WO2021017910A1 - 具有增强的抗炎功效的皮肤外用组合物 - Google Patents

具有增强的抗炎功效的皮肤外用组合物 Download PDF

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WO2021017910A1
WO2021017910A1 PCT/CN2020/102862 CN2020102862W WO2021017910A1 WO 2021017910 A1 WO2021017910 A1 WO 2021017910A1 CN 2020102862 W CN2020102862 W CN 2020102862W WO 2021017910 A1 WO2021017910 A1 WO 2021017910A1
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composition
skin
external
group
external skin
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PCT/CN2020/102862
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English (en)
French (fr)
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魏双萍
王莎莎
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浙江养生堂天然药物研究所有限公司
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Priority to KR1020227006730A priority Critical patent/KR20220044765A/ko
Priority to JP2022506257A priority patent/JP7320666B2/ja
Publication of WO2021017910A1 publication Critical patent/WO2021017910A1/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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • 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)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • 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
    • 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
    • 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
    • A61Q19/008—Preparations for oily skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • 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
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/591—Mixtures of compounds not provided for by any of the codes A61K2800/592 - A61K2800/596

Definitions

  • the present invention relates to a skin topical composition with enhanced anti-inflammatory effect, which comprises (A) concentrated birch tree juice with a concentration factor of about 1.05-8 times, preferably about 1.1-4 times, more preferably about 1.2- 2 times, and (B) one or more substances selected from oat kernel extract, panthenol, allantoin, bisabolol and dipotassium glycyrrhizinate.
  • Birch is a deciduous tree of the birch family. There are currently about 100 species in the world, mainly distributed in the northern temperate zone and the cold temperate zone. Among them, there are about 29 varieties in my country, mainly distributed in the northeast, northwest, north and southwest. Birch trees are mostly grown in remote mountainous areas with little human intervention and no industrial pollution. Birch sap (also called birch sap) is the fresh sap from the birch bark being cut or the trunk is drilled. It is colorless or light yellow, free of precipitation and impurities, and has a light birch fragrance. The birch sap contains a lot of sugars, amino acids, vitamins, biotin, cytokinins, trace mineral elements, aromatic oils, betulin, saponin and other compounds. It has good moisturizing, anti-inflammatory, anti-wrinkle and whitening properties. And other skin care effects.
  • the present invention relates to a combination of (A) concentrated birch tree juice and (B) one or more selected from the group consisting of oat kernel extract, panthenol, allantoin, bisabolol and dipotassium glycyrrhizinate.
  • concentration factor of the concentrated birch tree juice is about 1.05-8 times, preferably about 1.1-4 times, more preferably about 1.2-2 times.
  • the present invention relates to a skin external composition with enhanced anti-inflammatory effect, which comprises (A) concentrated birch tree sap, the concentration of which is about 1.05-8 times, preferably about 1.1-4 times, more It is preferably about 1.2-2 times, and (B) one or more substances selected from oat kernel extract, panthenol, allantoin, bisabolol and dipotassium glycyrrhizinate.
  • the birch sap involved in the present invention is derived from the genus Betula, Betula alba, Betula pubescens, Betula Pendula and Asian white birch (Betula platyphylla). Varieties.
  • the birch sap is a colorless, transparent, no-sediment-free, and no-drug sap that is artificially collected by drilling holes at the base of the trunk of the birch from thawing to early spring.
  • the birch sap is commercially available and used as it is, for example, it can be purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd.
  • the concentrated birch sap in the present invention is obtained by concentrating the above-mentioned commercial products. Concentration methods are known in the art, such as heating concentration, low-temperature vacuum concentration, membrane concentration and the like. In the present invention, the concentration is preferably carried out by a low-temperature freeze concentration or membrane concentration process. For example, the commercially available birch juice stock solution is input into a low-temperature drying equipment, the temperature is lowered to -40°C to -70°C, and the vacuum is applied to 0.1-30Pa. Concentrated in vacuum at low temperature to obtain concentrated birch sap with different concentration times.
  • controlling the concentration factor of birch sap is critical.
  • controlling the concentration factor of birch sap is 1.05-8 times, preferably about 1.1-4 times, more preferably about 1.2-2 times.
  • the present inventors found that compared with the use of concentrated birch sap, oat kernel extract, panthenol, allantoin, bisabolol or dipotassium glycyrrhizinate alone, the concentrated birch sap and oat kernel extract
  • the combination of substances, panthenol, allantoin, bisabolol and/or dipotassium glycyrrhizinate has a significantly better anti-inflammatory effect, which is much higher than the combined effect of the two functions, which indicates that a synergistic effect has occurred between them .
