a polyol, such as propylene glycol, sorbitol, glycerol, panthenol or polyethylene glycol, and mixtures thereof.
  • a hydrophilic organic solvent such as an alcohol, especially a linear or branched lower monohydric alcohol containing 2 to 5 carbon atom
  • composition of the invention when the composition of the invention is in the form of an emulsion, the composition may also optionally contain a surfactant.
  • the composition may also comprise a film-forming polymer, such as polyurethanes, polyacrylic acid homopolymers or copolymers, polyesters, hydrocarbon-based resins and/or silicone resins.
  • a film-forming polymer such as polyurethanes, polyacrylic acid homopolymers or copolymers, polyesters, hydrocarbon-based resins and/or silicone resins.
  • the polymer may be dissolved or dispersed in a cosmetically acceptable vehicle and optionally combined with a plasticizer.
  • composition of the present invention may also comprise an oil phase, which contains an oil-soluble or oil-dispersible component that is liquid at room temperature (25° C.) and/or an oily or waxy substance at room temperature, such as wax, semisolid, gum and a mixture thereof.
  • oil phase may also contain an organic solvent.
  • Suitable oily substances are usually liquid at room temperature and include: hydrocarbon-based oils of animal origin, such as fully hydrogenated squalene; hydrocarbon-based vegetable oils, such as liquid C4-10 fatty acid triglycerides, for example heptanoic acid or caprylic acid triglycerides, or oils, for example sunflower oil, corn oil, soybean oil, grape seed oil, castor oil, avocado oil, caprylic/capric triglycerides, jojoba oil; linear or branched hydrocarbons of mineral or synthetic origin, for example liquid paraffin and its derivatives, vaseline; synthetic esters and ethers, in particular esters of fatty alcohols, for example isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, isostearyl isostearate; hydroxylated esters, for example isostearyl lactate, hydroxy octyl stearate, octyl
  • composition of the present invention may further comprise any components commonly used in the cosmetic field. These components include preservatives, aqueous phase thickeners (extract biopolymers, synthetic polymers) and fat phase thickeners, fragrances, hydrophilic and lipophilic active agents and mixtures thereof.
  • composition of the present invention may also contain an additional particulate phase, which may be a pigment and/or pearlescent agent and/or filler used in cosmetic compositions.
  • Pigments may be present in the composition, suitable inorganic pigments include titanium, zirconium and cerium oxides as well as zinc oxide, iron oxide and ferric blue; suitable organic pigments include barium, strontium, calcium and aluminium 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, silica, zinc stearate, mica, kaolin, nylon powder, polyethylene powder, Teflon, starch, boron nitride, copolymer microspheres, such as silicone resin microspheres.
  • the oil phase of the composition of the present invention may comprise one or more waxes, gums or mixtures thereof.
  • the waxes include hydrocarbon-based waxes, fluoro waxes and/or silicone waxes and may be derived from plant, mineral, animal and/or synthetic sources. Suitable waxes include beeswax, carnauba wax, candelilla wax, paraffin wax, microcrystalline wax, ozokerite wax; synthetic waxes include polyethylene wax, silicone wax containing C16-45.
  • Gums are generally polydimethylsiloxane or sodium carboxymethylcellulose or extracts, and semi-solid substances are generally hydrocarbon-based compounds, such as lanolin and its derivatives.
  • composition of the present invention can be formulated into any suitable product form.
  • product forms include, but are not limited to, aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions, hand-pump sprays, sticks, facial masks, and wet wipes.
  • the composition of the present invention can be conveniently used to prepare or as a cosmetic, dermatological, or pharmaceutical topical application product by various methods well known in the art.
  • the skin topical composition of the present invention may include one or more of the following ingredients: antiallergic agents, antimicrobial agents, antioxidants, chelating agents, colorants, depigmenting agents, emollients, emulsifiers, exfoliants, film formers, fragrances, moisturizers, insect repellents, lubricants, pharmaceutically active agents, moisturizers, photostabilizers, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity regulators, vitamins or any combination thereof.
  • the medicinal raw materials used in the following examples were all purchased from “Anhui Bozhou Jingwan Chinese Medicine Pieces Factory", and the incoming materials were in the form of "Chinese herbal medicine pieces”; the biological reagents used were all purchased from Shanghai Jahwa Biotechnology Co., Ltd.
  • Tribulus terrestris Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in a weight ratio of 1:1:10:10:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract.
  • the above extract was dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
  • the above extract is dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
  • Tribulus terrestris Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in a weight ratio of 1:2:4:8:4:1:0, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract.
  • the above extract was dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
  • Tribulus terrestris Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:0:8:4:1:0, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract.
  • the extracts of the Chinese medicinal compound of Examples 1 to 40 were taken to detect the content of active ingredients therein.
  • active drug ingredients The chemical structure of active drug ingredients is the key to drug transdermal penetration. Fat-soluble drugs easily penetrate the stratum corneum, skin barrier, and cell membrane, but diffuse slowly in the active epidermis due to the relatively high water content. Water-soluble drugs penetrate the stratum corneum cell membrane and skin barrier slowly, but diffuse quickly in the active epidermis. Generally, when selecting active ingredients for functional drugs, attention is paid to the molecular structure of the ingredients, and drug ingredients with a moderate oil/water distribution are selected as much as possible, or water-soluble and fat-soluble ingredients are used together, which often achieves better results.
  • 1,2,3,4,6-O-Galloylglucose is a polyphenolic compound composed of 5 It is composed of ester acid and one glucose through an ester bond, with a relative molecular weight of 940. It has good hydrophilicity and lipophilicity and strong physiological activity, such as anti-tumor, anti-oxidation, anti-leukemia, anti-allergy, and hypoglycemic functions. It exists in many Chinese medicinal materials.
  • Preparation of reference solution accurately weigh the PGG reference substance dried to constant weight, add methanol to make a mixed solution containing 0.2 mg per 1 mL, and shake well.
  • Table 1 PGG content in Chinese herbal extracts of Examples 1 to 40
  • the Chinese herbal compound extracts of Examples 1 to 6 obtained a higher amount of PGG, especially Example 2, which reached 0.4006 mg/ml, 96% higher than Example 6.
  • the alcohol extraction process even with the same compatibility ratio of Chinese herbal medicines, has a lower content of active ingredient PGG as a whole, especially Example 8 with the same ratio, which is about 13.7% lower than Example 2; similarly, in the water extraction and alcohol precipitation process of Examples 1 to 6, even with the same ratio and compatibility, the overall PGG content is higher than that of the alcohol extraction process of Examples 7 to 12.
  • the PGG content obtained by water extraction and alcohol precipitation or alcohol extraction process is generally lower than that of the seven herbs co-existing, such as Example 14, where PGG was not detected. Comparing the PGG content obtained in Example 2 with that obtained in Examples 13 to 40, it is basically between 2 and 100 times; in general, the seven different Chinese herbal medicines obtained by combining in different proportions have large differences in active substance content between different combinations and proportions, and there are also large differences in active substance content for different extraction processes.
  • Test Example 2 Whitening efficacy test based on melanin model
  • the 3D melanin skin model used in this test ( Batch number: MS220304, Guangdong Dongboxi Biotechnology Co., Ltd.) prepared a 6-well plate, added 3.7 mL of M-TA culture medium to each well, and transferred the model on the third day of gas-liquid surface culture, that is, the day the model was received (Day 0), to the marked 6-well plate; each test group required 6 models (for the determination of apparent chromaticity, L*b* value and melanin content), and all 6-well plates with models were transferred to a CO 2 incubator for culture (37°C, 5% CO 2 ). UVB (50 mJ/cm 2 ) was used as the stimulus condition.
  • the colorimetric card was placed directly below the SLR camera, and a single model was placed in the color circle of the colorimetric card with tweezers to take a photo.
  • the SLR camera parameters were set to manual photography mode, the focal length was adjusted to 5.8 mm, the aperture was set to f/8, the aperture was adjusted to F22, the shutter speed was set to 1/80s, and the ISO was set to 1600.
  • L* value and b* value test the model after the apparent chromaticity test was completed, the L* value and b* value test were performed.
  • the specific detection operation is as follows: Place the model on a flat and hard white surface with the stratum corneum facing upwards.
  • the instructions for use of the colorimeter align the detection hole of the colorimeter vertically with the surface of the model for detection. Repeat the reading for each model three times and record the data. Take the average value as the L* value and b* value reading of the single model.
  • the tested model is placed in a clean EP tube for melanin content determination.
  • Melanin content test 1) Place the model in a 1.5mL EP tube, label it, add 1mL PBS buffer to each tube, vortex on a vortex oscillator for 3 minutes, centrifuge at 2000r/min at a low temperature and high speed centrifuge for 10 minutes, and discard the supernatant; 2) Add 200 ⁇ L of distilled water, 500 ⁇ L of anhydrous ethanol and 500 ⁇ L of ether to the EP tube in step (1) in sequence, mix thoroughly, let stand at room temperature for 20 minutes, and centrifuge at 3000r/min.
  • Table 3 Whitening efficacy (melanin content) results of Examples 41 to 112 based on the melanin model
  • the core factors affecting skin "transparency”, “brightness” and “whiteness” include 1) the content of melanin in the skin; 2) (endogenous) dark yellowing of the skin base; 3) skin inflammation caused by oxidative factors; 4) skin barrier function and water content; According to research on factors affecting the dark yellowing and dullness of Chinese women's skin, with increasing age, the facial brightness of Chinese women decreases significantly, and the yellowness increases significantly. Dark yellowing is a characteristic change that distinguishes Chinese women from Caucasian women and Mexican women.
  • the main factors affecting "dark” and “yellow” skin are the synthesis of melanin and protein carbonylation, respectively. Both reactions can be induced by oxidative stress. Under normal physiological conditions, the body has a complete antioxidant defense mechanism.
  • Vitamin C/derivatives are safe whitening ingredients with strong antioxidant properties. They can improve facial dullness, while effectively inhibiting the activity of tyrosinase and the formation of melanin, providing a root whitening effect.
  • Nicotinamide is a water-soluble vitamin, which is a member of the vitamin B family. It can be converted from nicotinic acid in vivo, and both have vitamin effects. However, nicotinic acid is prone to cause a series of problems such as skin itching, redness and allergies, so the present invention uses more than 99% high-purity nicotinamide to avoid the mixing of nicotinic acid to the greatest extent. Nicotinamide can effectively prevent the transmission of melanin, thereby bringing whitening and spot-lightening effects. In the literature, it is reported that the use of vitamin C combined with nicotinamide has achieved relatively satisfactory results in the treatment of chloasma.
  • the two can cause an increase in the level of endogenous antioxidant NAD(P)H, which has the effect of helping the skin to resist glycation in the deep layer, thereby endogenously regulating the skin's dark yellowing phenomenon.
  • NAD(P)H endogenous antioxidant
  • the transdermal permeability of niacinamide combined with AA2G has always been one of the core issues that have not been resolved.
  • the first thing that needs to be studied to realize the core efficacy of Chinese herbal cosmetics is the transdermal absorption and utilization of active ingredients.
  • the keratinocytes are arranged more tightly, which reduces the effective penetration area of the skin and the space for substances to penetrate the skin, thereby reducing the degree and efficiency of transdermal absorption of drugs.
  • the first thing to do for functional cosmetics is to restore the water content of the skin to a normal level or a moist state.
  • the stratum corneum contains 10% or more water, and the other layers of the epidermis contain 10% to 47%.
  • This invention is the first to combine the highly effective moisturizing ingredients, small molecule polyols (butylene glycol) and ethylhexylglycerin, to moisturize the skin, strengthen the skin barrier, and increase the moisture content of the skin.
  • Butylene glycol is a A classic functional moisturizing ingredient
  • butylene glycol is a small molecule with a molecular weight of only 90g/mol. It has good skin moisturizing and permeability.
  • the "twin""permeation” technology combining ethylhexylglycerin and butylene glycol can help the skin achieve double penetration and significantly increase the moisturizing effect, which can significantly increase the penetration effect of active ingredients.
  • Double-effect moisturizing, fast water retention, water lock, bright and white skin can significantly improve the gloss and transparency of the skin. It is the "translucent white" essence of the skin, with a uniform and translucent surface. Whitening Chinese herbal active ingredients, vitamin C/derivatives, and niacinamide can inhibit melanin from the source and resist oxidation. Niacinamide can further cut off the transmission of melanin to the epidermal cells of the skin to prevent spots. At the same time, it can help the skin to remove yellowness endogenously and improve dullness, so that the whitening/translucent effect of the product can be maximized.
  • Examples 41 to 112 From the results of Examples 41 to 112 (see Table 3), most of the examples and compositions have the effect of inhibiting melanin. From the perspective of relative improvement rate, the preferred combination of 7 Chinese herbal medicines improves by more than 12%, which is also positively correlated with the content of PGG in the extracts of the same examples. Examples 2, 4, 8, and 10 are post-processed products of preferred Chinese herbal extracts. By compounding with specific whitening ingredients, the improvement rate of the example extracts in inhibiting melanin content is greatly improved, such as Example 43 increased to 50.67%, Example 44 increased to 46.27%, Example 54 increased to 42.41%, and Example 62 increased to 50%. The average improvement ratio exceeds 30%, indicating that the use of the selected two substances for compounding can greatly improve the efficacy of the Chinese herbal compound extract in inhibiting melanin content.
  • Example 43 is significantly improved compared with NC and PC.
  • Test Example 3 Permeability test based on laser Raman confocal method
  • a confocal Raman microscope system (Thermo, DXR2Xi model) equipped with a 532nm (He-Ne laser) laser source, a semiconductor-cooled CCD detector (1024 ⁇ 800 pixels) and a 25 ⁇ m confocal pinhole was used; the laser beam was used with a 50x telephoto objective (NA 0.50BD) to obtain sample parameters.
  • NA 0.50BD 50x telephoto objective
  • a standard single-point calibration was performed using Raman scattered rays generated by a silicon plate (520.5cm -1 ). All spectra were collected in the range of 50 to 3400cm -1 .
  • the Raman spectrum of each point was obtained by XY scanning.
  • the laser power for scanning the sample was 3.5mW, and the integration time for each point of the spectrum was 0.05sec.
  • All Raman spectral data were preprocessed (cosmic ray removal, background removal, smoothing and noise reduction). Raman images were obtained by using XZ Raman deep imaging. The experiment started with single spectrum acquisition. After obtaining a single spectrum, the single spectrum was first preprocessed and the spectral quality was evaluated to explore the experimental conditions. Subsequently, a point-by-point scanning method was used for depth scanning imaging. The spectral data was collected with a step size of 2 ⁇ m, a scanning area of 8 ⁇ m ⁇ 100 ⁇ m (4 ⁇ 50 pixels), and a spectral integration time of 0.05 seconds for each pixel.
  • spectra were recorded by OMSNIC of Thermo Fisher SCIENTIFIC for data processing. Data were analyzed using R (i386 4.0.3). Raman spectra were baseline corrected, SG second-order smoothed, and normalized before statistical analysis; K-means clustering was used to analyze spectral changes in Raman imaging profiles. K-means is a data processing method that classifies spectral data based on the similarity of spectral data. Each spectrum is regarded as a point in a two-dimensional space, so the similarity between spectra can be mathematically defined by similarity coefficients and distances. First, the number of clusters k is set, and the spectra to be clustered are divided into k categories.
  • K-means clustering starts with a random cluster distribution of k clusters, and then iteratively solves them according to their minimum distance to the average spectrum of the cluster. This work is carried out until a stable arrangement is reached, and a color map is constructed to more clearly observe the differences in skin tissue with depth.
  • the advantages of this algorithm are fast calculation speed, simple process, and wide applicability. In order to obtain reliable results, the collected Raman spectra must be preprocessed, including removing cosmic rays, removing baseline background, and smoothing and reducing noise.
  • the Raman spectra must be preprocessed. Because during the measurement process, there will be interference from fluorescence background, cosmic rays, and Gaussian noise or Poisson noise, which will affect the collection and In order to obtain undisturbed data, these influencing factors must be eliminated, so baseline correction is required. After baseline correction, the spectrum is smoothed, and the Savitzky-Golay filter (convolution fitting algorithm based on least squares) is used to smooth the spectral mechanical energy.
  • the Savitzky-Golay filter convolution fitting algorithm based on least squares
  • the skin tissue used in the experimental test (six weeks, male suckling pig abdomen, purchased from Chongqing Meisheng Trading Co., Ltd.).
  • the purchased suckling pig abdomen skin was frozen and stored in a refrigerator at -25°C.
  • the size of the skin sample was maintained at 1.5 ⁇ 1.5cm 2. During the entire experimental measurement process, the lower end of the skin sample was always in contact with the PBS buffer.
  • Example 43 The laser Raman confocal penetration performance of Example 43 was tested and evaluated, and compared with the solution of the whitening ingredient preferred by the patent of the present invention (i.e., VB3 of the same concentration), the results are shown in Figure 3.
  • Figure 3 is a direct presentation of the Raman spectrum, with the scale of skin depth (leftmost) and the maximum and minimum directions of the degree scale added. It can be seen from the scale that yellow indicates maximum penetration and blue indicates minimum penetration. On the cross-section of the skin, it is from the skin surface to the deep layer of the skin, i.e., 0-100 ⁇ m.
  • the substance can basically penetrate to a depth of 60-100 ⁇ m; compared with the picture on the right, it can be seen that after 120 minutes, most of the substance still remains in the skin surface layer of 0-20 ⁇ m.
  • Example 43 the penetration efficiency of Example 43 is significantly improved, that is, within the same period of time, the penetration efficiency of the whitening component in Example 43 is higher and the penetration is deeper.
  • the main active ingredients in Chinese herbal compound additives are flavonoids, polyphenols, polysaccharides, etc.
  • the distribution and content of specific components mostly depend on the extraction method and means.
  • Advanced freeze-drying technology can also be used in the later stage of the preparation process to better retain the active ingredients in the extract, and to retain the original flavor of the active ingredients to a greater extent, especially Heat-sensitive active ingredients.
  • some easily oxidized active ingredients (such as oils) can also be protected because of the vacuum and oxygen-free operation. When operated under vacuum and low temperature, the growth of microorganisms and enzyme action are inhibited. It can be stored for a long time at room temperature without adding any preservatives, reducing microbial erosion and extending the shelf life of the product.
  • the skin external preparation is preferably a cosmetic composition, such as a toner, an essence, a cream, etc.
  • the weight percentage of the composite extract in the skin external preparation is 0.001%-50% (w/w).
  • the preferred weight percentage is 1%-20% (w/w).
  • the more preferred weight percentage is 2%-10% (w/w).
  • the most preferred weight percentage is 3%-8% (w/w).
  • Embodiments 82 to 121 of the present invention can also be used alone as low-temperature freeze-dried products.
  • the cosmetics prepared by using the composition of the present invention have the same or better use effects as the commercially available products.
  • the present invention illustrates the detailed method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed method, that is, it does not mean that the present invention must rely on the above-mentioned detailed method to be implemented.
  • Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

