WO2024012387A1 - 包含青蒿提取物和水溶性成分的组合物及其应用 - Google Patents

包含青蒿提取物和水溶性成分的组合物及其应用 Download PDF

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WO2024012387A1
WO2024012387A1 PCT/CN2023/106482 CN2023106482W WO2024012387A1 WO 2024012387 A1 WO2024012387 A1 WO 2024012387A1 CN 2023106482 W CN2023106482 W CN 2023106482W WO 2024012387 A1 WO2024012387 A1 WO 2024012387A1
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extract
vinegar
water
artemisia annua
soluble component
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PCT/CN2023/106482
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English (en)
French (fr)
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孙懿
陈默
赵亚
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 WO2024012387A1 publication Critical patent/WO2024012387A1/zh

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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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/82—Preparation or application process involves sonication or ultrasonication
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/85—Products or compounds obtained by fermentation, e.g. yoghurt, beer, wine

Definitions

  • the present invention belongs to the field of phytochemistry, and specifically relates to a composition comprising an Artemisia annua extract and a water-soluble component and its application in external skin preparations or cosmetics.
  • Allergic reactions can be divided into types I, II, III, and IV according to their mechanisms, and hyaluronidase is a participant in type I allergic reactions and has a strong correlation with inflammation and allergy.
  • Hyaluronidase is a specific cleavage enzyme of hyaluronic acid, and hyaluronic acid displays a variety of physiological functions of traditional Chinese medicine in the body, such as moisturizing and promoting wound healing. According to research reports, some anti-allergic and anti-inflammatory drugs strongly inhibit hyaluronidase activity. Therefore, inhibition of hyaluronidase activity is used as an indicator to study anti-inflammatory effects.
  • flavonoids with hyaluronidase inhibitory activity have been screened from natural products, such as luteolin, kaempferol, and quercetin. Vitamins, etc., and studies have shown that flavonoids that can inhibit hyaluronidase activity also have anti-inflammatory effects. Based on this, we considered that since flavonoids have certain properties, whether some Chinese herbal medicines containing water-soluble components with anti-inflammatory effects also have the effect of inhibiting hyaluronidase activity.
  • Artemisia annua is the whole plant of Artemisia annua L. in the Asteraceae family. Bitter and cold in nature. Returns to the liver, gallbladder, and kidney meridians. It has the effect of clearing away heat, relieving heat and cutting off malaria.
  • Artemisia annua contains the anti-malarial component artemisinin, which can directly kill malaria parasites.
  • Artemisia annua extract has antibacterial and insecticidal, antipyretic and anti-inflammatory, and immune-regulating effects. It also has five kinds of flavonoids with antioxidant activity. Ingredients, including quercetin, etc.
  • White bark is the root bark of Dictamnus dasycarpus Turcz. of the Rutaceae family. Bitter and cold in nature. Returns to the spleen and stomach meridians. It has the effects of clearing heat, drying dampness, dispelling wind and detoxifying. Modern pharmacological experiments have proven that white fresh bark has antibacterial, anti-inflammatory, anti-insect, anti-allergic, hemostatic, antioxidant and other activities.
  • Vinegar brine extract is made by selecting high-quality glutinous rice, crushing it, cooking it, liquefying it, saccharifying it, adding yeast/koji for fermentation, and finally filtering it.
  • the present invention unexpectedly found that the compounding of Artemisia annua extract and water-soluble components (for example, white fresh bark extract and vinegar brine extract) has excellent hyaluronidase inhibitory effect. Therefore, a composition containing artemisia annua extract and water-soluble ingredients can be added to external skin preparations as a compound functional additive to assist in relieving itching, eczema, etc.
  • water-soluble components for example, white fresh bark extract and vinegar brine extract
  • the present invention provides the application of a composition comprising an Artemisia annua extract and a water-soluble component in skin anti-allergy, anti-inflammation and/or anti-irritation, wherein the water-soluble component is selected from the group consisting of White Fresh Peel Extract and Vinegar. Halogen extract.
  • the Artemisia annua extract is prepared by ultrasonic extraction. In a preferred embodiment, the Artemisia annua extract is extracted using water as a solvent.
  • the acetohalogen extract is prepared by the following method:
  • the white fresh peel extract is prepared using an ultrasonic extraction method.
  • the water-soluble component is a white fresh bark extract
  • the weight ratio of the Artemisia annua extract and the white fresh bark extract is 1:4 to 4:1.
  • the water-soluble component is a vinegar-halogen extract
  • the weight ratio of the Artemisia annua extract to the vinegar-halogen extract is 2:1 to 60:1.
  • the anti-inflammatory, anti-allergic and/or anti-irritant effects are achieved by inhibiting hyaluronidase; or used to assist in relieving itching and/or eczema problems.
  • the present invention provides the use of a composition comprising an Artemisia annua extract and a water-soluble component in the preparation of a skin external preparation with skin anti-allergic, anti-inflammatory and/or anti-irritant effects, wherein the water
  • the soluble ingredients are selected from white fresh peel extract and vinegar brine extract.
  • the external skin agent is selected from the group consisting of: cream, lotion, gel, lotion, essence, facial mask, eye cream, aerosol cleansing foam, spray, shower gel, and facial cleanser.
  • Figure 1 shows the results of the positive control hyaluronidase inhibition experiment.
  • Figure 2 shows the results of the hyaluronidase inhibition experiment of Example 2.
  • Figure 3 shows the results of the hyaluronidase inhibition experiment of Example 4.
  • Figure 4 shows the results of the hyaluronidase inhibition experiment of Example 5.
  • Figure 5 shows the results of the hyaluronidase inhibition experiment of Example 6.
  • Figure 6 shows the results of the hyaluronidase inhibition experiment of Example 7.
  • Figure 7 shows the results of the hyaluronidase inhibition experiment of Example 8.
  • Figure 8 shows the results of the hyaluronidase inhibition experiment of Example 9.
  • Figure 9 shows the results of the hyaluronidase inhibition experiment of Example 10.
  • Figure 10 shows the results of the hyaluronidase inhibition experiment of Example 11.
  • the object of the present invention is to provide a composition containing Artemisia annua extract and water-soluble components.
  • the combination of Artemisia annua extract and water-soluble ingredients has a better effect of inhibiting hyaluronidase. Therefore, the composition containing Artemisia annua extract and water-soluble ingredients can be added to skin care products as a compound functional additive to help relieve itching, eczema, etc.
  • Artemisia annua L. is the whole plant of Artemisia annua L. in the Asteraceae family. Bitter and cold in nature. Returns to the liver, gallbladder, and kidney meridians. It has the effect of clearing away heat, relieving heat and cutting off malaria.