  • the content of the concentrated birch sap of the component (A) is about 18-98% by weight, preferably about 20-95% by weight, more preferably about 22-90% by weight, most preferably about 30-90% by weight, based on The total weight of the external skin composition.
  • the component (B) oatmeal extract, panthenol, allantoin, bisabolol or dipotassium glycyrrhizinate are all substances known in the art and all are commercially available.
  • the content of the component (B) is about 0.01-10%, preferably about 0.1-6%, more preferably about 0.5-5%, based on the total weight of the skin external composition.
  • the external skin composition includes a pharmaceutical composition or a cosmetic composition.
  • the external skin composition does not contain any added water, but does not exclude the moisture inherently contained in each component.
  • the external skin composition does not contain chelating agents such as EDTA salt, sodium polyphosphate, sodium metaphosphate, and gluconic acid.
  • chelating agents such as EDTA salt, sodium polyphosphate, sodium metaphosphate, and gluconic acid.
  • the skin external composition may optionally contain component (C) commonly used ingredients in skin external compositions, including but not limited to vehicles, active ingredients and Accessories etc.
  • component (C) commonly used ingredients in skin external compositions, including but not limited to vehicles, active ingredients and Accessories etc.
  • Component (C) is known in the art, and those skilled in the art can select its type and amount according to needs. For example, the total content of component (C) is usually about 2-80%, based on the skin external composition The total weight.
  • the vehicle includes, for example, a diluent, a dispersant, or a carrier, and examples thereof include, but are not limited to, ethanol, dipropylene glycol, butylene glycol, and the like.
  • the content of the vehicle in the skin topical composition is known in the art, for example, it usually accounts for 0.5-20% of the total weight of component (C).
  • the active ingredients include, for example, emollients, moisturizers, other anti-inflammatory active ingredients and the like.
  • emollients include, but are not limited to, olive oil, macadamia oil, sweet almond oil, grape seed oil, avocado oil, corn oil, sesame oil, soybean oil, peanut oil, white flower seed oil, safflower seed oil, Dogtooth rose hip oil, argan argan oil, jojoba seed oil, sunflower seed oil, palm tree oil, ethylhexyl palmitate, isopropyl myristate, hydrogenated polyisobutylene, isohexadecane, isohexadecane Dodecane, diethylhexyl carbonate, dioctyl carbonate, isopropyl lauroyl sarcosine, isononyl isononanoate, hydrogenated polydecene, glycerol tri(ethylhexanoate), cetyl alcohol Ethylhexanoate, bis-diethoxydiethylene glycol cyclohexane 1,4-dicar
  • solid emollients include, but are not limited to, cetyl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, scylitol, lauric acid, myristic acid, palmitic acid, stearic acid, beeswax, candelilla Tree wax, carnauba wax, lanolin, ozokerite, jojoba seed wax, paraffin wax, microcrystalline wax, hydrogenated rice bran wax, hydrogenated coconut oil glycerides, glyceryl behenate/eicosanate, myristyl alcohol One or more of myristate, bis-diglyceride polyacyl adipate-2, shea butter, and muluxing palm seed butter.
  • the content of the emollient in the skin external composition is known in the art, for example, it usually accounts for 1-50% of the total weight of the component (C).
  • moisturizer examples include, but are not limited to, glycerin, diglycerin, butylene glycol, propylene glycol, 1,3-propanediol, dipropylene glycol, 1,2-pentanediol, polyethylene glycol-8, polyethylene glycol Alcohol-32, methylglucitol-10, methylglucitol-20, PEG/PPG-17/6 copolymer, glycerol-7, glycerol-26, glycerol glucoside, PPG-10 methyl glucose ether, PPG-20 methyl glucose ether, PEG/PPG/polybutylene glycol-8/5/3 glycerin, sucrose, trehalose, rhamnose, mannose, raffinose, Betaine, erythritol, xylitol, urea, glyceryl polyether-5 lactate, sodium hyaluronate, hydrolyzed sodium hyaluronate, acetyl
  • anti-inflammatory active ingredients examples include, but are not limited to, Portulaca oleracea extract, biocarbohydrate gum-1, ⁇ -glucan, fructan, Scutellaria baicalensis root extract, European seven Leaf tree (AESCULUS HIPPOCASTANUM) extract, 4-tert-butylcyclohexanol, hydrogenated lecithin, GLYCYRRHIZA GLABRA extract, hydrolyzed royal jelly protein, oryzanol, sphingosine, quercetin, quercetin, One or more of ginger root extract, rosemary leaf extract, etc.