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Abstract

Provided is a skin whitening composition capable of promoting permeation and enhancing effects, comprising: a skin whitening component, a traditional Chinese medicine extract, and polyol. The traditional Chinese medicine extract is prepared from the following raw materials: poria cocos, tribulus terrestris, radix ampelopsis, paeonia lactiflora pall, largehead atractylodes rhizome, bletilla striata, and cortex dictamni. The poria cocos, the tribulus terrestris, the radix ampelopsis, the paeonia lactiflora pall, the largehead atractylodes rhizome, the bletilla striata, and the cortex dictamni are in a weight ratio of 1:1-4:4-10:8-10:1-4:1-4:1-4. The polyol is a mixture of butanediol and ethylhexylglycerin in a weight ratio of 9:1.

Description

促渗增效的美白组合物Whitening composition with enhanced penetration and synergy 技术领域Technical Field
本发明涉及天然药物化学领域和化妆品领域，具体涉及一种用于美白、抗氧化、提亮肤色功效的中药组合物，该中药组合物的制备方法以及应用。The invention relates to the fields of natural drug chemistry and cosmetics, and in particular to a traditional Chinese medicine composition with whitening, anti-oxidation and skin-lightening effects, a preparation method and application of the traditional Chinese medicine composition.
背景技术Background technique
中医药是中华民族的瑰宝，数千年来为中华民族的繁荣昌盛做出了不可磨灭的贡献，并越来越受到世界人民的关注和重视。但由于传统中医药理论与现代科学理论脱节以及中药研究手段相对落后，使中药资源的开发和利用受到极大的影响和限制。中药的开发目前主要局限于从现有中药中寻找有效成分，并发展各种提取的手段富集和优化有效成分。而以现有中药资源为基础提升中药的开发潜力、应用效率和新的应用场景，目前尚未引起人们的广泛重视，特别是将传统中药的优势与现代化妆品组方技术相结合，实现中药的现代化是促进中药发展的重要手段。Traditional Chinese medicine is a treasure of the Chinese nation. It has made indelible contributions to the prosperity of the Chinese nation for thousands of years and has received more and more attention and attention from people around the world. However, due to the disconnection between traditional Chinese medicine theory and modern scientific theory and the relatively backward research methods of Chinese medicine, the development and utilization of Chinese medicine resources have been greatly affected and restricted. The development of Chinese medicine is currently mainly limited to finding effective ingredients from existing Chinese medicines and developing various extraction methods to enrich and optimize effective ingredients. However, improving the development potential, application efficiency and new application scenarios of Chinese medicine based on existing Chinese medicine resources has not yet attracted widespread attention. In particular, combining the advantages of traditional Chinese medicine with modern cosmetic formulation technology to realize the modernization of Chinese medicine is an important means to promote the development of Chinese medicine.
现代中草药化妆品以其秉承中医智慧，处处体现整体观念，采用的符合中草药组分不仅加强了中草药化妆品的功能性，还使得其具有一专多能的特性，并且具有天然属性，即安全性高，毒副作用小、易于利用吸收等特点具有广阔的开发应用前景。随着社会的进步和科技的发展，人们对肌肤的问题的认识不断加深，如衰老的机制、美白的机制、敏感的机制等，国人都信奉拥有白皙、光泽佳、透亮的肌肤可以遮盖容颜的衰老。Modern Chinese herbal cosmetics, with their adherence to the wisdom of traditional Chinese medicine and holistic concepts, use Chinese herbal ingredients that not only enhance the functionality of Chinese herbal cosmetics, but also make them multifunctional, and have natural properties, i.e., high safety, low toxicity and side effects, and easy to utilize and absorb, etc., which have broad development and application prospects. With the progress of society and the development of science and technology, people's understanding of skin problems continues to deepen, such as the mechanism of aging, whitening mechanism, sensitive mechanism, etc. Chinese people believe that having fair, shiny, and translucent skin can cover the aging of the face.
当今研究的热点是美白全链路的作用和起效，全链路包括但不限于1)在紫外线作用下的活性氧的激发；2)在角质形成细胞内产生的激发黑色素细胞的活化因子；3)黑色素细胞活化因子的激发路径；4)黑色素细胞内络氨酸酶蛋白的生成；5)络氨酸酶活化及其反应链路；6)黑色素小体携带黑色素的转移；7)转入角质形成细胞内的黑色素的新陈代谢；从美白的机制和机理角度来说，要对以上的主要链路进行调控，防止可能的色素沉着、色斑和斑点的产 生、以及肌肤暗沉等。The current research hotspot is the role and effectiveness of the entire whitening chain, which includes but is not limited to 1) the stimulation of reactive oxygen species under the action of ultraviolet rays; 2) the activation factor that stimulates melanocytes produced in keratinocytes; 3) the stimulation pathway of melanocyte activation factor; 4) the generation of tyrosinase protein in melanocytes; 5) tyrosinase activation and its reaction chain; 6) the transfer of melanin carried by melanosomes; 7) the metabolism of melanin transferred into keratinocytes. From the perspective of the mechanism and mechanism of whitening, the above main links should be regulated to prevent possible pigmentation, spots and spots. Raw, and dull skin, etc.
中医理论体系与分子生物学虽然属于两种不同的思想体系，但研究生命活动的物质基础是一致的，是人类关于生命与健康在不同程度上的认识和探索的产物。比如中医理论认为衰老机理是“气血不和，百病乃变化而生”的观点，即气虚血瘀是衰老的根本原因。现在医学认为气虚血瘀表现为微循环不畅、血液流动性不佳、肌肤内部的代谢不佳造成的。因此，从分子水平研究中医理论及中医药，并将中医理论及现代中医药的其他新成果应用到现代生物学技术中去，对推动中西医结合、促进医药在美容护肤方面的发展具有重要的意义。从现代医学研究来看，中草药中含有丰富的蛋白质、脂质、氨基酸、多糖类、果胶、维生素、微量元素、有机酸、生物碱、皂苷等营养物质，具有促进细胞增殖代谢，改善皮肤微循环，增强机体抗氧化能力，抗击紫外线损伤，抑制美白链路反应，保湿和皮肤屏障修护等护肤功效。中医的观点则对中草药调理阴阳平衡，调理气血津液，调理脏腑和延缓衰老等功能，故中草药应用于化妆品开发的社会和经济效益前景广阔。Although the TCM theory system and molecular biology belong to two different thought systems, the material basis for studying life activities is the same, and they are the products of human understanding and exploration of life and health to varying degrees. For example, TCM theory believes that the aging mechanism is the view that "when qi and blood are not harmonious, all diseases will arise", that is, qi deficiency and blood stasis are the root causes of aging. Modern medicine believes that qi deficiency and blood stasis are caused by poor microcirculation, poor blood fluidity, and poor metabolism inside the skin. Therefore, studying TCM theory and TCM from the molecular level and applying TCM theory and other new achievements of modern TCM to modern biological technology are of great significance to promoting the integration of Chinese and Western medicine and the development of medicine in beauty and skin care. From the perspective of modern medical research, Chinese herbal medicines are rich in nutrients such as proteins, lipids, amino acids, polysaccharides, pectin, vitamins, trace elements, organic acids, alkaloids, saponins, etc., which have skin care effects such as promoting cell proliferation and metabolism, improving skin microcirculation, enhancing the body's antioxidant capacity, resisting ultraviolet damage, inhibiting whitening link reactions, moisturizing and repairing the skin barrier. From the perspective of traditional Chinese medicine, Chinese herbal medicine can regulate the balance of yin and yang, regulate qi, blood and body fluids, regulate internal organs and delay aging. Therefore, the social and economic benefits of applying Chinese herbal medicine to the development of cosmetics are promising.
本发明意外地发现，包含茯苓、蒺藜、白蔹、芍药、白术、白芨、白鲜皮的中药提取物具有美白、抗氧化、提亮肤色的功效，还能够与额外的美白成分组合应用于化妆品中。The present invention unexpectedly discovered that a Chinese herbal medicine extract comprising Poria cocos, Tribulus terrestris, Ampelopsis pilosula, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni cortex has the effects of whitening, anti-oxidation and brightening skin tone, and can also be combined with additional whitening ingredients for application in cosmetics.
发明内容Summary of the invention
一方面，本发明提供了一种促渗增效的美白组合物，包含：In one aspect, the present invention provides a whitening composition for promoting penetration and enhancing efficacy, comprising:
美白成分；Whitening ingredients;
中药提取物；和Chinese herbal medicine extracts; and
多元醇，Polyol,
其中，所述中药提取物通过以下原料制备得到：茯苓、蒺藜、白蔹、芍药、白术、白芨和白鲜皮，其中，茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1-4∶4-10∶8-10∶1-4∶1-4∶1-4，The Chinese medicine extract is prepared from the following raw materials: Poria, Tribulus, Bletilla striata, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni cortex, wherein the weight ratio of Poria: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex is 1:1-4:4-10:8-10:1-4:1-4:1-4,
其中，所述多元醇是重量比为9∶1的丁二醇和乙基己基甘油的混合物。The polyol is a mixture of butanediol and ethylhexylglycerol in a weight ratio of 9:1.
在优选的实施方式中，所述美白成分选自：烟酰胺、抗坏血酸葡糖苷或它们的组合。 In a preferred embodiment, the whitening ingredient is selected from: niacinamide, ascorbyl glucoside or a combination thereof.
在优选的实施方式中，茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1-2∶4-8∶8-10∶1-4∶1-4∶1-2。In a preferred embodiment, the weight ratio of Poria cocos:Tribulus terrestris:Bletilla striata:Paeonia lactiflora:Atractylodes macrocephala:Bletilla striata:Dictamni cortex is 1:1-2:4-8:8-10:1-4:1-4:1-2.
在优选的实施方式中，中药提取物通过溶剂提取制备得到。在更优选的实施方式中，所述溶剂提取采用水提醇沉方法。In a preferred embodiment, the Chinese herbal medicine extract is prepared by solvent extraction. In a more preferred embodiment, the solvent extraction adopts a water extraction and alcohol precipitation method.
在优选的实施方式中，中药提取物与多元醇的重量比为1∶10。In a preferred embodiment, the weight ratio of the Chinese herbal medicine extract to the polyol is 1:10.
在优选的实施方式中，本发明的美白组合物包含10-50重量％的中药提取物。In a preferred embodiment, the whitening composition of the present invention comprises 10-50% by weight of the Chinese herbal medicine extract.
另一方面，本发明还涉及美白组合物的冻干产品。In another aspect, the present invention also relates to a freeze-dried product of the whitening composition.
又一方面，本发明还涉及美白组合物或冻干产品在皮肤美白中的应用。In yet another aspect, the present invention also relates to use of the whitening composition or freeze-dried product in skin whitening.
再一方面，本发明还涉及一种皮肤外用剂，所述皮肤外用剂包含美白组合物或冻干产品。In yet another aspect, the present invention also relates to an external skin preparation comprising the whitening composition or the freeze-dried product.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
下面结合附图进一步说明本发明。The present invention is further described below in conjunction with the accompanying drawings.
图1显示了实施例4中药提取物的PGG的HPLC图谱。FIG. 1 shows the HPLC spectrum of PGG of the Chinese medicine extract of Example 4.
图2显示了模型黑素含量的表观色度的结果。FIG2 shows the results of the apparent chromaticity of the model melanin content.
图3显示了激光拉曼共聚焦对渗透性能的评价结果。左侧的图代表实施例43，右侧代表烟酰胺VB3。Figure 3 shows the results of the laser Raman confocal microscopy evaluation of the permeability. The left side of the figure represents Example 43, and the right side represents nicotinamide VB3.
发明详述DETAILED DESCRIPTION OF THE INVENTION
本发明目的基于中药古方复合物，在协同搭配提升功效的同时，经过萃取工艺提高活性成分含量，改善中药复合物的特殊气味和颜色，改善中药复合物的生物利用度，并与现代化妆品学技术相结合，提供一种具有较好的抑制肌肤色素沉着作用的中药复合产物，可直接用于皮肤，也可作为功效添加剂加入到化妆品配方中使用，大幅提升化妆品应用的功效，且成本较低。The purpose of the present invention is to improve the efficacy of the traditional Chinese medicine complex by synergistic combination, increase the content of active ingredients through an extraction process, improve the special smell and color of the traditional Chinese medicine complex, improve the bioavailability of the traditional Chinese medicine complex, and combine it with modern cosmetic technology to provide a traditional Chinese medicine composite product with better skin pigmentation inhibition effect. The product can be directly used on the skin and can also be added to the cosmetic formula as an effective additive, thereby greatly improving the efficacy of the cosmetic application and having a low cost.
本发明根据多部古书籍和现代中草药学的研究成果，对多个中药古方进行复合得到较优复合中医配伍理论的美容方剂。本发明采用茯苓、蒺藜、白蔹、芍药、白术、白芨和白鲜皮得到中药提取物。 The invention is based on the research results of multiple ancient books and modern Chinese herbal medicine, and multiple ancient Chinese medicine prescriptions are compounded to obtain a relatively optimal beauty prescription compounded with the theory of Chinese medicine compatibility. The invention uses Poria cocos, Tribulus terrestris, Ampelopsis pilosula, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni to obtain Chinese medicine extracts.
本发明利用现代中草药萃取方法和工艺对中药古方进行前处理。在优选的实施方式中，本发明中药提取物在溶剂提取之前包括将中草药原料进行粉碎。例如，可以采用高速万能粉碎机(FW100型)粉碎中草药原料的混合物。The present invention uses modern Chinese herbal medicine extraction methods and processes to pre-treat the ancient Chinese medicine prescription. In a preferred embodiment, the Chinese herbal medicine extract of the present invention includes crushing the Chinese herbal medicine raw materials before solvent extraction. For example, a high-speed universal crusher (FW100 model) can be used to crush the mixture of Chinese herbal medicine raw materials.
本发明还利用浓缩、纯化等工艺，改善和提升中药复合物提取物中活性物含量。在一些实施方式中，采用中药材提取浓缩罐(TNH型)实现浓缩。The present invention also utilizes concentration, purification and other processes to improve and increase the content of active substances in the Chinese medicine compound extract. In some embodiments, a Chinese medicine extraction and concentration tank (TNH type) is used to achieve concentration.
本发明利用化妆品技术，进一步改善肌肤对于中草药活性成分的生物利用度，提升美白效果。The present invention utilizes cosmetic technology to further improve the bioavailability of active ingredients of Chinese herbal medicine to the skin and enhance the whitening effect.
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。Unless otherwise defined, all scientific and technical terms used herein have the same meaning as those commonly understood by those of ordinary skill in the art to which the present invention belongs. In addition, all publications, patent applications, patents and other references mentioned herein are incorporated herein by reference. Unless otherwise indicated, percentages refer to weight percentages.
中草药药材Chinese herbal medicine
芍药为毛茛科植物芍药Paeonia lactiflora Pall的干燥根，含有根含芍药甙(Paeoniflorin)、牡丹酚(Paeonol)、芍药花甙(Paeonin)，苯甲酸、挥发油、脂肪油、树脂、鞣质、糖、淀粉、粘液质、蛋白质、β-谷甾醇和三萜类等。Peony is the dried root of Paeonia lactiflora Pall, a plant of the Ranunculaceae family. It contains paeoniflorin, paeonol, paeonin, benzoic acid, volatile oil, fatty oil, resin, tannin, sugar, starch, mucilage, protein, β-sitosterol and triterpenes.
白蔹为葡萄科植物白蔹Ampelopsis japonica(Thunb.)Makino的干燥块根，根块含粘质和淀粉。Ampelopsis japonica (Thunb.) Makino is the dried root tuber of Ampelopsis japonica (Thunb.) Makino, a plant of the Vitaceae family. The root tuber contains mucilage and starch.
蒺藜为蒺藜科植物蒺藜Tribulus terrestris L.的干燥成熟果实。根和叶含皂甙，甙元有薯蓣皂甙元(Diosgenin)、芰脱皂甙元(Gitogenin)、绿莲皂甙元(Chlorogenin)、罗斯考皂甙元(Ruscogenin)。叶尚含山柰酚(Kaempferol)和多种山柰酚甙。Tribulus terrestris is the dried mature fruit of Tribulus terrestris L., a plant of the Tribulaceae family. The roots and leaves contain saponins, and the aglycones include diosgenin, gitogenin, chlorogenin, and ruscogenin. The leaves also contain kaempferol and a variety of kaempferol glycosides.
白术为菊科植物白术Atractylodes macrocephala Koldz.的干燥根茎，含挥发油1.4％，主要成分为苍术醇(Atractylol)、苍术酮(Atractylon)等，并含有维生素A。Atractylodes is the dried rhizome of Atractylodes macrocephala Koldz., a plant of the Asteraceae family. It contains 1.4% volatile oil, the main components of which are atractylol, atractylon, etc. It also contains vitamin A.