  • Artemisia annua contains the anti-malarial ingredient artemisinin, which can directly kill malaria parasites.
  • Artemisia annua extract has antibacterial and insecticidal, antipyretic and anti-inflammatory, and immune-regulating effects. It also has five types of antioxidant activity. Flavonoids, including quercetin, etc.
  • an ultrasonic extraction method is used to extract the Artemisia annua extract.
  • the characteristics of ultrasonic extraction include: 1. Shortening the extraction time, each ultrasound only takes 20min-30min, and conventional extraction is basically 1h-1.5h; 2. Extraction at room temperature does not destroy heat-sensitive components; 3. Direct cell wall breaking and extraction of active ingredients More complete.
  • the process parameters of ultrasonic extraction are as follows: extraction twice, 20 minutes each time, ultrasonic for 3 seconds, and gap of 3 seconds.
  • the extraction solvent is water (eg, deionized water).
  • the extraction process includes an alcohol precipitation step. For example, 95% ethanol is used to achieve alcohol precipitation.
  • the extraction process includes a filtering step. In some embodiments, the extraction process includes a centrifugation step. In some embodiments, the extraction process also includes a concentration step. For example, concentrate to a solid content of 5-20% by weight. In a specific embodiment, the solid content is concentrated to 10.94% by weight.
  • the present invention unexpectedly found that the combination of Artemisia annua extract and water-soluble ingredients (such as white fresh bark extract and vinegar brine extract) has a better synergistic effect on skin anti-sensitivity, anti-inflammatory and/or anti-irritation. Therefore, Artemisia annua extract can be used in combination with water-soluble ingredients to achieve anti-allergic, anti-inflammatory and/or anti-irritant effects on the skin.
  • water-soluble ingredients such as white fresh bark extract and vinegar brine extract
  • the water-soluble ingredient is Alba bark extract.
  • the white peel extract is prepared using an ultrasonic extraction method. For example, it can be prepared using the TGCXN-2B equipment of Beijing Hongxianglong Biotechnology Co., Ltd.
  • the white peel extract is extracted using ethanol (eg, 70-90% ethanol). In a preferred embodiment, 80% ethanol is used for extraction.
  • the preparation of the white peel extract further includes the step of centrifugal filtration.
  • the preparation of the white peel extract further includes a concentration step.
  • the present invention provides a composition comprising an Artemisia annua extract and a White Fresh Peel Extract, wherein the weight ratio of the Artemisia annua extract to the White Fresh Peel extract is 1:4 to 4:1.
  • the weight ratio of the Artemisia annua extract and the White Fresh Bark Extract is 1:2 to 2:1.
  • the weight ratio of the Artemisia annua extract and the White Fresh Bark Extract is 1:1 to 2:1.
  • the water-soluble ingredient is a vinegar brine extract.
  • the vinegar brine is provided by Jiangsu Hengshun Group Co., Ltd.
  • the following method is used to prepare the vinegar brine extract:
  • the resin used in step (d) is selected from the following: any one of non-polar macroporous resin, weakly polar macroporous resin, and polar macroporous resin.
  • the non-polar macroporous resin is D101 resin
  • the weakly polar macroporous resin is AB-8 resin
  • the polar macroporous resin is DM301 resin.
  • step (d) uses water or ethanol for elution.
  • step (d) uses 50-70 volume% ethanol for elution.
  • the vinegar brine extract is prepared according to the method described in Example 5 of the applicant's related patent application 202111158651.X.
  • take 100g of vinegar halogen dilute it with 2-10 times of deionized water
  • add 100g of AB-8 resin perform static adsorption at room temperature, separate the resin by filtration, and elute with deionized water and 50% Elute with ethanol, collect 50% of the eluate, concentrate, and dry to obtain 2.05g of vinegar-halogen extract for later use.
  • the present invention provides a composition comprising an Artemisia annua extract and a vinegar-halogen extract, wherein the weight ratio of the Artemisia annua extract to the vinegar-halogen extract is 2:1 to 60:1. In a preferred embodiment, the weight ratio of the Artemisia annua extract and the vinegar-halogen extract is 10:1 to 60:1. In a preferred embodiment, the weight ratio of the Artemisia annua extract and the vinegar-halogen extract is 50:1 to 60:1.
  • composition comprising artemisia annua extract and water-soluble components of the present invention can be used as a compound functional additive Used in topical preparations for skin.
  • the external skin agent is selected from: facial cleanser, lotion, lotion, cream, gel, and facial mask. Different dosages are added according to different types of preparations.
  • an external skin preparation which includes a composition of an Artemisia annua extract, a water-soluble component, and an excipient acceptable in the field of cosmetics.
  • the external agent for skin is a general term for all ingredients commonly used on the outside of the skin, and may be, for example, a cosmetic composition or a pharmaceutical composition.
  • the cosmetic composition may include basic cosmetics, facial makeup cosmetics, body cosmetics, hair care cosmetics, etc. There are no special restrictions on the dosage form and can be selected appropriately according to different purposes.
  • the cosmetic composition also contains different cosmetically acceptable media or matrix excipients depending on the dosage form and purpose.
  • Dermal topicals contain dermatologically acceptable carriers or vehicles (eg, lotions, creams, ointments, cleansers, etc.). Those of ordinary skill in the art can select a carrier capable of dissolving or dispersing these components at the concentrations described above based on common knowledge in the art. When a carrier is used, it should not cause inactivation of the Artemisia annua extract or water-soluble ingredients and should not cause any adverse effects on the skin when used.
  • dermatologically acceptable carriers or vehicles eg, lotions, creams, ointments, cleansers, etc.
  • the skin external preparation of the present invention may be in the form of a topical application product, which can be externally applied to the skin, and can be prepared by those ordinary techniques known in the art.
  • the carrier may take various practical forms, such as creams, dressings, gels, lotions, ointments or liquids, which comprise the composition for application and cleansing, and they may be incorporated into, for example, dry or A wet applicator, hydrogel matrix, or adhesive (or non-adhesive) patch material carrier.
  • the carrier is a gel or moisturizing lotion, or an application in dry or wet form.
  • Typical carriers include emulsions containing water and/or alcohol and an emollient, such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives, Fatty acids, or fatty acid esters or alcohols or alcohol ethers, lanolin and its derivatives, polyols or esters, wax esters, sterols, phospholipids, etc., generally emulsifiers (nonionic, cationic or anionic), Although some emollients have emulsifying properties of their own. Additionally, these same components may be formulated into creams, gels, or creams, using different ratios of their components and/or by incorporating thickening agents such as gums or other forms of hydrocolloids. Solid stick.
  • an emollient such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives,