  • the content of the anti-inflammatory active ingredient in the skin external composition is known in the art, for example, it usually accounts for 0.01-10% of the total weight of the component (C).
  • the auxiliary materials include, for example, emulsifiers, thickeners, preservatives, perfumes and the like.
  • emulsifier examples include, but are not limited to, cetearyl oleate, sorbitan oleate, polysorbate-60, polysorbate-80, methylglucose sesquistearic acid Ester, PEG-20 methyl glucose sesquistearate, PEG-40 hydrogenated castor oil, PPG-26-butanol-26, PEG-4 polyglycerol-2 stearate, PEG-60 hydrogenated Castor oil, steareth-2, steareth-21, PPG-13-decyltetradeceth-24, cetearyl glucoside, PEG-100 stearate, glycerin Stearate, Glyceryl Stearate SE, Coco Glucoside, Ceteareth-25, PEG-40 Stearate, Polyglyceryl-3 Methyl Glucose Distearate, Glyceryl stearate citrate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, polyglyce
  • the thickener examples include, but are not limited to, carbomers, acrylic acid (ester) and its derivatives, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinyl poly One or more of high molecular polymers such as sugar, hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.
  • the content of the thickener in the external skin composition is known in the art, for example, it usually accounts for 0.1-10% of the total weight of the component (C).
  • preservatives examples include, but are not limited to, methylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenethyl alcohol, bis(hydroxymethyl)imidazolidinylurea, potassium sorbate, sodium benzoate, chlorobenzene Glycerol, sodium dehydroacetate, caprylic hydroxamic acid, 1,2-hexanediol, 1,2-pentanediol, p-hydroxyacetophenone, caprylyl glycol, glyceryl caprylate, undecylenic acid
  • the content of the preservative in the external skin composition is known in the art, for example, it usually accounts for 0.01-2% of the total weight of the component (C).
  • the skin external composition of the present invention can be prepared by any suitable method known in the art.
  • it can be prepared by dissolving tanks, emulsifying pots, dispersers, and delivery pumps commonly used in the cosmetics field.
  • the water-soluble substance into the water-phase dissolving kettle, and the oil-soluble substance into the oil-phase dissolving kettle, and heat the temperature of the two kettles to about 80°C.
  • a disperser Pre-dispersion. After the dissolution is completed, the oil phase and the water phase are transported to the emulsifying pot for homogenization and emulsification for about 5-15 minutes. After the emulsification is completed, the temperature of the material body is reduced to normal temperature, optional flavors, preservatives, etc. are added, and the pH of the product is adjusted as necessary.
  • the products can be filled and shipped only after the relevant test indicators are qualified.
  • the external skin composition can be made into various dosage forms such as creams, creams, lotions, essences, sprays, and gels.
  • Example 1 The influence of different material systems on irritant contact dermatitis
  • This example is based on a mouse model of irritant contact dermatitis to evaluate the anti-inflammatory effects of birch sap stock, concentrated birch sap, oat kernel extract and/or.
  • mice were randomly grouped according to body weight, each with 12 mice, divided into normal group, model group, and each formula group.
  • mice in each group were treated with depilatory cream to remove skin and hair on the abdomen area of about 2x2cm.
  • the model group and each formula group on the day of modeling, use a pipette to draw 50 ⁇ L of 10% sodium lauryl sulfate solution and apply evenly to the exposed skin of the mouse abdomen for 5 consecutive days.
  • the solutions of each formula group were sprayed with the same aerosol bottle, and each spray was evenly sprayed 2 times each time, 3 times a day for 2 consecutive days.
  • mice in the normal group were treated with the same method to remove the mouse hairs from their abdomen and were raised for 7 days for control.
  • the skin conditions of the experimental mice in each group were observed, and the serum of the mice was taken to determine the content of the inflammatory factor IL-1 ⁇ .
  • the 1.2 times, 4 times, and 9 times birch sap concentrates are obtained by concentrating the birch sap raw liquid.
  • the concentration process is: the fresh white birch sap raw liquid purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd. is input into low-temperature drying Equipment, cooling down to -65°C, vacuuming to 0.1Pa, and concentration to 1.2 times, 4 times, and 9 times.