茯苓为多孔菌科真菌茯苓Poria cocos(Schw.)Wolf的干燥菌核，含β-茯苓聚糖(β-Pachyman)约占干重93％和三萜类化合物乙酰茯苓酸(Pachymic  acid)、茯苓酸(Tumulosic acid)、3β-羟基羊毛甾三烯酸[3β-Hydroxylanosta-7，9(11)，24-trien-21-oil acid]。此外，尚含树胶、甲壳质、蛋白质、脂肪、甾醇、卵磷脂、葡萄糖、腺嘌呤、组氨酸、胆碱、β-茯苓聚糖分解酶、脂肪酶、蛋白酶等。Poria cocos is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf, which contains β-Pachyman (β-Pachyman) accounting for about 93% of the dry weight and the triterpenoid compound acetylpachymic acid (Pachymic acid). It contains 3β-hydroxylanostane trienoic acid, ...
白鲜为芸香科植物白鲜Dictamnus dasycarpus Turcz.的干燥根皮，含白鲜碱(Dictamnine)、白鲜内酯(Dictamnolactone，Obaculactone，Limonin)、谷甾醇(Sitosterol)、黄柏酮酸(Obacunonic acid)、胡芦巴碱(Trigonelline)、胆碱(Choline)、梣皮酮(Fraxinellone)。尚含菜油甾醇(Campesterol)、茵芋碱(Skimmianin)、γ-崖椒碱(γ-Fagarin)、白鲜明碱(Dasycarpamin)。地上部分含有补骨脂素(Psoralen)和花椒毒素(Xanthotoxin)。Dictamnus dasycarpus Turcz. is a dried root bark of the Rutaceae plant, containing Dictamnine, Dictamnolactone, Obaculactone, Limonin, Sitosterol, Obacunonic acid, Trigonelline, Choline, Fraxinellone. It also contains Campesterol, Skimmianin, γ-Fagarin, Dasycarpamin. The above-ground part contains Psoralen and Xanthotoxin.
白芨为兰科植物白及Bletilla striafa(Thunb.)Reichb.f.的干燥块茎，其新鲜块茎含水分14.6％、淀粉30.48％，葡萄糖1.5％。又含挥发油、粘液质。根含白及甘露聚糖(Bletilla mannan)，是由4份甘露糖和1份葡萄糖组成的葡配甘露聚糖。Bletilla striata is the dried tuber of Bletilla striafa (Thunb.) Reichb.f., a plant of the orchid family. Its fresh tuber contains 14.6% water, 30.48% starch, and 1.5% glucose. It also contains volatile oil and mucilage. The root contains Bletilla mannan, which is a glucomannan composed of 4 parts of mannose and 1 part of glucose.
遵循中药美容古方配伍的组方思路，仍然以阴阳共养之物为底，即芍药(Paeonia lactiflora Pall)、白蔹(Ampelopsis japonica(Thunb Vlakino)为君药；臣药则分别配伍温煦之蒺藜(Tribulus terrestris L)、白术(Atractylodes macrocephala Koidz)中草药；另加佐药茯苓(Poria cocos(Schw.)Wolf)、白鲜(Dictamnus dasycarpus Turcz)；使药为白芨(Bletilla striata Thunb Reichb.f.)。参考2015版《中国药典》一部，与中国植物志等内容进行鉴定。组方尽量精简，组成平衡美肌之简方，以符合后期提取、纯化技术等工艺需求。Following the idea of traditional Chinese medicine beauty formula, the formula is still based on the ingredients that nourish both yin and yang, namely Paeonia lactiflora Pall and Ampelopsis japonica (Thunb Vlakino) as the main medicines; the auxiliary medicines are Tribulus terrestris L and Atractylodes macrocephala Koidz, which are warming herbs; Poria cocos (Schw.) Wolf and Dictamnus dasycarpus Turcz are added as adjuvants; and Bletilla striata Thunb Reichb.f. is used as the guiding medicine. The formula is identified with reference to the 2015 edition of the Chinese Pharmacopoeia and the Flora of China. The formula is simplified as much as possible to form a simple formula for balanced beauty, so as to meet the requirements of later extraction and purification technology.
中药提取物Chinese herbal medicine extract
本申请首次将茯苓、蒺藜、白蔹、芍药、白术、白芨和白鲜皮组合进行提取物，得到的复方中药提取物中各味药之间相辅相成，以达到抗糖化、祛黄、美白、提亮肤色的功效。This application is the first to combine Poria cocos, Tribulus terrestris, Bletilla striata, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni to extract, and the various herbs in the obtained compound Chinese medicine extract complement each other to achieve the effects of anti-glycation, anti-yellowing, whitening and brightening skin color.
在一些实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1-4∶4-10∶8-10∶1-4∶1-4∶1-4。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶ 白芨∶白鲜皮的重量比为1∶4∶10∶10∶1∶4∶4。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶2∶8∶10∶4∶1∶2。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1∶10∶10∶4∶1∶1。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1∶4∶10∶4∶1∶1。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1∶4∶10∶2∶1∶1。在一个具体的实施方式中，本发明的中药提取物中原料茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶2∶4∶8∶4∶1∶2。In some embodiments, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1-4: 4-10: 8-10: 1-4: 1-4: 1-4. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1-4: 4-10: 8-10: 1-4: 1-4: 1-4. The weight ratio of Bletilla striata: Dictamni is 1:4:10:10:1:4:4. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:2:8:10:4:1:2. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:1:10:10:4:1:1. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni is 1:1:4:10:4:1:1. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 1: 4: 10: 2: 1: 1. In a specific embodiment, the weight ratio of the raw materials Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in the Chinese medicine extract of the present invention is 1: 2: 4: 8: 4: 1: 2.
本发明的中药提取物可以作为功效添加剂加入到化妆品中使用，以达到抗糖化、祛黄、美白、提亮肤色的功效。The Chinese medicinal extract of the present invention can be added into cosmetics as an effective additive to achieve the effects of anti-glycation, yellowing, whitening and brightening skin tone.
提取方法Extraction Method
本发明的中药提取物通过溶剂提取法制备。常见提取溶剂包括但不限于：水(例如去离子水)、有机溶剂(例如乙醇)。还有其他的提取方式，包括微波提取、超临界二氧化碳提取、超声波提取、酶提取法等。The Chinese medicine extract of the present invention is prepared by solvent extraction. Common extraction solvents include, but are not limited to, water (e.g., deionized water) and organic solvents (e.g., ethanol). There are other extraction methods, including microwave extraction, supercritical carbon dioxide extraction, ultrasonic extraction, enzyme extraction, etc.
在一些实施方式中，本发明的中药提取物采用水提醇沉进行制备。例如，本发明的中药提取物采用去离子水煮沸提取，然后进行醇沉，获取滤液，得到所需的中药提取物。在一个具体的实施方式中，醇沉过程采用乙醇。在一些实施方式，水提醇沉的提取过程持续1-24小时。在一些实施方式，水提醇沉的提取过程持续12-16小时。In some embodiments, the Chinese medicine extract of the present invention is prepared by water extraction and alcohol precipitation. For example, the Chinese medicine extract of the present invention is extracted by boiling with deionized water, and then precipitated with alcohol to obtain a filtrate to obtain the desired Chinese medicine extract. In a specific embodiment, ethanol is used in the alcohol precipitation process. In some embodiments, the extraction process of water extraction and alcohol precipitation lasts for 1-24 hours. In some embodiments, the extraction process of water extraction and alcohol precipitation lasts for 12-16 hours.
在一些实施方式中，本发明的中药提取物采用醇作为提取溶剂。例如，本发明的中药提取物可以采用乙醇提取。在优选的实施方式中，提取过程在煮沸条件下(例如80±10℃)进行。在优选的实施方式中，可以采用70体积％的乙醇进行提取。在一些实施方式中，醇提取过程持续2-4小时。In some embodiments, the Chinese medicine extract of the present invention uses alcohol as an extraction solvent. For example, the Chinese medicine extract of the present invention can be extracted with ethanol. In a preferred embodiment, the extraction process is carried out under boiling conditions (e.g., 80 ± 10 ° C). In a preferred embodiment, 70% by volume ethanol can be used for extraction. In some embodiments, the alcohol extraction process lasts for 2-4 hours.
中药提取物与多元醇的后处理物Post-treatment products of Chinese herbal medicine extracts and polyols
本发明将中药提取物与多元醇组合形成后处理物。在优选的实施方式 中，中药提取物与多元醇按照1∶10的重量比进行组合。The present invention combines the Chinese herbal medicine extract with a polyol to form a post-processed product. In the method, the Chinese herbal medicine extract and the polyol are combined in a weight ratio of 1:10.
本发明所用术语“多元醇”是指分子中具有2个及以上羟基的水溶性多元醇，包括但不限于：甘油、双甘油、丁二醇、戊二醇、丙二醇、乙基己基甘油、聚乙二醇、山梨糖醇等。多元醇在化妆品中常用作保湿剂，从环境中吸收水分，补充到肌肤中，增加皮肤表面的含水量。多元醇可以单独使用，或者它们可以组合使用。例如，可以将2种或更多种多元醇组合使用。The term "polyol" used in the present invention refers to a water-soluble polyol having two or more hydroxyl groups in the molecule, including but not limited to: glycerol, diglycerol, butylene glycol, pentanediol, propylene glycol, ethylhexylglycerol, polyethylene glycol, sorbitol, etc. Polyols are commonly used as moisturizers in cosmetics, absorbing moisture from the environment, replenishing it into the skin, and increasing the water content of the skin surface. Polyols can be used alone, or they can be used in combination. For example, two or more polyols can be used in combination.
在一些实施方式中，将本发明的中药提取物与重量比为9∶1的戊二醇和丙二醇的混合物进行组合。在一些实施方式中，将本发明的中药提取物与重量比为5∶5的聚乙二醇和辛甘醇的混合物进行组合。In some embodiments, the herbal extract of the present invention is combined with a mixture of pentylene glycol and propylene glycol in a weight ratio of 9: 1. In some embodiments, the herbal extract of the present invention is combined with a mixture of polyethylene glycol and caprylyl glycol in a weight ratio of 5: 5.
从软化细胞膜层和角质层角度看，丁二醇，戊二醇，乙基己基甘油是优选的。因此，在优选的实施方式中，将中药提取物与重量比为9∶1的丁二醇和乙基己基甘油的混合物进行组合。From the perspective of softening the cell membrane layer and the stratum corneum, butylene glycol, pentylene glycol, and ethylhexylglycerol are preferred. Therefore, in a preferred embodiment, the Chinese herbal extract is combined with a mixture of butylene glycol and ethylhexylglycerol in a weight ratio of 9:1.
美白组合物Whitening composition
可以将中药提取物与多元醇组合形成的后处理物与美白成分进一步组合以形成美白组合物。The post-processed product formed by combining the Chinese herbal medicine extract with the polyol can be further combined with a whitening component to form a whitening composition.
维生素C/衍生物是一种安全的美白功效成分，其具有很强的抗氧化性，能改善面部暗沉，同时有效的抑制酪氨酸酶的活性、抑制黑色素的形成，提供根源美白效果。Vitamin C/derivatives are safe whitening ingredients with strong antioxidant properties. They can improve facial dullness, while effectively inhibiting the activity of tyrosinase and the formation of melanin, providing a root whitening effect.
烟酰胺是一种水溶性维生素，其为维生素B族中成员之一，它可以由烟酸在活体内转变而来，具有维生素效应。抗坏血酸葡糖苷(Ascorbic acid 2-glucoside，AA2G)是维生素C的衍生物，同样具有维生素效应。然而，烟酰胺和抗坏血酸葡糖苷的经皮渗透性一直是没有解决的核心问题之一。Nicotinamide is a water-soluble vitamin and a member of the vitamin B family. It can be converted from nicotinic acid in vivo and has a vitamin effect. Ascorbic acid 2-glucoside (AA2G) is a derivative of vitamin C and also has a vitamin effect. However, the transdermal permeability of nicotinamide and ascorbic acid 2-glucoside has always been one of the core issues that have not been resolved.
将活性物抗坏血酸葡糖苷和/或烟酰胺与本发明所述中药提取物与多元醇的后处理物进行组合，可以明显提高皮肤的光泽透明度，使得皮肤“透白”，表层匀净透亮。美白活性成分、维生素C/衍生物、烟酰胺，可以从源头抑制黑色素，搭配的烟酰胺进一步切断黑色素向皮肤表皮细胞的传递，防止色斑，同时更能帮助肌肤内源祛黄，改善暗沉，使产品的美白/透亮功效得到最大程度的发挥。 Combining the active ingredients ascorbyl glucoside and/or niacinamide with the post-processed product of the Chinese herbal extract and polyols of the present invention can significantly improve the gloss and transparency of the skin, making the skin "translucent white" and the surface clean and bright. Whitening active ingredients, vitamin C/derivatives, and niacinamide can inhibit melanin from the source, and the combined niacinamide further cuts off the transmission of melanin to the epidermal cells of the skin to prevent spots, and at the same time can help the skin to remove endogenous yellowing and improve dullness, so that the whitening/brightening effect of the product can be maximized.
本发明提供了包含烟酰胺和/或抗坏血酸葡糖苷的美白组合物。The present invention provides a whitening composition comprising niacinamide and/or ascorbyl glucoside.
在一些实施方式中，本发明的美白组合物包含1-5重量％的烟碱胺。在优选的实施方式中，本发明的美白组合物包含3重量％的烟碱胺。In some embodiments, the whitening composition of the present invention comprises 1-5 wt% nicotinamide. In a preferred embodiment, the whitening composition of the present invention comprises 3 wt% nicotinamide.
在一些实施方式中，本发明的美白组合物包含0.1-2重量％的抗坏血酸葡糖苷。在优选的实施方式中，本发明的美白组合物包含0.1-1重量％的抗坏血酸葡糖苷。In some embodiments, the whitening composition of the present invention comprises 0.1-2 wt% ascorbyl glucoside. In a preferred embodiment, the whitening composition of the present invention comprises 0.1-1 wt% ascorbyl glucoside.
在一些实施方式中，本发明的美白组合物包含10-50重量％的后处理物。在一些实施方式中，本发明的美白组合物包含10-30重量％的后处理物。在一些实施方式中，本发明的美白组合物包含30-50重量％的后处理物。In some embodiments, the whitening composition of the present invention comprises 10-50% by weight of the post-treatment. In some embodiments, the whitening composition of the present invention comprises 10-30% by weight of the post-treatment. In some embodiments, the whitening composition of the present invention comprises 30-50% by weight of the post-treatment.
冻干产品Freeze-dried products
本发明还涉及中药提取物的冻干产品。在一些实施方式中，冻干产品可以是无定形粉末。The present invention also relates to a freeze-dried product of a Chinese herbal medicine extract. In some embodiments, the freeze-dried product may be an amorphous powder.
在一些实施方式中，采用北京博医康实验仪器有限公司的真空冷冻干燥机FD-2型进行冻干。In some embodiments, freeze-drying is performed using a vacuum freeze dryer model FD-2 produced by Beijing Boyikang Laboratory Instrument Co., Ltd.
在一些实施方式中，冷冻干燥设置-80～-40℃，真空度1～30Pa，时间8小时，升华干燥设置-20～+20℃，真空度1～30Pa，时间6小时，含水量控制在0～6％之间，解析干燥设置-10～+20℃，真空度1～30Pa，时间3小时，含水量控制在0～6％之间。In some embodiments, freeze drying is set at -80 to -40°C, vacuum degree 1 to 30Pa, time 8 hours, sublimation drying is set at -20 to +20°C, vacuum degree 1 to 30Pa, time 6 hours, water content is controlled between 0 and 6%, analytical drying is set at -10 to +20°C, vacuum degree 1 to 30Pa, time 3 hours, and water content is controlled between 0 and 6%.
皮肤外用剂Skin topical products
本发明还涉及一种皮肤外用剂，该皮肤外用剂包含本发明的美白组合物或其冻干产品，以及化妆品、皮肤病学或药学上可接受的赋形剂。The present invention also relates to an external skin preparation, which comprises the whitening composition of the present invention or a lyophilized product thereof, and a cosmetically, dermatologically or pharmaceutically acceptable excipient.
在一些优选的实施方式中，以所述皮肤外用剂的总重量计，美白组合物的用量为0.001-50％(w/w)，优选为1-20％(w/w)，更优选为2-10％(w/w)，最优选为3-8％(w/w)。In some preferred embodiments, the amount of the whitening composition is 0.001-50% (w/w), preferably 1-20% (w/w), more preferably 2-10% (w/w), and most preferably 3-8% (w/w), based on the total weight of the external skin preparation.
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。The skin external application 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 may be a basic cosmetic, a facial makeup cosmetic, a body cosmetic, a hair care cosmetic, etc., and there is no particular limitation on its dosage form. It can be reasonably selected according to different purposes.
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。This skin external preparation can be formulated into any suitable product form. Such product forms include, but are not limited to, aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions, hand-pump sprays, sticks, facial masks and wet tissues. This skin external preparation can be conveniently used for preparation or as a cosmetic, dermatological or pharmaceutical topical application product by various methods well known in the art.
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。The skin topical composition of the present invention may include one or more of the following ingredients: antiallergic agents, antimicrobial agents, antioxidants, chelating agents, colorants, depigmenting agents, emollients, emulsifiers, exfoliants, film formers, fragrances, moisturizers, insect repellents, lubricants, pharmaceutically active agents, moisturizers, photostabilizers, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity regulators, vitamins or any combination thereof.