  • the skin external preparation of the present invention may contain additional components commonly found in skin care compositions, such as emollients, skin conditioners, emulsifiers, preservatives, antioxidants, fragrances, chelating agents, etc., as long as they are compatible with the skin.
  • additional components commonly found in skin care compositions, such as emollients, skin conditioners, emulsifiers, preservatives, antioxidants, fragrances, chelating agents, etc., as long as they are compatible with the skin.
  • the other components of the topical preparation are physically and chemically compatible.
  • one or more preservatives may be used. Suitable preservatives include p-hydroxyacetophenone, C1-C4 alkyl parabens and phenoxyethanol.
  • the preservative is present in an amount of from about 0.5 to about 2% by weight, preferably from about 0.5 to 1% by weight, based on the total weight of the composition.
  • one or more antioxidants may be used. Suitable antioxidants include butylated hydroxytoluene (BHT), ascorbyl palmitate (BHA), butylated hydroxyanisole, phenyl-alpha-naphthylamine, hydroquinone, propyl gallate, nordihydroguaiaretic acid , vitamin E or derivatives of vitamin E, vitamin C and its derivatives, calcium pantothenate, green tea extract and mixed polyphenols, and mixtures of the above mentioned substances.
  • BHT butylated hydroxytoluene
  • BHA ascorbyl palmitate
  • butylated hydroxyanisole phenyl-alpha-naphthylamine
  • hydroquinone propyl gallate
  • nordihydroguaiaretic acid a antioxidant that is used in an amount ranging from about 0.02 to 0.5% by weight, more most preferably from about 0.002 to 0.1% by weight, based on the total weight of the composition.
  • one or more emollients may be used that act as a lubricant to reduce flaking by their ability to remain on the skin surface or in the stratum corneum, Improves the appearance of skin.
  • Typical emollients include fatty esters, fatty alcohols, mineral oils, polyethersiloxane copolymers, and the like.
  • emollients include, without limitation, polypropylene glycol ("PPG")-15 octadecyl ether, PPG-10 cetyl ether, Steareth-10, Oleth-8, PPG-4 dodecane Ether, vitamin E acetate, lanolin, cetyl alcohol, cetearyl ethyl hexanoate, cetostearyl alcohol, glyceryl stearate, octyl hydroxystearate, dimethylpolysiloxane alkanes, and their combinations. Cetyl alcohol, cetearyl ethylhexanoate, cetearyl alcohol, glycerol stearate and combinations thereof are preferred.
  • the emollient may be present in an amount ranging from about 0.1 to about 30%, preferably from about 1 to about 30% by weight, based on the total weight of the composition.
  • one or more humectants may be used.
  • Moisturizers are also called humectants, which help to increase the effectiveness of emollient, reduce flaking, stimulate the removal of flaky skin and improve skin feel.
  • Polyols can be used as humectants, including but not limited to, glycerin, polyalkylene glycols, alkylene polyols and their derivatives, including butylene glycol, propylene glycol, dipropylene glycol, polyglycerol, polyethylene glycol Alcohols and their derivatives, sorbitol, hydroxypropyl sorbitol, hexanediol, 1,3-dibutyl Diol, 1,2,6-hexanetriol, ethoxylated glycerin, propoxylated glycerin, and combinations thereof.
  • the humectant is present in an amount from about 0.1 to about 20% by weight, preferably from about 1 to about 15% by weight, based on the total weight of the composition.
  • one or more emulsifiers may be used.
  • Emulsifiers can be used within an effective stabilizing amount.
  • the emulsifier is used in an amount from about 1.0 to about 10.0% by weight, more preferably from about 3.0 to about 6.0% by weight, based on the total weight of the composition.
  • Any emulsifier compatible with the components of the composition may be used.
  • Suitable emulsifiers include stearic acid, cetyl alcohol, glyceryl stearate, lecithin, stearyl alcohol, Steareth-2, Steareth-20, acrylic/C10-30 alkanol acrylate cross-links Polymers, and their combinations.
  • one or more pH adjusters may be used.
  • Useful pH adjusters in the skin external preparations of the present invention include tromethamine.
  • the pH adjuster is present in an amount of from about 0.1 to about 2% by weight, preferably from about 0.1 to about 1% by weight, based on the total weight of the composition.
  • the skin external preparation includes acrylic/C10-30 alkanol acrylate crosspolymer, glycerin, p-hydroxyacetophenone, glyceryl stearate and lecithin, /stearyl alcohol, cetearyl ethylhexanoate, tromethamine or combinations thereof.
  • the dosage of the composition of Artemisia annua extract and water-soluble ingredients in the external skin preparation is 0.001%-0.2% (w/w), and the preferred weight percentage is 0.007%-0.1% (w /w), the more preferred weight percentage is 0.007%-0.08% (w/w), and the most preferred weight percentage is 0.007%-0.056% (w/w).
  • the vinegar-halogen extract was prepared according to Example 5 of Chinese patent application CN 202111158651.X (Glutinous rice fermentation extract and its anti-aging application). Specifically, take 100g of vinegar brine, dilute it with 2-10 times of deionized water, add 100g of AB-8 resin, perform static adsorption at room temperature, separate the resin by filtration, and elute with deionized water and 50% ethanol respectively. Collect 50% of the eluate, concentrate and dry to obtain 2.05g of the vinegar-halogen extract, add deionized water to dissolve, and prepare a solution with a solid content of 1% for later use.
  • Example 1 Mix the extract of Example 1 and the extract of Example 5 according to a weight ratio of 1:5 and set aside for later use.
  • potassium tetraborate (national medicine reagent, analytical grade) and use 250ml of water to prepare a 0.4mol/L potassium borate solution for later use.
  • Example 2-11 Take the prepared extract or solution of Example 2-11, dilute it with buffer, conduct the test according to the method in Table 1, measure the absorbance value at 585 nm, and finally calculate its IC 50 .
  • T is the sample
  • T0 is the sample control
  • C is the blank
  • C0 is the blank control
  • IC50 ⁇ 10 mg/ml is excellent, IC50 ⁇ 30 mg/ml is good, IC50 ⁇ 50 mg/ml is average, and IC50 ⁇ 50 mg/ml has basically no application value.
  • Example 6 when the compound ratio of Artemisia annua extract and White fresh bark extract is 1:1, the IC 50 concentration is less than the concentration of a single drug, which is a preferred implementation.
  • Example 6 when the compound ratio of Artemisia annua extract and White fresh bark extract is 1:1, the IC 50 concentration is less than the concentration of a single drug, which is a preferred implementation.
  • Example 11 the compounding ratio of Artemisia annua extract and vinegar-halogen extract is 5:1, and the IC 50 concentration is less than the concentration of a single drug; in Example 9, the compounding ratio of Artemisia annua extract and vinegar-halogen extract is 1:1. 1.
  • the IC 50 concentration is similar to the concentration in Example 2, so Example 11 is preferred, and Example 9 is second preferred.
  • the preparations of Examples 6-11 can be used in the preparation of external preparations for skin.
  • the skin external preparation is preferably a cosmetic composition, such as lotion, essence, cream, etc.
  • the preparation is used externally on the skin
  • the weight percentage in the agent is 0.026%-1.5% (w/w).
  • the preferred weight percentage is 0.026%-0.96% (w/w).
  • a more preferred weight percentage is 0.052%-0.74% (w/w).
  • the most preferred weight percentage is 0.1%-0.48% (w/w).