  • mice After treatment with different formula systems, the serum inflammatory factor IL- ⁇ content of mice is shown in the following table:
  • Example 2 The effect of different cosmetic composition systems on allergic contact dermatitis
  • mice were randomly grouped by body weight, each group was 12 Only, divided into normal group, model group, and formula group. In each group of experimental mice, one day before modeling, depilatory cream was used to remove the skin and hair of the mouse's abdomen with an area of about 2x2cm. In the model group and each formula group, on the day of modeling, 100 ⁇ L of acetone olive oil solution containing 1% DNFB was evenly smeared on the exposed skin of the abdomen of the mice for sensitization and stimulation to establish a mouse model of allergic contact dermatitis.
  • mice Apply for 2 consecutive days, and on the 5th day, evenly apply 20 ⁇ L of 1% DNFB acetone olive oil solution to the inner and outer ear surfaces of the mice for excitation.
  • the abdomen and ears of mice in the normal group were evenly coated with acetone and olive oil solution (4:1) for control.
  • the medication was started 12 hours after the challenge, and the same aerosol bottle was used for each formula group to spray the inside and outside of the ears of the experimental mice evenly, once inside and outside each ear, three times a day for 2 consecutive days.
  • the model group was sprayed with distilled water for 2 consecutive days, 3 times a day, and the inner and outer ears were repeatedly rubbed with a cotton swab for about 5 seconds.
  • Ear thickness index the mouse ear thickness was measured 12h and 48h after the challenge, and the average value of the ears was taken.
  • Ear weight index 2 days after the administration, the left ear disc of each experimental mouse was taken with a hole punch and weighed.
  • Inflammation index determination After 2 days of medication, the mouse serum was taken, and the inflammatory factors IFN- ⁇ , IL-4 and tryptase content in the mouse ear tissue were detected by ELISA kit, and IFN- ⁇ /IL-4 was calculated.
  • This example uses a zebrafish juvenile allergy model to test and compare the effects of birch sap and dipotassium glycyrrhizinate on mast cell degranulation, thereby verifying the anti-inflammatory effects of birch sap and dipotassium glycyrrhizinate.
  • the experimental method is as follows.
  • the experimental procedure is as follows: Collect AB wild-type zebrafish embryos, culture them with E3 buffer in a 28.5°C incubator to 5dpf (days post fertilization), and change the medium every day. Randomly transfer 5 dpf zebrafish juveniles to a 48-well cell culture plate with 10 tails per well for grouping. Each group has 4 replicate wells.
  • the grouping situation is as follows:
  • a negative control group (without SP) is set up, with 4 multiple holes in each group; corresponding to the SP degranulation induction group and the negative control group without SP, a background control group ( No zebrafish juveniles), 2 replicate holes per group. Blot the remaining E3 buffer in each group of wells and add 250 ⁇ l of the solution corresponding to each group, and react for 60 minutes in a 28.5°C incubator in the dark. After 60 minutes, 200 ul of the supernatant of each group was placed in a 96-well cell culture plate, and the enzyme reaction substrate BAPNA was added to make the concentration reach 400 ⁇ g/ml.
  • the 96-well plate was placed in a 28.5°C incubator for 2 hours in the dark and covered, and the light absorption value of the whole plate at 405nm was measured after 2 hours. The value reflects the release of tryptase from zebrafish mast cells.
  • the formula of the cream composition is as follows:
  • the above cream composition is prepared as follows:
  • the formula of the anti-inflammatory essence composition is as follows:
  • the above essence composition is prepared as follows:
  • raw material 1 into the emulsifying pot, and sprinkle raw materials 14 and 15 into the emulsifying pot while stirring. After raw materials 14 and 15 are completely swelled, add raw materials 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and raw material 13, heat up to 80°C while stirring, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;
  • the first group used the essence composition continuously
  • the second group used no birch Juice control product A (its formula is exactly the same as in the above table, but all birch sap is replaced by water)
  • the third group uses control product B (its formula is exactly the same as the above table, but all bisabolol, oatmeal Kernel extract is replaced by water).
  • Example 6 Anti-inflammatory emulsion composition
  • the formula of the anti-inflammatory emulsion composition is as follows:
  • the anti-inflammatory emulsion composition described above is prepared as follows:
  • the first group used the lotion composition continuously; the second group used no birch sap
  • the control product A (its formula is exactly the same as in the above table, but all birch sap is replaced by water); the third group uses control product B (its formula is exactly the same as the above table, but all dipotassium glycyrrhizinate, allantoic Is replaced by water).