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。The cosmetic, dermatological or pharmaceutically acceptable excipients that can be used for the skin topical composition of the present invention are in the form of an aqueous phase, an oil phase, a gel, a wax-in-water emulsion, an oil-in-water emulsion or an oil-in-water emulsion. The aqueous phase is a mixture of one or more water-soluble or dispersible components, which can be liquid, semi-solid or solid at room temperature (25° C.). The excipient includes or can be in the form of a suspension, dispersion or solution in water or a water-alcohol excipient, which can contain a thickener or a gelling agent. Those skilled in the art can select a suitable product form based on the knowledge mastered by those skilled in the art, the components contained therein.
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。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 a linear or branched lower monohydric alcohol containing 2 to 5 carbon atoms, such as ethanol or propanol; a polyol, such as propylene glycol, sorbitol, glycerol, panthenol or polyethylene glycol, and mixtures thereof.
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。When the composition of the invention is in the form of an emulsion, the composition may also optionally contain a surfactant.
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。The composition may also comprise a film-forming polymer, such as polyurethanes, polyacrylic acid homopolymers or copolymers, polyesters, hydrocarbon-based resins and/or silicone resins. The polymer may be dissolved or dispersed in a cosmetically acceptable vehicle and optionally combined with a plasticizer.
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。 The composition of the present invention may also comprise an oil phase, which contains an oil-soluble or oil-dispersible component that is liquid at room temperature (25° C.) and/or an oily or waxy substance at room temperature, such as wax, semisolid, gum and a mixture thereof. The oil phase may also contain an organic solvent.
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。Suitable oily substances are usually liquid at room temperature and include: hydrocarbon-based oils of animal origin, such as fully hydrogenated squalene; hydrocarbon-based vegetable oils, such as liquid C4-10 fatty acid triglycerides, for example heptanoic acid or caprylic acid triglycerides, or oils, for example sunflower oil, corn oil, soybean oil, grape seed oil, castor oil, avocado oil, caprylic/capric triglycerides, jojoba oil; linear or branched hydrocarbons of mineral or synthetic origin, for example liquid paraffin and its derivatives, vaseline; synthetic esters and ethers, in particular esters of fatty alcohols, for example isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, isostearyl isostearate; hydroxylated esters, for example isostearyl lactate, hydroxy octyl stearate, octyl hydroxystearate, octyldodecyl hydroxystearate, heptanoates, caprylates and caprates of fatty alcohols; polyol esters, such as propylene glycol dicaprylate, neopentyl glycol diheptanoate, diethylene glycol diisononanoate and pentaerythritol esters; fatty alcohols containing C12-26, such as octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleyl alcohol; fluorinated oils and/or fluorinated silicone oils based on partial hydrocarbons, silicone oils, volatile or non-volatile linear or cyclic polymethylsiloxanes that are liquid or semisolid at room temperature, such as cyclopolydimethylsiloxanes and polydimethylsiloxanes, which optionally contain phenyl groups, such as phenyltrimethicone, siloxanes and mixtures thereof.
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。The composition of the present invention may further comprise any components commonly used in the cosmetic field. These components include preservatives, aqueous phase thickeners (extract biopolymers, synthetic polymers) and fat phase thickeners, fragrances, hydrophilic and lipophilic active agents and mixtures thereof.
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。The composition of the present invention may also contain an additional particulate phase, which may be a pigment and/or pearlescent agent and/or filler used in cosmetic compositions.
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。Pigments may be present in the composition, suitable inorganic pigments include titanium, zirconium and cerium oxides as well as zinc oxide, iron oxide and ferric blue; suitable organic pigments include barium, strontium, calcium and aluminium lakes and carbon black.
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。Pearlescent agents may be present in the composition. Suitable pearlescent agents include mica coated with titanium oxide, iron oxide or natural pigments.
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。Fillers may be present in the composition, suitable fillers include talc, silica, zinc stearate, mica, kaolin, nylon powder, polyethylene powder, Teflon, starch, boron nitride, copolymer microspheres, such as silicone resin microspheres.
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。The oil phase of the composition of the present invention may comprise one or more waxes, gums or mixtures thereof. The waxes include hydrocarbon-based waxes, fluoro waxes and/or silicone waxes and may be derived from plant, mineral, animal and/or synthetic sources. Suitable waxes include beeswax, carnauba wax, candelilla wax, paraffin wax, microcrystalline wax, ozokerite wax; synthetic waxes include polyethylene wax, silicone wax containing C16-45. Gums are generally polydimethylsiloxane or sodium carboxymethylcellulose or extracts, and semi-solid substances are generally hydrocarbon-based compounds, such as lanolin and its derivatives.
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。The composition of the present invention can be formulated into any suitable product form. Such product forms include, but are not limited to, aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, pomades, solutions, hand-pump sprays, sticks, facial masks, and wet wipes. The composition of the present invention can be conveniently used to prepare or as a cosmetic, dermatological, or pharmaceutical topical application product by various methods well known in the art.
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。The skin topical composition of the present invention may include one or more of the following ingredients: antiallergic agents, antimicrobial agents, antioxidants, chelating agents, colorants, depigmenting agents, emollients, emulsifiers, exfoliants, film formers, fragrances, moisturizers, insect repellents, lubricants, pharmaceutically active agents, moisturizers, photostabilizers, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity regulators, vitamins or any combination thereof.
具体实施方式Detailed ways
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。The present invention will be further described below in conjunction with specific examples. However, it should be understood that these examples are only used to illustrate the present invention and do not constitute a limitation of the scope of the present invention. The test methods in the following examples that do not specify specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.
以下实施例中采用的药材原材料均购自“安徽亳州京皖中药饮片厂”，来料形态为“中草药饮片”；采用的生物试剂均购自上海家化生物科技有限公司。The medicinal raw materials used in the following examples were all purchased from "Anhui Bozhou Jingwan Chinese Medicine Pieces Factory", and the incoming materials were in the form of "Chinese herbal medicine pieces"; the biological reagents used were all purchased from Shanghai Jahwa Biotechnology Co., Ltd.
以下实施例中采用的实验仪器如下：The experimental instruments used in the following examples are as follows:
1.固定搅拌器(IKA RW20)1. Fixed stirrer (IKA RW20)
2.恒温水浴锅上海一恒科学仪器有限公司HWS 28型2. Constant temperature water bath Shanghai Yiheng Scientific Instrument Co., Ltd. HWS 28
3.称量天平METTLER TOLEDO PL602-S 3. Weighing balance METTLER TOLEDO PL602-S
4.电热恒温CO2培养箱(Thermo，150i)4. Electric constant temperature CO2 incubator (Thermo, 150i)
5.冰箱5. Refrigerator
6.色彩色差计Minolta CR-3006. Minolta CR-300 Colorimeter
7.Waters 2690 HPLC，Waters 2487双波长吸收检测器7. Waters 2690 HPLC, Waters 2487 dual wavelength absorption detector
8.高速万能粉碎机(FW100型)8. High-speed universal pulverizer (FW100 model)
9.中药材提取浓缩罐(TNH型)9. Chinese herbal medicine extraction and concentration tank (TNH type)
10.紫外可见分光光度仪(赛默飞)10. UV-Vis spectrophotometer (Thermo Fisher)
11.真空冷冻干燥机，型号FD-2型，北京博医康实验仪器有限公司11. Vacuum freeze dryer, model FD-2, Beijing Boyikang Laboratory Instrument Co., Ltd.
12.超净工作台(苏州安泰，SW-CJ-IF)12. Clean bench (Suzhou Antai, SW-CJ-IF)
13.酶标仪(BioTek，Epoch)13. Microplate reader (BioTek, Epoch)
14.倒置显微镜(Olympus，CKX41)14. Inverted microscope (Olympus, CKX41)
15.正置显微镜(Olympus，BX53)15. Upright microscope (Olympus, BX53)
实施例1：中药提取物的制备Example 1: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶4∶10∶10∶1∶4∶4，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入体积浓度70％的乙醇，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in a weight ratio of 1:4:10:10:1:4:4, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add 70% volume concentration of ethanol while stirring, let stand for 12 hours, filter, and reduce the pressure to concentrate the filtrate to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例2：中药提取物的制备Example 2: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶8∶10∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合 液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex according to the weight ratio of 1:2:8:10:4:1:2, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid to obtain a Chinese medicine complex extract. Disperse the above extracts in a 1:10 weight ratio of butylene glycol: ethylhexylglycerin mixture Liquid (pre-prepared at a weight ratio of 9:1), stir until evenly mixed and set aside.
实施例3：中药提取物的制备Example 3: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶10∶10∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in a weight ratio of 1:1:10:10:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例4：中药提取物的制备Example 4: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:4:10:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例5：中药提取物的制备Example 5: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶2∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。 Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:4:10:2:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例6：中药提取物的制备Example 6: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶4∶8∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:4:8:4:1:2, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例7：中药提取物的制备Example 7: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶4∶10∶10∶1∶4∶4，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:4:10:10:1:4:4, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例8：中药提取物的制备Example 8: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶8∶10∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:8:10:4:1:2, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例9：中药提取物的制备Example 9: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶10∶10∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇 溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex according to the weight ratio = 1:1:10:10:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol The solution (70% volume concentration) was boiled in an extraction and concentration tank, maintained at 80°C for 2 hours, filtered, the residue was extracted once, filtered again, the two filtrates were combined, and the filtrates were concentrated under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. The above extract was dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
实施例10：中药提取物的制备Example 10: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓：蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:4:10:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例11：中药提取物的制备Example 11: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶2∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:4:10:2:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例12：中药提取物的制备Example 12: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶4∶8∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。 Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:4:8:4:1:2, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例13：中药提取物的制备(对比例)Example 13: Preparation of Chinese herbal medicine extract (Comparative Example)
称取茯苓经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder from Poria cocos and grind it with a high-speed universal grinder, add 12 kg of deionized water and boil it in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue again, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let it stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例14：中药提取物的制备(对比例)Example 14: Preparation of Chinese herbal medicine extract (Comparative Example)
称取蒺藜经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder obtained by grinding Tribulus terrestris with a high-speed universal grinder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once again, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例15：中药提取物的制备(对比例)Example 15: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白蔹经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder obtained by grinding the white mulberry with a high-speed universal grinder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the filter residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例16：中药提取物的制备(对比例)Example 16: Preparation of Chinese herbal medicine extract (Comparative Example)
称取芍药经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将 以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder of peony root and grind it with a high-speed universal grinder. Add 12 kg of deionized water and boil it in an extraction and concentration tank. Keep it at a slight boil for 1 hour, filter it, extract the residue again, filter it again, combine the two filtrates, concentrate it to 1.5 kg, cool it, add ethanol to 70% by volume while stirring, let it stand for 12 hours, filter it, and concentrate the filtrate under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. The above extracts are dispersed into a mixed liquid of butanediol and ethylhexylglycerin (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