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Abstract

一种包含青蒿提取物和水溶性成分的组合物在皮肤抗敏、抗炎和/或抗刺激中的应用，以及在制备具有皮肤抗敏、抗炎和/或抗刺激作用的皮肤外用剂中的应用。其中，所述水溶性成分选自白鲜皮提取物和醋卤提取物。

Description

包含青蒿提取物和水溶性成分的组合物及其应用 技术领域
本发明属于植物化学领域，具体涉及包含青蒿提取物和水溶性成分的组合物及其在皮肤外用剂或化妆品中的应用。
背景技术
过敏是由于外源物质进入人体，机体的免疫系统将此类物质识别为异物，致使免疫系统紊乱，引起过敏、炎症等症状。过敏反应根据其机理可分为I、II、III、IV型，而透明质酸酶是I型过敏反应的参与者，与炎症、过敏有强相关性。
透明质酸酶是透明质酸的特异性裂解酶，而透明质酸在机体内显示出多种中药的生理功能，如润肤、促进伤口愈合等。根据研究报道，一些抗敏、抗炎药物有强抑制透明质酸酶活性，因此，抑制透明质酸酶活性作为研究抗炎作用的指标。
为了寻找透明质酸酶的抑制剂，研究者做了大量的工作，目前已知从天然产物中筛选出很多具有抑制透明质酸酶活性的黄酮类化合物，如木樨草素、山奈酚、槲皮素等，而研究表明能够抑制透明质酸酶活性的黄酮类化合物同时也具有抗炎作用。基于此，我们考虑既然黄酮类化合物具有一定特性，那是否有一些含有水溶性成分的具有抗炎作用的中草药也有抑制透明质酸酶活性的功效。
青蒿，为菊科黄花蒿Artemisia annua L.的全草。性苦、寒。归肝、胆、肾经。有清虚热，解暑截疟的作用。青蒿含有抗疟成分青蒿素，可直接杀灭疟原虫，现代研究表明青蒿提取物具有抑菌杀虫、解热抗炎、调节免疫的作用，同时还具有5种抗氧化活性的黄酮类成分，包括槲皮素等。
白鲜皮，为芸香科白鲜Dictamnus dasycarpus Turcz.的根皮。性苦、寒。归脾、胃经。具有清热燥湿，祛风解毒的功效。现代药理实验证明白鲜皮具有抗菌、抗炎、抗虫、抗过敏、止血、抗氧化等多种活性。
醋卤提取物，选择优质糯米粉碎、蒸煮，经液化、糖化后加入酵母/曲麦进行发酵等一系列步骤，最终过滤而成。
本发明意外地发现，将青蒿提取物和水溶性成分(例如，白鲜皮提取物和醋卤提取物)复配，具有优异的抑制透明质酸酶的作用。因此，包含青蒿提取物和水溶性成分的组合物可以作为复配型功效添加剂加入到皮肤外用剂中，以辅助止痒、湿疹问题等。
发明内容
一方面，本发明提供了包含青蒿提取物和水溶性成分的组合物在皮肤抗敏、抗炎和/或抗刺激中的应用，其中，所述水溶性成分选自白鲜皮提取物和醋卤提取物。
在优选的实施方式中，所述青蒿提取物采用超声提取法制备。在优选的实施方式中，所述青蒿提取物采用水作为溶剂提取。
在优选的实施方式中，所述醋卤提取物通过以下方法制备得到：
(a)将糯米粉碎，蒸煮，经糖化后加入酵母菌和麦曲进行酒醪发酵，得到酒醪；
(b)加入麦麸和稻壳，搅拌均匀，接入固态种子醅和复合微生物菌种进行醋醅固态分层发酵，得到醋醅；
(c)取醋醅底部自然渗出的醋卤，得到醋卤；
(d)醋卤经树脂分离洗脱，得到醋卤提取物。
在优选的实施方式中，所述白鲜皮提取物采用超声提取法制备。
在优选的实施方式中，所述水溶性成分是白鲜皮提取物，青蒿提取物与白鲜皮提取物的重量比为1∶4至4∶1。
在优选的实施方式中，所述水溶性成分是醋卤提取物，青蒿提取物与醋卤提取物的重量比为2∶1至60∶1。
在优选的实施方式中，所述抗炎、抗敏和/或抗刺激作用通过抑制透明质酸酶实现；或者用于辅助止痒和/或湿疹问题。
另一方面，本发明提供了包含青蒿提取物和水溶性成分的组合物在制备具有皮肤抗敏、抗炎和/或抗刺激作用的皮肤外用剂中的应用，其中，所述水 溶性成分选自白鲜皮提取物和醋卤提取物。
在优选的实施方式中，所述皮肤外用剂选自：面霜、乳液、啫喱、化妆水、精华液、面膜、眼霜、气雾洁面泡、喷雾、沐浴露、洗面奶。
附图简要说明
图1显示了阳性对照透明质酸酶抑制实验的结果。
图2显示了实施例2透明质酸酶抑制实验的结果。
图3显示了实施例4透明质酸酶抑制实验的结果。
图4显示了实施例5透明质酸酶抑制实验的结果。
图5显示了实施例6透明质酸酶抑制实验的结果。
图6显示了实施例7透明质酸酶抑制实验的结果。
图7显示了实施例8透明质酸酶抑制实验的结果。
图8显示了实施例9透明质酸酶抑制实验的结果。
图9显示了实施例10透明质酸酶抑制实验的结果。
图10显示了实施例11透明质酸酶抑制实验的结果。
具体实施方式
本发明目的在于提供一种包含青蒿提取物和水溶性成分的组合物。具体地，将青蒿提取物与水溶性成分组合后，具有更优的抑制透明质酸酶的作用。因此，包含青蒿提取物和水溶性成分的组合物可作为复配型功效添加剂加入到护肤品中使用，以辅助止痒、湿疹问题等。
为了提供更简明的描述，本文给出的一些数量表述没有用术语“约”修饰。应当理解，无论是否明确地使用了术语“约”，本文所给出的每个量都意在指代实际的给定值，并且还意在指代由本领域的普通技术人员可合理推测出的这些给定值的近似值，包括这些给定值的由实验和/或测量条件所引起的近似值。
为了提供更简洁的描述，本文中一些数量表述被叙述为约X量至约Y量的范围。应当理解，当叙述范围时，该范围并不限制于所叙述的上下界限，而应包括约X量至约Y量的整个范围或它们之间的任何量。
青蒿提取物