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

一种具有增强的抗炎功效的皮肤外用组合物，其包含(A)浓缩的桦树汁，其浓缩倍数为约1.05-8倍，优选约1.1-4倍，更优选约1.2-2倍，和(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种物质。

Description

具有增强的抗炎功效的皮肤外用组合物 技术领域
本发明涉及一种具有增强的抗炎功效的皮肤外用组合物，其包含(A)浓缩的桦树汁，其浓缩倍数为约1.05-8倍，优选约1.1-4倍，更优选约1.2-2倍，和(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种物质。
背景技术
随着社会经济水平变化及化妆品种类与成分复杂化，敏感性皮肤出现及接受刺激的可能性增加；加上人们对皮肤健康意识及审美标准的提高，敏感皮肤的关注度逐渐上升。化妆品行业将把针对敏感性皮肤的产品摆在越来越重要的位置，并且已开发出针对敏感性皮肤各种原因和表现的活性物质抗敏成分。根据现有的市场调研，除了一些彩妆品牌，几乎所有的化妆品牌均推出了一定数目和不同类型的针对敏感性皮肤的产品。国外品牌，如雅漾、资生堂等知名品牌的产品种类多样。国内品牌佰草集也凭借“本草养肤”的差异化品牌形象而独树一帜。加之近几年出现的新兴的药妆品牌，如玉泽、薇诺娜等纯植物的药物化妆品。在这些“舒敏”的化妆品中均不同程度的添加了一些抗敏、抗刺激功效的植物提取物，如马齿苋、洋甘菊、茶多酚、蓝蓟油等，这些成分具有抗敏、抗炎和抗外界刺激的作用，可缓解肌肤过敏度，为肌肤提供天然保护屏障，有效修复受损的肌肤，激发细胞蛋白质生化合成以及细胞的再生，重建皮肤免疫系统。
桦树为桦木科落叶乔木，目前全球大约有100个品种，主要分布于北温带和寒温带。其中，我国境内约有29个品种，主要分布在东北、西北、华北和西南等地。桦树大多生长于人为干涉较少、且没有工业污染的边远山区。桦树汁(也称桦树液)是桦树树皮被划开或树干钻孔流出的新鲜汁液，无色或浅黄色，无沉淀及杂质，具有淡淡的桦树清香。桦树汁内含大量的糖类、氨基酸、维生素、生物素、细胞分裂素、微量的矿质元素、芳香油、桦树醇、皂角甙等化合物，具有良好的保湿、抗炎、抗皱、美白等护肤功效。
发明内容
一方面，本发明涉及(A)浓缩的桦树汁与(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种的组合在具有增强的抗炎功效的皮肤外用组合物中的用途，其中所述浓缩的桦树汁的浓缩倍数为约1.05-8倍，优选约1.1-4倍，更优选约1.2-2倍。
另一方面，本发明涉及一种具有增强的抗炎功效的皮肤外用组合物，其包含(A)浓缩的桦树汁，其浓缩倍数为约1.05-8倍，优选约1.1-4倍，更优选约1.2-2倍，和(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种物质。
本发明中所涉及的桦树汁得自桦木科桦树属，其可来自白桦(Betula alba)、柔毛桦 (Betula pubescens)、垂枝桦(Betula Pendula)和亚洲白桦(Betula platyphylla)这四个品种。所述桦树汁为在解冻至早春发叶之间，人工在桦树的树干基部钻孔收集而得的无色透明、无沉淀、无杂物，具有桦树清香营养丰富的汁液。所述桦树汁可商购获得并原样采用，例如可购自大兴安岭超越野生浆果开发有限责任公司。
本发明中的浓缩桦树汁是将上述商购产品浓缩得到的。浓缩方法是本领域已知的，例如加热浓缩、低温真空浓缩、膜浓缩等。在本发明中，优选通过低温冷冻浓缩或膜浓缩工艺进行浓缩，例如，将商购的桦树汁原液输入低温干燥设备，降温至-40℃至-70℃，抽真空至0.1-30Pa而进行低温真空浓缩，从而得到不同浓缩倍数的浓缩桦树汁。