实施例17：中药提取物的制备(对比例)Example 17: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白术经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder obtained by grinding Atractylodes macrocephala with a high-speed universal grinder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue again, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例18：中药提取物的制备(对比例)Example 18: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白芨经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder from Bletilla striata and grind it with a high-speed universal grinder, add 12 kg of deionized water and boil it in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue again, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let it stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例19：中药提取物的制备(对比例)Example 19: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白鲜皮经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh the Dictamni cortex and grind it into 1kg of coarse powder by a high-speed universal grinder, add 12kg of deionized water and boil it in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the filter residue once, filter it again, combine the two filtrates, concentrate it to 1.5kg, cool it, add ethanol to 70% ethanol volume concentration while stirring, let it stand for 12 hours, filter it, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extract in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例20：中药提取物的制备(对比例)Example 20: Preparation of Chinese herbal medicine extract (Comparative Example)
称取茯苓经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％ 体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos and grind it into 1 kg of coarse powder using a high-speed universal grinder. Add 10 kg of ethanol solution (70% The extract was boiled in an extraction and concentration tank, maintained at 80°C for 2 hours, filtered, the residue was extracted once, filtered again, the two filtrates were combined, and the filtrates were concentrated under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. The above extract was dispersed in a mixed liquid of butanediol and ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
实施例21：中药提取物的制备(对比例)Example 21: Preparation of Chinese herbal medicine extract (Comparative Example)
称取蒺藜经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of Tribulus terrestris and grind it into a high-speed universal grinder to obtain a coarse powder. Add 10 kg of ethanol solution (70% volume concentration) and boil it in an extraction and concentration tank. Keep the temperature at 80°C for 2 hours, filter, extract the residue again, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例22：中药提取物的制备(对比例)Example 22: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白蔹经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder obtained by grinding the white mulberry with a high-speed universal grinder, add 10 kg of ethanol solution (70% volume concentration) in an extraction and concentration tank, boil, maintain the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例23：中药提取物的制备(对比例)Example 23: Preparation of Chinese herbal medicine extract (Comparative Example)
称取芍药经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder obtained by grinding peony with a high-speed universal grinder, add 10 kg of ethanol solution (70% volume concentration) in an extraction and concentration tank, boil, maintain the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例24：中药提取物的制备(对比例)Example 24: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白术经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣 复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Atractylodes macrocephala and grind it into 1 kg of coarse powder with a high-speed universal grinder. Add 10 kg of ethanol solution (70% volume concentration) and boil it in an extraction and concentration tank. Keep the temperature at 80°C for 2 hours, filter it, and collect the residue. Extract once more, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain the Chinese medicine compound extract. Disperse the above extracts in a mixed liquid of butanediol and ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例25：中药提取物的制备(对比例)Example 25: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白芨经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh 1 kg of coarse powder from Bletilla striata and grind it with a high-speed universal grinder, add 10 kg of ethanol solution (70% volume concentration) and boil it in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue again, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例26：中药提取物的制备(对比例)Example 26: Preparation of Chinese herbal medicine extract (Comparative Example)
称取白鲜皮经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh the Dictamni cortex and grind it into 1kg of coarse powder by a high-speed universal grinder, add 10kg of ethanol solution (70% volume concentration) in an extraction and concentration tank, boil, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine composite extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例27：中药提取物的制备(对比例)Example 27: Preparation of Chinese herbal medicine extract (Comparative Example)
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶0∶10∶10∶1∶4∶4，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex = 1:0:10:10:1:4:4 by weight, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例28：中药提取物的制备Example 28: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶ 0∶10∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh out Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex according to the weight ratio = 1:2: 0:10:4:1:2, after mixing, pulverize with high-speed universal pulverizer to obtain 1kg of coarse powder, add 12kg of deionized water and boil in an extraction concentration tank, keep slightly boiling for 1 hour, filter, extract the residue again, filter again, combine the two filtrates, concentrate to 1.5kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. The above extract is dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
实施例29：中药提取物的制备Example 29: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶10∶0∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:10:0:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例30：中药提取物的制备Example 30: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶0∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex = 1:1:4:10:0:1:1 by weight, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例31：中药提取物的制备Example 31: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶4∶10∶2∶0∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤， 合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex according to the weight ratio = 1:1:4:10:2:0:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it at a slight boil for 1 hour, filter, extract the residue again, and filter again. Combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例32：中药提取物的制备Example 32: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶4∶8∶4∶1∶0，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex in a weight ratio of 1:2:4:8:4:1:0, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例33：中药提取物的制备Example 33: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝0∶2∶4∶8∶4∶1∶0，混合后经高速万能粉碎机粉碎得粗粉1kg，加12kg去离子水于提取浓缩罐中煮沸，保持微沸1小时，过滤，滤渣复提一次，再过滤，合并两次滤液，浓缩至1.5kg，冷却，边搅拌边加入乙醇至乙醇体积浓度70％，静置12小时，过滤，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex = 0: 2: 4: 8: 4: 1: 0 by weight, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 12 kg of deionized water and boil in an extraction and concentration tank, keep it slightly boiling for 1 hour, filter, extract the residue once, filter again, combine the two filtrates, concentrate to 1.5 kg, cool, add ethanol to 70% ethanol volume concentration while stirring, let stand for 12 hours, filter, and concentrate the filtrate under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9: 1) at a weight ratio of 1: 10, stir until uniformly mixed, and set aside.
实施例34：中药提取物的制备Example 34: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶0∶10∶10∶1∶4∶4，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶ 乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex = 1:0:10:10:1:4:4 by weight, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in butanediol according to a weight ratio of 1:10: Ethylhexylglycerin mixed liquid (pre-prepared in a weight ratio of 9:1), stir until uniformly mixed, and set aside.
实施例35：中药提取物的制备Example 35: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶0∶10∶4∶1∶2，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Ampelopsis radix: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:0:10:4:1:2, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例36：中药提取物的制备Example 36: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶1∶10∶0∶4∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:1:10:0:4:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例37：中药提取物的制备Example 37: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶0∶4∶10∶0∶1∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:0:4:10:0:1:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例38：中药提取物的制备Example 38: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶0∶4∶10∶2∶0∶1，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶 液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex according to the weight ratio of 1:0:4:10:2:0:1, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol to dissolve. The extract (70% volume concentration) was boiled in an extraction and concentration tank, maintained at 80°C for 2 hours, filtered, the residue was extracted once, filtered again, the two filtrates were combined, and the filtrates were concentrated under reduced pressure to a dry solid state to obtain the Chinese medicine complex extract. The above extract was dispersed in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stirred until uniformly mixed, and set aside.
实施例39：中药提取物的制备Example 39: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝1∶2∶0∶8∶4∶1∶0，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 1:2:0:8:4:1:0, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared in a weight ratio of 9:1) in a weight ratio of 1:10, stir until uniformly mixed, and set aside.
实施例40：中药提取物的制备Example 40: Preparation of Chinese herbal medicine extract
按重量比例称取茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮＝0∶2∶0∶8∶4∶1∶0，混合后经高速万能粉碎机粉碎得粗粉1kg，加10kg乙醇溶液(70％体积浓度)于提取浓缩罐中煮沸，保持温度80℃持续2小时，过滤，滤渣复提一次，再过滤，合并两次滤液，滤液减压浓缩至干燥固态，即得中药复合物提取物。将以上提取物按照重量比1∶10分散到丁二醇∶乙基己基甘油混合液体(重量比9∶1预制)中，搅拌至均匀混合，备用。Weigh Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Cortex Dictamni in a weight ratio of 0:2:0:8:4:1:0, mix and grind with a high-speed universal grinder to obtain 1 kg of coarse powder, add 10 kg of ethanol solution (70% volume concentration) and boil in an extraction and concentration tank, keep the temperature at 80°C for 2 hours, filter, extract the residue once, filter again, combine the two filtrates, and concentrate the filtrates under reduced pressure to a dry solid state to obtain a Chinese medicine complex extract. Disperse the above extracts in a mixed liquid of butanediol: ethylhexylglycerol (pre-prepared at a weight ratio of 9:1) at a weight ratio of 1:10, stir until uniformly mixed, and set aside.
测试例1：活性物检测Test Example 1: Active substance detection
取实施例1～40中药复合物提取物分别检测其中活性物含量。The extracts of the Chinese medicinal compound of Examples 1 to 40 were taken to detect the content of active ingredients therein.
药物活性成分的化学结构是药物经皮渗透的关键。脂溶性的药物易于透过角质层和皮肤屏障、细胞膜，但在活性表皮中由于水分含量相对较高从而扩散较慢。而水溶性成分药物通过角质层细胞膜及皮肤屏障的速度较慢，但在活性表皮中扩散却较快。一般在选用功能性药物活性成分中，注重成分的分子结构，尽可能选择用油/水分配适中的药物成分，或者水溶性和脂溶性成分配合使用，往往能得到较好的效果。The chemical structure of active drug ingredients is the key to drug transdermal penetration. Fat-soluble drugs easily penetrate the stratum corneum, skin barrier, and cell membrane, but diffuse slowly in the active epidermis due to the relatively high water content. Water-soluble drugs penetrate the stratum corneum cell membrane and skin barrier slowly, but diffuse quickly in the active epidermis. Generally, when selecting active ingredients for functional drugs, attention is paid to the molecular structure of the ingredients, and drug ingredients with a moderate oil/water distribution are selected as much as possible, or water-soluble and fat-soluble ingredients are used together, which often achieves better results.
1，2，3，4，6-O-没食子酰葡萄糖(PGG)是一种多酚类化合物，由5个没 食子酸与1个葡萄糖通过酯键结合而成，相对分子量940，具有较好的亲水和亲油性，具有较强的生理活性，如抗多种肿瘤、抗氧化、抗白血病、抗过敏、降血糖等功能，存在于多种中药材中。1,2,3,4,6-O-Galloylglucose (PGG) is a polyphenolic compound composed of 5 It is composed of ester acid and one glucose through an ester bond, with a relative molecular weight of 940. It has good hydrophilicity and lipophilicity and strong physiological activity, such as anti-tumor, anti-oxidation, anti-leukemia, anti-allergy, and hypoglycemic functions. It exists in many Chinese medicinal materials.
高效液相色谱法测定：High performance liquid chromatography determination:
色谱条件与***适用性试验采用C18通用型Eclipse XDB-C18(4.6x250mm，5μm)色谱柱；以乙腈-0.1％稀磷酸(25∶75)为流动相；梯度洗脱后，检测波长为230nm；柱温为35℃；流速为0.8mL/min；进样量为10μL。理论板数按照1，2，3，4，6-O-没食子酰葡萄糖(PGG)峰值计算应不低于200000。Chromatographic conditions and system suitability tests were performed using a C18 universal Eclipse XDB-C18 (4.6x250mm, 5μm) column; acetonitrile-0.1% dilute phosphoric acid (25:75) as the mobile phase; after gradient elution, the detection wavelength was 230nm; the column temperature was 35℃; the flow rate was 0.8mL/min; the injection volume was 10μL. The theoretical plate number calculated according to the 1,2,3,4,6-O-galloylglucose (PGG) peak should be no less than 200,000.
对照品溶液的制备，精密称取干燥至恒重的PGG对照品，加入甲醇制成每1mL含0.2mg的混合溶液，摇匀即得。Preparation of reference solution: accurately weigh the PGG reference substance dried to constant weight, add methanol to make a mixed solution containing 0.2 mg per 1 mL, and shake well.
待测样品制备，取实施例1～3中药提取物和实施例4～6酶解反应粗产物各1mL，精密称定，置5mL量瓶中，加甲醇稀释至刻度，摇匀即得。Preparation of the sample to be tested: 1 mL of each of the Chinese medicinal extracts of Examples 1 to 3 and the crude product of the enzymatic hydrolysis reaction of Examples 4 to 6 were accurately weighed, placed in a 5 mL volumetric flask, diluted to the mark with methanol, and shaken to obtain the sample.
测定，分别精密吸取对照品溶液和待测样品溶液各10μL，注入高效液相色谱仪，记录HPLC图谱，得到图1。For determination, 10 μL of the reference solution and the sample solution to be tested were accurately pipetted and injected into a high performance liquid chromatograph, and the HPLC spectrum was recorded to obtain Figure 1.
测定实施例1～40含量结果如下表1所示。The results of measuring the contents of Examples 1 to 40 are shown in Table 1 below.
表1：实施例1～40中药提取物中PGG含量