青蒿为菊科黄花蒿Artemisia annua L.的全草。性苦、寒。归肝、胆、肾经。有清虚热，解暑截疟的作用。青蒿含有抗疟成分青蒿素，可直接杀灭疟原虫，现代研究表明，青蒿提取物具有抑菌杀虫、解热抗炎、调节免疫的作用，同时还具有5种抗氧化活性的黄酮类成分，包括槲皮素等。
在一些实施方式中，采用超声提取法提取青蒿提取物。超声提取特点包括：1.缩短提取时间，每次超声只需要20min-30min，常规提取基本上1h-1.5h；2.常温提取，不破坏热敏成分；3.直接细胞破壁，有效成分提取较完全。在优选的实施方式中，超声提取的工艺参数如下：提取2次，每次20min，超声3s，间隙3s。在一些实施方式中，提取溶剂是水(例如，去离子水)。在一些实施方式中，提取过程包括醇沉步骤。例如，采用95％的乙醇实现醇沉。在一些实施方式中，提取过程包括过滤步骤。在一些实施方式中，提取过程包括离心步骤。在一些实施方式中，提取过程还包括浓缩步骤。例如，浓缩至固含5-20重量％。在一个具体的实施方式中，浓缩至固含10.94重量％。
水溶性成分
本发明意外地发现，青蒿提取物和水溶性成分(例如白鲜皮提取物和醋卤提取物)复配，在皮肤抗敏、抗炎和/或抗刺激方面有较好的协同作用。因此，可以将青蒿提取物与水溶性成分组合使用，实现皮肤抗敏、抗炎和/或抗刺激效果。
在一些实施方式中，水溶性成分是白鲜皮提取物。在一些实施方式中，白鲜皮提取物采用超声提取物法制备。例如，可以采用北京弘祥隆生物技术股份有限公司的TGCXN-2B型设备制备得到。在一些实施方式中，白鲜皮提取物采用乙醇(例如，70-90％的乙醇)进行提取。在优选的实施方式中，采用80％乙醇提取。在一些实施方式中，白鲜皮提取物的制备还包括离心过滤的步骤。在一些实施方式中，白鲜皮提取物的制备还包括浓缩步骤。
在一些实施方式中，本发明提供了包含青蒿提取物与白鲜皮提取物的组合物，其中，青蒿提取物与白鲜皮提取物的重量比为1∶4至4∶1。在优选的实施 方式中，青蒿提取物与白鲜皮提取物的重量比为1∶2至2∶1。在优选的实施方式中，青蒿提取物与白鲜皮提取物的重量比为1∶1至2∶1。
在一些实施方式中，水溶性成分是醋卤提取物。在一些实施方式中，醋卤由江苏江苏恒顺集团有限公司提供。
在一些实施方式中，采用以下方法制备醋卤提取物：
(a)将糯米粉碎，蒸煮，经糖化后加入酵母菌和麦曲进行酒醪发酵，得到酒醪；
(b)加入麦麸和稻壳，搅拌均匀，接入固态种子醅和复合微生物菌种进行醋醅固态分层发酵，得到醋醅；
(c)取醋醅底部自然渗出的醋卤，得到醋卤；
(d)醋卤经树脂分离洗脱，得到醋卤提取物。
在优选的实施方式中，所述步骤(d)采用的树脂选自以下：非极性大孔树脂、弱极性大孔树脂、极性大孔树脂中的任一种。在优选的实施方式中，所述非极性大孔树脂是D101树脂、所述弱极性大孔树脂是AB-8树脂、所述极性大孔树脂是DM301树脂。在优选的实施方式中，所述步骤(d)采用水或乙醇洗脱。在优选的实施方式中，所述步骤(d)采用50-70体积％的乙醇洗脱。
在一些实施方式中，醋卤提取物根据申请人的相关专利申请202111158651.X的实施例5中描述的方法进行制备。在一个具体的实施方式中，取醋卤100g，加2-10倍去离子水稀释后，加入100gAB-8树脂，室温静态吸附，过滤分离出树脂，分别以去离子水洗脱、以50％乙醇洗脱，收集50％洗脱液，浓缩、干燥，得到醋卤提取物2.05g，备用。
在一些实施方式中，本发明提供了包含青蒿提取物与醋卤提取物的组合物，其中，青蒿提取物与醋卤提取物的重量比为2∶1至60∶1。在优选的实施方式中，青蒿提取物与醋卤提取物的重量比为10∶1至60∶1。在优选的实施方式中，青蒿提取物与醋卤提取物的重量比为50∶1至60∶1。
皮肤外用剂
本发明包含青蒿提取物与水溶性成分的组合物可以作为复合功效添加剂 应用于皮肤外用剂中。在一些实施方式中，所述皮肤外用剂选自：洁面乳、化妆水、乳液、膏霜、啫喱、面膜。根据制剂的不同类型添加不同的用量。
另一方面，提供了一种皮肤外用剂，所述皮肤外用剂包含青蒿提取物与水溶性成分的组合物及化妆品领域可接受的赋形剂。
所述皮肤外用剂是通常用于皮肤外部的所有成分的统称概念，例如可以是化妆品组合物或药物组合物。所述化妆品组合物中可以是基础化妆品、面部妆容化妆品、身体用化妆品、头发护理用化妆品等，对其剂型无特殊限制，根据不同目的可合理选择。所述化妆品组合物中根据剂型和目的的不同还含有不同的化妆品学层面允许的介质或基质赋形剂。
皮肤外用剂含有皮肤学上可接受的载体或媒介物(例如，洗液、面霜、软膏、清洁剂等等)。本领域普通技术人员能够根据本领域公知常识，选择能够以上文所述的浓度溶解或分散这些组分的载体。当使用一种载体时，该载体应当不会导致青蒿提取物或水溶性成分的灭活，而且在使用时不会在皮肤上带来任何相反的作用。
本领域普通技术人员能够根据公知常识和它们以最适用于处理时活性组分的浓度而溶解或分散在活性组分中的能力来选择适宜的载体，所述载体例如包括水、醇类、油等。
本发明的皮肤外用剂可以是局部施用产品的形式，其能够从外部施用在皮肤上，并能够以本领域公知的那些普通技术制备。载体可以具有各种实际的形式，例如面霜，敷料，凝胶，洗液，软膏或者液体，其包括敷用和清洗掉的组合物，以及用本领域公知的方法将它们加入到例如干的或湿的涂抹物，水凝胶基质，或粘性(或非粘性)贴片的材料载体中。优选地，载体是一种凝胶或增加水分的洗剂，或者以干或湿的形式的涂抹物。