Table 1: PGG content in Chinese herbal extracts of Examples 1 to 40

结果显示，经过不同的提取工艺，实施例1～6中草药复合提取物获得了较高的PGG获得量，尤其以实施例2为最，达到了0.4006mg/ml，相比较实施例6高出了96％。对于实施例7～12而言，醇提的工艺即便是同样的中草药的配伍比例，在活性成分PGG的含量上，整体偏低，尤其是同样配比的实施例8，相较于实施例2来说，含量约低13.7％；同样地，在实施例1～6的水提醇沉工艺中，即便是同样的比例和配伍，整体的PGG含量高于实施例7～12醇提工艺。The results show that after different extraction processes, the Chinese herbal compound extracts of Examples 1 to 6 obtained a higher amount of PGG, especially Example 2, which reached 0.4006 mg/ml, 96% higher than Example 6. For Examples 7 to 12, the alcohol extraction process, even with the same compatibility ratio of Chinese herbal medicines, has a lower content of active ingredient PGG as a whole, especially Example 8 with the same ratio, which is about 13.7% lower than Example 2; similarly, in the water extraction and alcohol precipitation process of Examples 1 to 6, even with the same ratio and compatibility, the overall PGG content is higher than that of the alcohol extraction process of Examples 7 to 12.
对比不同配比的提取物，尤其是删减7味中草药材中的1味或多味的情况下，水提醇沉或者醇提工艺制备获得的PGG含量普遍低于7味药材共同存在的情况，如实施例14，甚至出现了未检出PGG的情况。对比实施例2与实施例13～40中获得的PGG含量，基本在2～100倍之间；总体而言，通过不同比例配伍获得的7种不同的中药材，不同的配伍和比例之间有较大的活性物含量的差异，而且对于不同的提取工艺，也存在着活性物含量的较大差异。Comparing the extracts with different proportions, especially when one or more of the seven Chinese herbal medicines are deleted, the PGG content obtained by water extraction and alcohol precipitation or alcohol extraction process is generally lower than that of the seven herbs co-existing, such as Example 14, where PGG was not detected. Comparing the PGG content obtained in Example 2 with that obtained in Examples 13 to 40, it is basically between 2 and 100 times; in general, the seven different Chinese herbal medicines obtained by combining in different proportions have large differences in active substance content between different combinations and proportions, and there are also large differences in active substance content for different extraction processes.
实施例41～112：提取物与美白成分的复配Examples 41-112: Compounding of extracts and whitening ingredients
按照表2的重量比例称取实施例2样品、烟酰胺(VB3)、抗坏血酸葡糖苷(AA2G)和水，搅拌均匀得到100克溶液，备用。 According to the weight ratio in Table 2, the sample of Example 2, nicotinamide (VB3), ascorbyl glucoside (AA2G) and water were weighed and stirred to obtain 100 g of solution for later use.
表2：实施例按照重量比配制溶液


Table 2: Example solutions prepared according to weight ratio


测试例2：基于黑素模型的美白功效测试Test Example 2: Whitening efficacy test based on melanin model
此次测试所用3D黑素皮肤模型(批号：MS220304，广 东博溪生物科技有限公司)，准备6孔板，每孔添加3.7mL M-TA培养液，将气液面培养第3天，即模型接收当天(Day0)的模型转移至标记好的6孔板中；每个试验分组需要6个模型(用于表观色度、L*b*值及黑素含量的测定)，将所有放有模型的6孔板转移至CO2培养箱中培养(37℃、5％CO2)。采用UVB(50mJ/cm2)作为刺激条件，表观色度的测量将比色卡置于单反相机正下方，用镊子将单个模型放置于比色卡色圈内，进行拍照。单反相机参数设置为手动拍照模式，焦距调至5.8mm，孔径设置为f/8，光圈调至F22，快门速度设置为1/80s，ISO设置为1600。L*值和b*值测试，对表观色度检测结束后的模型，进行L*值、b*值检测。具体检测操作如下：将模型置于平整坚硬的白色平面上，角质层朝上放置，按照色差仪使用说明，将色差仪检测孔垂直对准模型表面进行检测，每个模型重复读数三次，并记录数据，取平均值作为单个模型的L*值、b*值读数。检测后的模型放入干净的EP管中，用于黑素含量测定。黑素含量测试1)将模型置于1.5mL EP管中，标号，每管加入1mL PBS缓冲液，涡旋振荡仪震荡3min，低温高速离心机2000r/min，离心10min，弃上清；2)向步骤(1)中EP管中依次加入200μL蒸馏水，500μL无水乙醇和500μL***，充分混匀后，室温静置20min，3000r/min离心The 3D melanin skin model used in this test ( Batch number: MS220304, Guangdong Dongboxi Biotechnology Co., Ltd.) prepared a 6-well plate, added 3.7 mL of M-TA culture medium to each well, and transferred the model on the third day of gas-liquid surface culture, that is, the day the model was received (Day 0), to the marked 6-well plate; each test group required 6 models (for the determination of apparent chromaticity, L*b* value and melanin content), and all 6-well plates with models were transferred to a CO 2 incubator for culture (37°C, 5% CO 2 ). UVB (50 mJ/cm 2 ) was used as the stimulus condition. For the measurement of apparent chromaticity, the colorimetric card was placed directly below the SLR camera, and a single model was placed in the color circle of the colorimetric card with tweezers to take a photo. The SLR camera parameters were set to manual photography mode, the focal length was adjusted to 5.8 mm, the aperture was set to f/8, the aperture was adjusted to F22, the shutter speed was set to 1/80s, and the ISO was set to 1600. L* value and b* value test, the model after the apparent chromaticity test was completed, the L* value and b* value test were performed. The specific detection operation is as follows: Place the model on a flat and hard white surface with the stratum corneum facing upwards. According to the instructions for use of the colorimeter, align the detection hole of the colorimeter vertically with the surface of the model for detection. Repeat the reading for each model three times and record the data. Take the average value as the L* value and b* value reading of the single model. The tested model is placed in a clean EP tube for melanin content determination. Melanin content test 1) Place the model in a 1.5mL EP tube, label it, add 1mL PBS buffer to each tube, vortex on a vortex oscillator for 3 minutes, centrifuge at 2000r/min at a low temperature and high speed centrifuge for 10 minutes, and discard the supernatant; 2) Add 200μL of distilled water, 500μL of anhydrous ethanol and 500μL of ether to the EP tube in step (1) in sequence, mix thoroughly, let stand at room temperature for 20 minutes, and centrifuge at 3000r/min.
5min，弃上清；3)加入1mL含10％DMSO的1mol/L NaOH水溶液，80℃水浴中加热40min，使黑素颗粒完全溶解；4)热孵育结束后，吸取200μL上清液至标号清楚的96孔板对应孔中，在405nm读取OD值，每个模型在96孔板上测试两个平行。5min, discard the supernatant; 3) add 1mL of 1mol/L NaOH aqueous solution containing 10% DMSO and heat in an 80℃ water bath for 40min to completely dissolve the melanin particles; 4) After the heat incubation, aspirate 200μL of supernatant into the corresponding wells of a clearly labeled 96-well plate, read the OD value at 405nm, and test two parallels for each model on the 96-well plate.
数据统计分析应用GraphPad Prism作图，结果表示为Mean±SD。各组间比较采用t-test统计分析。统计分析均为双尾。P＜0.05认为具有显著差异，P＜0.01认为具有极显著差异。GraphPad Prism was used for statistical analysis, and the results were expressed as Mean ± SD. The t-test was used for statistical analysis between the groups. All statistical analyses were two-tailed. P < 0.05 was considered to be significantly different, and P < 0.01 was considered to be extremely significantly different.
表3：实施例41～112基于黑素模型的美白功效(黑素含量)结果



Table 3: Whitening efficacy (melanin content) results of Examples 41 to 112 based on the melanin model