典型的载体包括包含水和/或醇和润肤剂的乳剂，其中润肤剂是例如烃的油和蜡，硅油，透明质酸，植物、动物或海洋生物的脂肪或油，甘油酯衍生物，脂肪酸、或脂肪酸酯或醇或醇醚，羊毛脂及其衍生物，多元醇或酯，蜡酯，甾醇，磷脂等等，一般还有乳化剂(非离子的，阳离子的或阴离子的)，尽管一些润肤剂本身具有乳化特性。另外，可以利用其组分的不同比例和/或通过掺入例如树胶或其他形式的亲水胶体的增稠剂将这些相同组分配制成面霜、凝胶、或 固体棒。
本发明的皮肤外用剂可以包含在皮肤护理组合物中通常能找到的附加组分，例如润肤剂、皮肤调节剂、乳化剂、防腐剂、抗氧化剂、香料、螯合剂等，只要它们与皮肤外用剂中其他的组分在物理上和化学上相容即可。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种防腐剂。适宜的防腐剂包括对羟基苯乙酮、C1-C4对羟基苯甲酸烷基酯和苯氧基乙醇。基于组合物总重量，防腐剂的用量为大约0.5至大约2重量％，优选大约0.5至1重量％。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种抗氧化剂。适宜的抗氧化剂包括丁化羟基甲苯(BHT)、抗坏血酸棕榈酸酯(BHA)、丁羟茴醚、苯基-α-萘基胺、氢醌、没食子丙酯、去甲二氢愈创木酸、维生素E或维生素E的衍生物、维生素C及其衍生物、泛酸钙、绿茶提取物和混合的多酚，以及上面所述的物质的混合物。所使用的抗氧化剂是组合物总重量的大约0.02至0.5重量％，更最优选的是从大约0.002至0.1重量％的用量范围。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种润肤剂，通过其保持在皮肤表面上或在角质层中的能力，起到润滑剂的作用，以减少剥落，改善皮肤的外观。典型的润肤剂包括脂肪酯、脂肪醇、矿物油、聚醚硅氧烷共聚物等等。适宜的润肤剂的例子非限定地包括，聚丙二醇(“PPG”)-15十八烷基醚，PPG-10十六烷基醚，Steareth-10，Oleth-8，PPG-4十二烷基醚，维生素E醋酸酯，羊毛脂，鲸蜡醇，鲸蜡硬脂醇乙基己酸酯，十六十八醇，甘油硬脂酸酯，羟基硬脂酸辛脂，二甲基聚硅氧烷，以及它们的组合。鲸蜡醇，鲸蜡硬脂醇乙基己酸酯，十六十八醇，甘油硬脂酸酯以及它们的组合是优选的。使用时，润肤剂是基于组合物总重量的大约0.1至大约30重量％，优选大约1至大约30重量％的用量范围。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种保湿剂。保湿剂也称为湿润剂，其有助于提高润肤剂的效果，减少剥落，刺激组成的鳞皮的去除和提高皮肤触感。可使用多元醇作为保湿剂，包括但并不限于，甘油，聚亚烷基二醇，亚烷基多元醇及其衍生物，包含丁二醇、丙二醇、双丙二醇，聚丙三醇，聚乙二醇及其衍生物，山梨醇，羟丙基山梨醇，己二醇，1，3-二丁 二醇，1，2，6-己三醇，乙氧基化甘油，丙氧基化甘油，以及它们的组合。使用时，基于组合物的总重量，保湿剂的用量为大约0.1至大约20重量％，优选是大约1至大约15重量％。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种乳化剂。乳化剂可在有效稳定量的范围内使用。优选地，在组合物总重量的基础上，以大约1.0至大约10.0重量％，更优选的是大约3.0至大约6.0重量％的用量来使用乳化剂。可以使用任何与组合物中的组分相容的乳化剂。适宜的乳化剂包括硬脂酸，鲸蜡醇，甘油硬脂酸酯，卵磷脂，十八烷醇，Steareth-2，Steareth-20，丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物，以及它们的组合。
在本发明的皮肤外用剂的一些实施方式中，可使用一种或多种pH调节剂。本发明的皮肤外用剂中有益的pH调节剂包括氨丁三醇。使用时，基于组合物的总重量pH调节剂的用量为大约0.1至大约2重量％，优选是大约0.1至大约1重量％。
在本发明的一些实施方式中，皮肤外用剂包含丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物、甘油、对羟基苯乙酮、甘油硬脂酸酯和卵磷脂、十六/十八醇、鲸蜡硬脂醇乙基己酸酯、氨丁三醇或它们的组合。
在本发明的一些实施方式中，皮肤外用剂中青蒿提取物与水溶性成分的组合物的用量为0.001％-0.2％(w/w)，优选的重量百分比为0.007％-0.1％(w/w)，更优选的重量百分比为0.007％-0.08％(w/w)，最优选的重量百分比为0.007％-0.056％(w/w)。
实施例
下面结合具体实施例，以进一步阐述本发明。有必要在此指出的是，实施例只用于对本发明进行进一步的说明，不能理解为对本发明保护范围的限制，该领域的技术熟练人员可以根据上述本发明的内容做出一些非本质的改进和调整。下列实施例中未注明具体条件的试验方法，通常按照常规条件，或按照制造厂商所建议的条件。除非另有说明，所有的百分比和份数按重量计。
以下实施例中采用的实验材料如下：
实施例1：青蒿提取物的制备
称取青蒿100g，用1倍去离子水超声提取2次，过滤，煎煮浓缩，加入95％乙醇醇沉(终浓度70％)，滤纸(新星牌定性滤纸，规格60*60cm)过滤，滤液于55℃条件下浓缩，4℃静置过夜，取出3℃ 3500rpm条件下离心15min(卢湘仪，DL-5M)，滤纸过滤，最终配制成固含10.94％溶液，备用。
实施例2：青蒿提取物的制备
取实施例1制备的固含10.94％青蒿提取物样品10.94g，加入去离子水，配制成固含1％溶液，备用。
实施例3：白鲜皮提取物制备
称取白鲜皮100g，打粗粉，用10倍80％乙醇超声提取(北京弘祥隆生物技术股份有限公司，TGCXN-2B)2次，每次20min，离心过滤，合并滤液于55℃条件下浓缩，4℃静置过夜。取出3℃3500rpm条件下离心15min，滤纸过滤，最终配制成固含9.75％溶液，备用。
实施例4：白鲜皮提取物配制
取实施例3制备的固含9.75％白鲜皮提取物样品9.75g，加入去离子水，配制成固含1％溶液，备用。
实施例5：醋卤提取物配制
醋卤提取物按照中国专利申请CN 202111158651.X(糯米发酵提取物及其抗衰老应用)的实施例5制备。具体而言，取醋卤100g，加2-10倍去离子水稀释后，加入100gAB-8树脂，室温静态吸附，过滤分离出树脂，分别以去离子水洗脱、以50％乙醇洗脱，收集50％洗脱液，浓缩、干燥，得到醋卤提取物2.05g，加去离子水溶解，配制成固含1％溶液，备用。
实施例6：青蒿提取物的制备
将实施例1提取物：实施例3提取物按照重量比1∶1混合制备，备用。
实施例7：青蒿提取物的制备
将实施例1提取物：实施例3提取物按照重量比1∶3混合制备，备用。
实施例8：青蒿提取物的制备
将实施例1提取物：实施例3提取物按照重量比3∶1混合制备，备用。
实施例9：青蒿提取物的制备
将实施例1提取物：实施例5提取物按照重量比1∶1混合制备，备用。
实施例10：青蒿提取物的制备
将实施例1提取物：实施例5提取物按照重量比1∶5混合制备，备用。
实施例11：青蒿提取物的制备
将实施例1提取物：实施例5提取物按照重量比5∶1混合制备，备用。
实施例12：透明质酸酶活性抑制评价
取59ml冰醋酸(国药试剂，分析纯)加水稀释至1000ml，用玻璃棒搅拌均匀，再用10倍水稀释配制成0.1mol/L的溶液A，备用。取8.203g无水乙酸钠(国药试剂，分析纯)溶于1000ml水中，用玻璃棒搅拌均匀，再用10倍水稀释配制成0.1mol/L的溶液B，备用。按溶液A∶溶液B体积比16∶1，最终配制成pH3.5的乙酸-乙酸钠缓冲液(以下简称Buffer缓冲液)，备用。
取透明质酸酶(活力≥560units/mg，sigma)0.1411g，用10ml Buffer缓冲液配制成酶活≥7900units/ml的透明质酸酶溶液，临用配制。
取无水氯化钙(国药试剂，分析纯)0.1387g，用100ml水配制成12.5mmol/L的氯化钙溶液，备用。
取透明质酸钠(东辰集团)0.12g，用100ml Buffer缓冲液配制成1.2mg/ml的透明质酸钠溶液，备用。
取氢氧化钠(国药试剂，分析纯)0.4g，用25ml水配制成0.4mol/L的氢氧化钠溶液，备用。
取四硼酸钾(国药试剂，分析纯)30.55g，用250ml水配制成0.4mol/L的硼酸钾溶液，备用。
取浓盐酸(国药试剂，分析纯)41.4ml，用8.5ml水配制成10mol/L的盐酸溶液，备用。
取对二甲氨基苯甲醛(国药试剂，分析纯)4g，先加入350ml冰醋酸，再加入50ml 10mol/L盐酸，配制成10mg/ml的对二甲氨基苯甲醛溶液，备用。
取制备好的实施例2-11提取物或溶液，以缓冲液各自稀释，按表1方法进行试验，于585nm处测吸光值，最终计算其IC50。
表1
实验结果：
根据以下公式计算透明质酸酶的抑制率：
其中T为样品，T0为样品对照，C为空白，C0为空白对照。
根据皮肤外用剂场景下的实际应用，可以认为IC50＜10mg/ml属于优秀，IC50＜30mg/ml属于良好，IC50＜50mg/ml属于一般，IC50≥50mg/ml基本上没有应用价值。
表2
表3
表4
由透明质酸活性抑制实验结果可知，实施例2、4提取物作为单味药具有一定的抑制透明质酸酶能力，实施例5提取物较弱抑制透明质酸酶能力，然而当青蒿提取物与白鲜皮提取物、醋卤提取物复配时，均在一定程度上改善抑制透明质酸酶活性的能力。
同时根据不同复方比例配比抑制透明质酸酶浓度结果可知，实施例6即青蒿提取物与白鲜皮提取物复配比例为1∶1时，IC50浓度小于单味药浓度，优选实施例6。
另实施例11即青蒿提取物与醋卤提取物复配比例为5∶1，IC50浓度小于单味药浓度；实施例9即青蒿提取物与醋卤提取物复配比例为1∶1，IC50浓度与实施例2浓度相近，可优选实施例11，次选实施例9。
进一步分析可知，由于实施例6～11中青蒿重量占比不同，换算后不同复方配比中实际青蒿IC50浓度如表3、表4所示，可以发现实施例6、7、9、11中实际青蒿IC50浓度均小于单独青蒿IC50浓度，从而在本质上降低了配方功效添加量，进而可以降低成本。
实施例6-11的制备物可用于皮肤外用剂的制备。所述皮肤外用剂优选为化妆品组合物，例如化妆水、精华液、乳霜等。所述制备物在皮肤外用 剂中的重量百分比为0.026％-1.5％(w/w)。优选的重量百分比为0.026％-0.96％(w/w)。更优选的重量百分比为0.052％-0.74％(w/w)。最优选的重量百分比为0.1％-0.48％(w/w)。
以下是实施例的制备物在皮肤外用剂中的具体应用例，以及这些剂型的配方和制备方法。以下各表中“-”表示无添加。
实施例13：面霜的制备
实施例14：乳液的制备