皮肤“透”“光”“白”的核心影响因素包括1)皮肤中黑色素的含量；2)皮肤肌底发生的(内源性)黯黄；3)氧化因子造成的肌肤炎症；4)皮肤屏障功能及含水量；根据对中国女性皮肤暗黄、暗沉等影响因素的研究，随着年龄的增加，中国女性面部亮度显著降低，黄度显著增加，黯黄是中国女性区别于高加索女性、墨西哥女性的特征性变化。皮肤“暗”和“黄”最主要的影响因素分别是黑色素的合成和蛋白质羰基化等，以上两种反应皆可由氧化应激诱发。正常生理条件下，机体具备完善的抗氧化防御机制 (酶抗氧化***和非酶抗氧化***)。如今随着自然环境恶化，现代社会竞争加剧，都市人群伴随各种不良的生活方式(熬夜、饮食不节、缺乏运动或过量运动)，身体处于亚健康状态，无法提供足够的抗氧化物质，进而引起氧化应激反应。The core factors affecting skin "transparency", "brightness" and "whiteness" include 1) the content of melanin in the skin; 2) (endogenous) dark yellowing of the skin base; 3) skin inflammation caused by oxidative factors; 4) skin barrier function and water content; According to research on factors affecting the dark yellowing and dullness of Chinese women's skin, with increasing age, the facial brightness of Chinese women decreases significantly, and the yellowness increases significantly. Dark yellowing is a characteristic change that distinguishes Chinese women from Caucasian women and Mexican women. The main factors affecting "dark" and "yellow" skin are the synthesis of melanin and protein carbonylation, respectively. Both reactions can be induced by oxidative stress. Under normal physiological conditions, the body has a complete antioxidant defense mechanism. (Enzyme antioxidant system and non-enzyme antioxidant system). Nowadays, with the deterioration of the natural environment and the intensification of competition in modern society, urban people have various unhealthy lifestyles (staying up late, unhealthy diet, lack of exercise or excessive exercise), and their bodies are in a sub-healthy state and cannot provide enough antioxidants, which in turn causes oxidative stress.
维生素C/衍生物是一种安全的美白功效成分，其具有很强的抗氧化性，能改善面部暗沉，同时有效的抑制酪氨酸酶的活性、抑制黑色素的形成，提供根源美白效果。Vitamin C/derivatives are safe whitening ingredients with strong antioxidant properties. They can improve facial dullness, while effectively inhibiting the activity of tyrosinase and the formation of melanin, providing a root whitening effect.
烟酰胺是一种水溶性维生素，其为维生素B族中成员之一，它可以由烟酸在活体内转变而来，二者均具有维生素效应。然而烟酸易引发皮肤瘙痒、发红过敏等一系列问题，所以本发明中选用99％以上高纯度烟酰胺，最大程度避免了烟酸的混入。烟酰胺能够有效阻止黑色素的传递，从而带来美白、淡斑效果。在文献中，报道了维生素C联合烟酰胺使用，在治疗黄褐斑上取得较为满意的结果，另外，二者可引起内源性抗氧化剂NAD(P)H水平升高，具有帮助肌肤深层抗糖化作用，从而内源性调节皮肤黯黄现象。但对于烟酰胺配合AA2G的经皮渗透性一直是没有解决的核心问题之一。Nicotinamide is a water-soluble vitamin, which is a member of the vitamin B family. It can be converted from nicotinic acid in vivo, and both have vitamin effects. However, nicotinic acid is prone to cause a series of problems such as skin itching, redness and allergies, so the present invention uses more than 99% high-purity nicotinamide to avoid the mixing of nicotinic acid to the greatest extent. Nicotinamide can effectively prevent the transmission of melanin, thereby bringing whitening and spot-lightening effects. In the literature, it is reported that the use of vitamin C combined with nicotinamide has achieved relatively satisfactory results in the treatment of chloasma. In addition, the two can cause an increase in the level of endogenous antioxidant NAD(P)H, which has the effect of helping the skin to resist glycation in the deep layer, thereby endogenously regulating the skin's dark yellowing phenomenon. However, the transdermal permeability of niacinamide combined with AA2G has always been one of the core issues that have not been resolved.
中草药化妆品的核心功效的发挥首先需要研究的就是活性成分的透皮吸收和利用的问题。当皮肤角质层中含水量低于10％后，角朊细胞排列状态更加紧密，减少了皮肤有效透入面积和物质透皮的空间，从而降低了药物的透皮吸收程度和效率。在这种皮肤环境下，即使加大药物用量，效果并无太大改善，所以功能性化妆品，首先要做的是把皮肤的含水量恢复到正常水平或处于水润状态，角质层含水10％或以上，表皮中其他各层10％～47％，当表皮中含水量达到10％～50％时，使得紧密的角朊细胞形成多孔和饱满状态，增加了皮肤的有效面积和接触的横截面，药物的透皮吸收速度大大提高，在皮肤保湿的环境下药物会发挥更好的作用。现代生物学研究表明：茯苓、蒺藜、白蔹都具有明确的抑制络氨酸酶活性作用，白术、白芨(及)具有明确的抗氧化作用，白芍具有一定的促进血液循环、促进新陈代谢、匀净透亮的作用。The first thing that needs to be studied to realize the core efficacy of Chinese herbal cosmetics is the transdermal absorption and utilization of active ingredients. When the water content in the stratum corneum of the skin is lower than 10%, the keratinocytes are arranged more tightly, which reduces the effective penetration area of the skin and the space for substances to penetrate the skin, thereby reducing the degree and efficiency of transdermal absorption of drugs. In this skin environment, even if the dosage of the drug is increased, the effect is not much improved. Therefore, the first thing to do for functional cosmetics is to restore the water content of the skin to a normal level or a moist state. The stratum corneum contains 10% or more water, and the other layers of the epidermis contain 10% to 47%. When the water content in the epidermis reaches 10% to 50%, the compact keratinocytes become porous and plump, increasing the effective area of the skin and the contact cross-section, and the transdermal absorption rate of the drug is greatly improved. In the environment of moisturizing the skin, the drug will play a better role. Modern biological research shows that Poria, Tribulus terrestris and Bletilla striata all have a clear effect of inhibiting tyrosinase activity, Atractylodes macrocephala and Bletilla striata (and) have a clear antioxidant effect, and White Peony Root has a certain effect of promoting blood circulation, promoting metabolism, and making the skin even and bright.
本发明首次将卓效保湿成分小分子多元醇(丁二醇)和乙基己基甘油润泽肌肤，增强肌肤屏障，增加肌肤含水量的功效。丁二醇是化妆品中经 典的功效性保湿成分，丁二醇为小分子成分，分子量仅90g/mol，其具有很好的肌肤保湿与渗透性。采用乙基己基甘油与丁二醇结合的“双生”增“透”技术，可以帮助肌肤达到双重渗透且明显增加滋润度的效果，能使活性物的渗“透”效果明显增加。双效增润，快速抓水、锁水，滢亮透白肌。将活性物抗坏血酸葡糖苷、烟酰胺和中草药美白复方进行组合使用，可以明显提高皮肤的光泽透明度，是皮肤的“透白“精华，表层匀净透亮。美白中草药活性成分、维生素C/衍生物、烟酰胺，可以从源头抑制黑色素，抗氧化，搭配烟酰胺进一步切断黑色素向皮肤表皮细胞的传递，防止色斑，同时更能帮助肌肤内源祛黄，改善暗沉，使产品的美白/透亮功效得到最大程度的发挥。This invention is the first to combine the highly effective moisturizing ingredients, small molecule polyols (butylene glycol) and ethylhexylglycerin, to moisturize the skin, strengthen the skin barrier, and increase the moisture content of the skin. Butylene glycol is a A classic functional moisturizing ingredient, butylene glycol is a small molecule with a molecular weight of only 90g/mol. It has good skin moisturizing and permeability. The "twin""permeation" technology combining ethylhexylglycerin and butylene glycol can help the skin achieve double penetration and significantly increase the moisturizing effect, which can significantly increase the penetration effect of active ingredients. Double-effect moisturizing, fast water retention, water lock, bright and white skin. The combination of active ingredients ascorbyl glucoside, niacinamide and Chinese herbal whitening compound can significantly improve the gloss and transparency of the skin. It is the "translucent white" essence of the skin, with a uniform and translucent surface. Whitening Chinese herbal active ingredients, vitamin C/derivatives, and niacinamide can inhibit melanin from the source and resist oxidation. Niacinamide can further cut off the transmission of melanin to the epidermal cells of the skin to prevent spots. At the same time, it can help the skin to remove yellowness endogenously and improve dullness, so that the whitening/translucent effect of the product can be maximized.
对比了相同浓度下的中草药复合提取物搭配不同比例的美白成分后，抑制黑色素的效果差异。The differences in melanin inhibition effects were compared when the same concentration of Chinese herbal compound extracts were combined with different proportions of whitening ingredients.
从实施例41～112的结果来看(见表3)，实施例与组合物绝大部分具有抑制黑色素的效果，从相对改善率维度来看，优选的7种中草药组合改善在12％以上，这与相同实施例提取物中PGG的含量也是有正相关性的。从实施例2，4，8，10为优选的中草药提取物的后处理产物，通过与特定的美白成分组合复配，较大幅度地提升了实施例提取物在抑制黑素含量方面的改善率，比如实施例43提升到了50.67％，实施例44提升到了46.27％，实施例54提升到了42.41％，实施例62提升到了50％，平均的提升比例超过了30％，说明采用选定的两种物质进行复配组合能较大程度提高中草药复合物提取物的抑制黑素含量的功效。From the results of Examples 41 to 112 (see Table 3), most of the examples and compositions have the effect of inhibiting melanin. From the perspective of relative improvement rate, the preferred combination of 7 Chinese herbal medicines improves by more than 12%, which is also positively correlated with the content of PGG in the extracts of the same examples. Examples 2, 4, 8, and 10 are post-processed products of preferred Chinese herbal extracts. By compounding with specific whitening ingredients, the improvement rate of the example extracts in inhibiting melanin content is greatly improved, such as Example 43 increased to 50.67%, Example 44 increased to 46.27%, Example 54 increased to 42.41%, and Example 62 increased to 50%. The average improvement ratio exceeds 30%, indicating that the use of the selected two substances for compounding can greatly improve the efficacy of the Chinese herbal compound extract in inhibiting melanin content.
对比两种美白成分同比例下的自身的抑制黑素含量能力，基本来说抑制黑素含量功效不高，说明中草药复合物的活性物在抑制黑素含量功效的发挥具有较大的促进作用。Comparing the melanin-inhibiting capabilities of the two whitening ingredients at the same ratio, it is generally found that the melanin-inhibiting effects are not high, indicating that the active ingredients of the Chinese herbal complex play a greater role in promoting the effects of melanin inhibition.
与此同时，与实施例2，4，8，10提取物后处理产物与前述较高含量的PGG有一定的相关性，多元醇的加入可以极大地提升中草药活性成分被细胞的利用率是可能的工作机制。At the same time, there is a certain correlation between the post-processing products of the extracts of Examples 2, 4, 8, and 10 and the aforementioned higher content of PGG. The addition of polyols can greatly improve the utilization rate of the active ingredients of Chinese herbal medicines by cells, which is a possible working mechanism.
从图2可以更加直观地看到抑制黑素含量的表观色度，实施例43对标NC和PC明显改善。 From Figure 2, we can more intuitively see the apparent chromaticity of the suppression of melanin content, and Example 43 is significantly improved compared with NC and PC.
测试例3：基于激光拉曼共聚焦方法的渗透性能测试Test Example 3: Permeability test based on laser Raman confocal method
采用配备532nm(He-Ne激光)激光源、半导体冷却的CCD探测器(1024×800像素)和25μm共焦针孔的共焦拉曼显微镜***(Thermo，DXR2Xi型)；激光束采用50x长焦物镜(NA 0.50BD)用于获取样品参数。测量前使用由硅板(520.5cm-1)产生的拉曼散射射线进行标准单点校准。所有光谱均在50～3400cm-1范围内采集。通过X-Y扫描获得每个点的拉曼光谱。扫描样品的激光功率为3.5mW，光谱各点的积分时间为0.05sec。所有拉曼光谱数据都经过预处理(宇宙射线去除、背景去除、平滑和降噪)。拉曼图像是通过使用X-Z拉曼深度成像得到的。实验从单光谱采集开始，在获得单光谱后，首先对单光谱进行预处理，并对光谱质量进行评估，以探查实验条件。随后，采用逐点扫描方式进行深度扫描成像，采集光谱数据步距为2μm，扫描面积为8μm×100μm(4×50像素)，光谱积分时间为每个像素点为0.05秒。A confocal Raman microscope system (Thermo, DXR2Xi model) equipped with a 532nm (He-Ne laser) laser source, a semiconductor-cooled CCD detector (1024×800 pixels) and a 25μm confocal pinhole was used; the laser beam was used with a 50x telephoto objective (NA 0.50BD) to obtain sample parameters. Before the measurement, a standard single-point calibration was performed using Raman scattered rays generated by a silicon plate (520.5cm -1 ). All spectra were collected in the range of 50 to 3400cm -1 . The Raman spectrum of each point was obtained by XY scanning. The laser power for scanning the sample was 3.5mW, and the integration time for each point of the spectrum was 0.05sec. All Raman spectral data were preprocessed (cosmic ray removal, background removal, smoothing and noise reduction). Raman images were obtained by using XZ Raman deep imaging. The experiment started with single spectrum acquisition. After obtaining a single spectrum, the single spectrum was first preprocessed and the spectral quality was evaluated to explore the experimental conditions. Subsequently, a point-by-point scanning method was used for depth scanning imaging. The spectral data was collected with a step size of 2 μm, a scanning area of 8 μm × 100 μm (4 × 50 pixels), and a spectral integration time of 0.05 seconds for each pixel.
所有光谱均由Thermo Fisher SCIENTIFIC的OMSNIC记录，用于数据处理。使用R(i386 4.0.3)分析数据。拉曼光谱经基线校正，S-G二阶平滑，统计分析前归一化；使用K均值聚类分析拉曼成像剖面中的光谱变化。K-means是一种基于光谱数据的相似性对光谱数据进行分类的数据处理方法。将每个光谱看作是二维空间中的一个点，因此光谱之间的相似性可以通过相似系数和距离在数学上定义。首先设置簇数k，将待聚类的光谱分为k类，通过迭代最小化每类所有光谱与簇中心的距离和，即使相似光谱之间的相似度为最高。K均值聚类是从k个簇的随机簇分布开始，然后根据它们与簇的平均谱的最小距离迭代求解，这项工作一直进行到达成稳定的安排为止，构建彩色图以更清晰地观察皮肤组织随深度的差异。该算法的优点是计算速度快、过程简单、适用性广。为了得到可靠的结果，必须对收集到的拉曼光谱进行预处理，对原始光谱进行包括去除宇宙射线，去除基线背景以及平滑降噪的处理。在实验过程中，为了确保实验数据的准确性必须要对拉曼光谱进行预处理。因为在测量过程中，会存在荧光背景，宇宙射线以及高斯噪声或者泊松噪声的干扰，这些会影响拉曼信息的采集和 获取。为了获取未被干扰的数据，必须要排除这些影响因素，所以要进行基线校正。基线校正后对光谱进行平滑处理，采用Savitzky-Golay滤波(基于最小二乘的卷积拟合算法)对光谱机械能平滑处理。All spectra were recorded by OMSNIC of Thermo Fisher SCIENTIFIC for data processing. Data were analyzed using R (i386 4.0.3). Raman spectra were baseline corrected, SG second-order smoothed, and normalized before statistical analysis; K-means clustering was used to analyze spectral changes in Raman imaging profiles. K-means is a data processing method that classifies spectral data based on the similarity of spectral data. Each spectrum is regarded as a point in a two-dimensional space, so the similarity between spectra can be mathematically defined by similarity coefficients and distances. First, the number of clusters k is set, and the spectra to be clustered are divided into k categories. The sum of the distances of all spectra in each category to the cluster center is minimized iteratively, that is, the similarity between similar spectra is the highest. K-means clustering starts with a random cluster distribution of k clusters, and then iteratively solves them according to their minimum distance to the average spectrum of the cluster. This work is carried out until a stable arrangement is reached, and a color map is constructed to more clearly observe the differences in skin tissue with depth. The advantages of this algorithm are fast calculation speed, simple process, and wide applicability. In order to obtain reliable results, the collected Raman spectra must be preprocessed, including removing cosmic rays, removing baseline background, and smoothing and reducing noise. During the experiment, in order to ensure the accuracy of the experimental data, the Raman spectra must be preprocessed. Because during the measurement process, there will be interference from fluorescence background, cosmic rays, and Gaussian noise or Poisson noise, which will affect the collection and In order to obtain undisturbed data, these influencing factors must be eliminated, so baseline correction is required. After baseline correction, the spectrum is smoothed, and the Savitzky-Golay filter (convolution fitting algorithm based on least squares) is used to smooth the spectral mechanical energy.
实验测试所用的皮肤组织(六周，雄性乳猪腹部，购买自重庆梅盛商贸有限公司)。购买获得的乳猪腹部皮肤冷冻保存在-25℃的冰箱中，实验前将冷冻的皮肤样品放入装有PBS(pH＝7.4，5ml)的培养皿中解冻，皮肤表皮朝上暴露在空气中并且真皮部分浸入到PBS缓冲液中。皮肤样品的大小保持在1.5×1.5cm2，在整个实验测量过程中，皮肤样品的下端始终与PBS缓冲液接触。在皮肤样品完全解冻后，需要将其置于PBS溶液中2h以达到皮肤表面不再溢出油脂和水分，实验室室温保持在25±2℃，空气湿度保持在45±5％。整个实验过程中皮肤样品始终保持下端润湿。取用2.5μL以上实施例样品滴涂在每个皮肤样品的中心部位，随即开始单光谱测量和拉曼成像。单个样品的共聚焦显微成像和偏振拉曼成像时间控制在3h以内，以确保样品不会因为湿度温度的变化导致其屏障功能发生改变。The skin tissue used in the experimental test (six weeks, male suckling pig abdomen, purchased from Chongqing Meisheng Trading Co., Ltd.). The purchased suckling pig abdomen skin was frozen and stored in a refrigerator at -25°C. Before the experiment, the frozen skin sample was thawed in a culture dish filled with PBS (pH=7.4, 5ml), with the skin epidermis facing up and exposed to the air and the dermis part immersed in the PBS buffer. The size of the skin sample was maintained at 1.5×1.5cm 2. During the entire experimental measurement process, the lower end of the skin sample was always in contact with the PBS buffer. After the skin sample was completely thawed, it was necessary to place it in the PBS solution for 2h to achieve that the skin surface no longer overflowed with oil and moisture. The laboratory room temperature was maintained at 25±2°C and the air humidity was maintained at 45±5%. The lower end of the skin sample was always moistened during the entire experiment. 2.5μL of the above example sample was dripped on the center of each skin sample, and then single spectrum measurement and Raman imaging were started. The confocal microscopy imaging and polarized Raman imaging time of a single sample was controlled within 3h to ensure that the sample would not change its barrier function due to changes in humidity and temperature.
对实施例43进行了激光拉曼共聚焦渗透性能方面的测试评价，对比非本发明专利优选的美白成分的溶液(即相同浓度的VB3)，结果如图3所示。图3为拉曼光谱的直观呈现，加注了皮肤深度的标尺(最左侧)和程度标尺的最大和最小方向，从标尺可知黄颜色表示渗透最大，蓝颜色表示渗透最小。在皮肤的横切面上，是从皮肤表面到皮肤深层，即0-100μm。从左图可以看到，120分钟后，物质基本可以渗透到60-100μm深处；对比右侧图片可以看到，120分钟后，大部分的物质仍然停留在0-20μm的皮肤表层。The laser Raman confocal penetration performance of Example 43 was tested and evaluated, and compared with the solution of the whitening ingredient preferred by the patent of the present invention (i.e., VB3 of the same concentration), the results are shown in Figure 3. Figure 3 is a direct presentation of the Raman spectrum, with the scale of skin depth (leftmost) and the maximum and minimum directions of the degree scale added. It can be seen from the scale that yellow indicates maximum penetration and blue indicates minimum penetration. On the cross-section of the skin, it is from the skin surface to the deep layer of the skin, i.e., 0-100μm. As can be seen from the left picture, after 120 minutes, the substance can basically penetrate to a depth of 60-100μm; compared with the picture on the right, it can be seen that after 120 minutes, most of the substance still remains in the skin surface layer of 0-20μm.
从渗透的结果数据来看，实施例43的渗透效率显著提升，即在相同的时间内，实施例43中美白成分的渗透效率更高，渗透的更加深入。From the penetration result data, it can be seen that the penetration efficiency of Example 43 is significantly improved, that is, within the same period of time, the penetration efficiency of the whitening component in Example 43 is higher and the penetration is deeper.
中草药复方添加剂里面的主要功效物质为黄酮、多酚、多糖等，具体的组分的分布和含量多数依赖于萃取方法和手段，而且因为多数物质不易保存，储存不当易发生氧化、分解、挥发、变质等问题而导致功效物质的损失。制备工艺后期也可以采用先进的冻干技术，使得提取物中的活性成分能够较好的保留，可以在更大程度上保留活性成分的原汁原味，特别是 热敏性的活性成分，另外，因在真空无氧下操作，因此，一些易氧化的活性成分(如油脂类)也可以得到保护。在真空和低温下操作，微生物的生长和酶作用受到抑制，常温下能长久储存，而且不需添加任何防腐剂，减少微生物的侵蚀，延长产品的保质期。The main active ingredients in Chinese herbal compound additives are flavonoids, polyphenols, polysaccharides, etc. The distribution and content of specific components mostly depend on the extraction method and means. Moreover, since most substances are not easy to preserve, improper storage can easily lead to oxidation, decomposition, volatilization, deterioration and other problems, resulting in the loss of active ingredients. Advanced freeze-drying technology can also be used in the later stage of the preparation process to better retain the active ingredients in the extract, and to retain the original flavor of the active ingredients to a greater extent, especially Heat-sensitive active ingredients. In addition, some easily oxidized active ingredients (such as oils) can also be protected because of the vacuum and oxygen-free operation. When operated under vacuum and low temperature, the growth of microorganisms and enzyme action are inhibited. It can be stored for a long time at room temperature without adding any preservatives, reducing microbial erosion and extending the shelf life of the product.
综上所述，按照中医智慧思想配伍的实施例获得的提取物经过特定美白组合配比后得到的实施例41～112具有更好的抑制黑素生成的美白效果。In summary, the extracts obtained in the examples according to the wisdom of traditional Chinese medicine are combined and matched in specific whitening combinations to obtain examples 41 to 112, which have better whitening effects in inhibiting melanin production.
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0.001％-50％(w/w)。优选的重量百分比为1％-20％(w/w)。更优选的重量百分比为2％-10％(w/w)。最优选的重量百分比为3％-8％(w/w)。The skin external preparation is preferably a cosmetic composition, such as a toner, an essence, a cream, etc. The weight percentage of the composite extract in the skin external preparation is 0.001%-50% (w/w). The preferred weight percentage is 1%-20% (w/w). The more preferred weight percentage is 2%-10% (w/w). The most preferred weight percentage is 3%-8% (w/w).
以下是中药提取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。The following are examples of specific applications of Chinese herbal extracts in skin topical preparations, and the formulations and preparation methods of these dosage forms. In the following tables, "-" means no addition.
应用例1：面霜的制备

Application Example 1: Preparation of facial cream

应用例2：乳液的制备
Application Example 2: Preparation of Emulsion
应用例3：啫喱的制备

Application Example 3: Preparation of Gel

应用例4：化妆水的制备
Application Example 4: Preparation of lotion
应用例5：精华液的制备

Application Example 5: Preparation of Essence

应用例6：面膜的制备

Application Example 6: Preparation of facial mask

应用例7：眼霜的制备
Application Example 7: Preparation of Eye Cream
应用例8：沐浴露的制备

Application Example 8: Preparation of Shower Gel

应用例9：洗面奶的制备

Application Example 9: Preparation of facial cleanser

本发明中的实施例82～121也可以作为低温冷冻干燥产品单独使用。Embodiments 82 to 121 of the present invention can also be used alone as low-temperature freeze-dried products.
利用本发明的组合物制得的上述化妆品取得与市售的产品相当或更好的使用效果。The cosmetics prepared by using the composition of the present invention have the same or better use effects as the commercially available products.
本发明通过上述实施例来说明本发明的详细方法，但本发明并不局限于上述详细方法，即不意味着本发明必须依赖上述详细方法才能实施。所属技术领域的技术人员应该明了，对本发明的任何改进，对本发明产品各原料的等效替换及辅助成分的添加、具体方式的选择等，均落在本发明的保护范围和公开范围之内。 The present invention illustrates the detailed method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed method, that is, it does not mean that the present invention must rely on the above-mentioned detailed method to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims (10)

  1. 一种促渗增效的美白组合物，包含：A whitening composition for promoting penetration and enhancing efficacy, comprising:
    美白成分；Whitening ingredients;
    中药提取物；和Chinese herbal medicine extracts; and
    多元醇，Polyol,
    其中，所述中药提取物通过以下原料制备得到：茯苓、蒺藜、白蔹、芍药、白术、白芨和白鲜皮，其中，茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1-4∶4-10∶8-10∶1-4∶1-4∶1-4，The Chinese medicine extract is prepared from the following raw materials: Poria, Tribulus, Bletilla striata, Paeonia lactiflora, Atractylodes macrocephala, Bletilla striata and Dictamni cortex, wherein the weight ratio of Poria: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex is 1:1-4:4-10:8-10:1-4:1-4:1-4,
    其中，所述多元醇是重量比为9∶1的丁二醇和乙基己基甘油的混合物。The polyol is a mixture of butanediol and ethylhexylglycerol in a weight ratio of 9:1.
  2. 如权利要求1所述的组合物，所述美白成分选自：烟酰胺、抗坏血酸葡糖苷或它们的组合。The composition according to claim 1, wherein the whitening ingredient is selected from: niacinamide, ascorbyl glucoside or a combination thereof.
  3. 如权利要求1所述的组合物，其中，茯苓∶蒺藜∶白蔹∶芍药∶白术∶白芨∶白鲜皮的重量比为1∶1-2∶4-8∶8-10∶1-4∶1-4∶1-2。The composition according to claim 1, wherein the weight ratio of Poria cocos: Tribulus terrestris: Bletilla striata: Paeonia lactiflora: Atractylodes macrocephala: Bletilla striata: Dictamni cortex is 1:1-2:4-8:8-10:1-4:1-4:1-2.
  4. 如权利要求1所述的组合物，其中，所述中药提取物通过溶剂提取制备得到。The composition according to claim 1, wherein the Chinese herbal medicine extract is prepared by solvent extraction.
  5. 如权利要求4所述的组合物，其中，所述溶剂提取采用水提醇沉方法。The composition as claimed in claim 4, wherein the solvent extraction adopts a water extraction and alcohol precipitation method.
  6. 如权利要求1所述的组合物，其中，所述中药提取物与多元醇的重量比为1∶10。The composition according to claim 1, wherein the weight ratio of the Chinese herbal medicine extract to the polyol is 1:10.
  7. 如权利要求1所述的组合物，其中，所述组合物包含10-50重量％的中药提取物。 The composition according to claim 1, wherein the composition comprises 10-50% by weight of the Chinese herbal medicine extract.
  8. 如权利要求1-6中任一项所述的美白组合物的冻干产品。A freeze-dried product of the whitening composition according to any one of claims 1 to 6.
  9. 如权利要求1-7中任一项所述的美白组合物或如权利要求8所述的冻干产品在皮肤美白中的应用。Use of the whitening composition according to any one of claims 1 to 7 or the freeze-dried product according to claim 8 in skin whitening.
  10. 一种皮肤外用剂，所述皮肤外用剂包含如权利要求1-7中任一项所述的美白组合物或如权利要求9所述的冻干产品。 A skin external preparation comprising the whitening composition according to any one of claims 1 to 7 or the freeze-dried product according to claim 9.
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