实施例15：啫喱的制备

实施例16：化妆水的制备
实施例17：精华液的制备

实施例18：面膜的制备
实施例19：眼霜的制备
实施例20：气雾(清洁泡)的制备

实施例21：喷雾的制备
实施例22：沐浴露的制备

实施例23：洗面奶的制备

Claims (12)

  1. 包含青蒿提取物和水溶性成分的组合物在皮肤抗敏、抗炎和/或抗刺激中的应用，其中，所述水溶性成分选自白鲜皮提取物和醋卤提取物。
  2. 如权利要求1所述的应用，其中，所述青蒿提取物采用超声提取法制备。
  3. 如权利要求1所述的应用，其中，所述青蒿提取物采用水作为溶剂提取。
  4. 如权利要求1所述的应用，其中，所述醋卤提取物通过以下方法制备得到：
    (a)将糯米粉碎，蒸煮，经糖化后加入酵母菌和麦曲进行酒醪发酵，得到酒醪；
    (b)加入麦麸和稻壳，搅拌均匀，接入固态种子醅和复合微生物菌种进行醋醅固态分层发酵，得到醋醅；
    (c)取醋醅底部自然渗出的醋卤，得到醋卤；
    (d)醋卤经树脂分离洗脱，得到醋卤提取物。
  5. 如权利要求1所述的应用，其中，所述白鲜皮提取物采用超声提取法制备。
  6. 如权利要求1所述的应用，其中，所述水溶性成分是白鲜皮提取物，青蒿提取物与白鲜皮提取物的重量比为1∶4至4∶1。
  7. 如权利要求1所述的应用，其中，所述水溶性成分是醋卤提取物，青蒿提取物与醋卤提取物的重量比为2∶1至60∶1。
  8. 如权利要求1-7中任一项所述的应用，其中，所述抗炎、抗敏和/或抗刺激作用通过抑制透明质酸酶实现。
  9. 如权利要求1-7中任一项所述的应用，用于辅助止痒和/或湿疹问题。
  10. 包含青蒿提取物和水溶性成分的组合物在制备具有皮肤抗敏、抗炎和/或抗刺激作用的皮肤外用剂中的应用，其中，所述水溶性成分选自白鲜皮提取物和醋卤提取物。
  11. 如权利要求10所述的应用，其中，所述皮肤外用剂选自：面霜、乳液、啫喱、化妆水、精华液、面膜、眼霜、气雾洁面泡、喷雾、沐浴露、洗面奶。
  12. 如权利要求10所述的应用，其中，所述皮肤外用剂包含0.08-1重量％的包含青蒿提取物和水溶性成分的组合物。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1513515A (zh) * 2003-07-05 2004-07-21 昆明医学院第一附属医院 治疗皮肤病的药物及其制备方法
KR20040076005A (ko) * 2003-02-24 2004-08-31 김종규 약쑥을 모체로 한 한방의 고농축 액상물질과 이의 스프레이/에어로졸 용기 가공체
CN108704021A (zh) * 2018-08-14 2018-10-26 石家庄仁美医疗器械销售有限公司 用于皮肤过敏及皮肤屏障受损的组合物及制备方法
CN113679765A (zh) * 2021-09-30 2021-11-23 上海家化联合股份有限公司 白鲜皮提取物及其应用
CN113855718A (zh) * 2021-09-30 2021-12-31 上海家化联合股份有限公司 青蒿提取物及其应用
CN113855609A (zh) * 2021-09-30 2021-12-31 上海家化联合股份有限公司 糯米发酵提取物及其抗湿疹应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040076005A (ko) * 2003-02-24 2004-08-31 김종규 약쑥을 모체로 한 한방의 고농축 액상물질과 이의 스프레이/에어로졸 용기 가공체
CN1513515A (zh) * 2003-07-05 2004-07-21 昆明医学院第一附属医院 治疗皮肤病的药物及其制备方法
CN108704021A (zh) * 2018-08-14 2018-10-26 石家庄仁美医疗器械销售有限公司 用于皮肤过敏及皮肤屏障受损的组合物及制备方法
CN113679765A (zh) * 2021-09-30 2021-11-23 上海家化联合股份有限公司 白鲜皮提取物及其应用
CN113855718A (zh) * 2021-09-30 2021-12-31 上海家化联合股份有限公司 青蒿提取物及其应用
CN113855609A (zh) * 2021-09-30 2021-12-31 上海家化联合股份有限公司 糯米发酵提取物及其抗湿疹应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEN, YIMIN: "Study on Efficacy of Dictamnus dasycarpus Decoction in Treatment of 18 Cases of Tinea Pedis", JOURNAL OF MIANYANG TEACHERS' COLLEGE (NATURAL SCIENCE EDITION), vol. 12, no. 2, 31 October 1994 (1994-10-31) *

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