进一步地，本发明人还发现，浓缩桦树汁的抗湿疹功效与其浓缩程度并非简单的线性关系，而是随着浓缩倍数增加而呈现先增加后下降的趋势。因此，控制桦树汁的浓缩倍数是关键的，在本发明中，控制桦树汁的浓缩倍数为1.05-8倍，优选约1.1-4倍，更优选约1.2-2倍。
意料不到地，本发明人发现，与单独使用浓缩桦树汁、燕麦仁提取物、泛醇、尿囊素、红没药醇或甘草酸二钾相比，浓缩桦树汁与燕麦仁提取物、泛醇、尿囊素、红没药醇和/或甘草酸二钾的组合具有显著更好的抗炎功效，远高于二者功能叠加效果，这表明它们之间发生了协同增效作用。
所述组分(A)浓缩的桦树汁的含量为约18-98％重量，优选约20-95％重量，更优选约22-90％重量，最优选约30-90％重量，基于所述皮肤外用组合物的总重量。
所述组分(B)燕麦仁提取物、泛醇、尿囊素、红没药醇或甘草酸二钾均是本领域已知的物质，均可商购获得。
所述组分(B)的含量为约0.01-10％，优选约0.1-6％，更优选约0.5-5％，基于所述皮肤外用组合物的总重量。
所述皮肤外用组合物包括药物组合物或者化妆品组合物。
所述皮肤外用组合物不包含任何外加的水，但不排除各组分中固有地包含的水分。
在优选的实施方案中，所述皮肤外用组合物不包含EDTA盐、多磷酸钠、偏磷酸钠、葡萄糖酸等螯合剂。
除了所述组分(A)和(B)外，所述皮肤外用组合物还可以任选地包含组分(C)皮肤外用组合物中常用的成分，包括但不限于媒介物、活性成分和辅料等。组分(C)是本领域已知的，本领域技术人员可根据需要选择其类型和用量，例如，组分(C)的总含量通常为约2-80％，基于所述皮肤外用组合物的总重量。
所述媒介物包括例如稀释剂、分散剂或载体等，其实例包括但不限于乙醇、双丙甘醇、丁二醇等。所述媒介物在所述皮肤外用组合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的0.5-20％。
所述活性成分包括例如润肤剂、保湿剂、其他抗炎活性成分等。
所述润肤剂的实例包括但不限于橄榄油、澳洲坚果油、甜杏仁油、葡萄籽油、鳄梨油、玉米油、芝麻油、大豆油、花生油、白池花籽油、红花籽油、狗牙蔷薇果油、刺阿干树仁 油、霍霍巴籽油、向日葵籽油、毛瑞榈果油、棕榈酸乙基己酯、肉豆蔻酸异丙酯、氢化聚异丁烯、异十六烷、异十二烷、碳酸二乙基己酯、碳酸二辛酯、月桂酰肌氨酸异丙酯、异壬酸异壬酯、氢化聚癸烯、甘油三(乙基己酸)酯、鲸蜡醇乙基己酸酯、双-二乙氧基二甘醇环己烷1,4-二羧酸酯、辛酸/癸酸甘油三酯、油醇芥酸酯、辛基十二醇肉豆蔻酸酯、辛基十二醇、聚二甲基硅氧烷、辛基聚甲基硅氧烷、鲸蜡基聚二甲基硅氧烷、环五聚二甲基硅氧烷等的一种或多种。固体润肤剂的实例包括但不限于鲸蜡醇、硬脂醇、鲸蜡硬脂醇、山嵛醇、鲨肝醇、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、蜂蜡、小烛树蜡、巴西棕榈蜡、羊毛脂、地蜡、霍霍巴籽蜡、石蜡、微晶蜡、氢化米糠蜡、氢化椰油甘油酯类、甘油山嵛酸酯/二十酸酯、肉豆蔻醇肉豆蔻酸酯、双-二甘油多酰基己二酸酯-2、牛油果树果脂、木鲁星果棕籽脂等中的一种或多种。所述润肤剂在所述皮肤外用组合物中的含量是本领域已知的，例如,其通常占组分(C)总重量的1-50％。
所述保湿剂的实例包括但不限于甘油、双甘油、丁二醇、丙二醇、1,3-丙二醇、双丙甘醇、1,2-戊二醇、聚乙二醇-8、聚乙二醇-32、甲基葡糖醇聚醚-10、甲基葡糖醇聚醚-20、PEG/PPG-17/6共聚物、甘油聚醚-7、甘油聚醚-26、甘油葡糖苷、PPG-10甲基葡糖醚、PPG-20甲基葡糖醚、PEG/PPG/聚丁二醇-8/5/3甘油、蔗糖、海藻糖、鼠李糖、甘露糖、棉子糖、甜菜碱、赤藓醇、木糖醇、尿素、甘油聚醚-5乳酸酯、透明质酸钠、水解透明质酸钠、乙酰化透明质酸钠、聚谷氨酸钠、水解小核菌胶、出芽短梗酶多糖、银耳多糖、酸豆籽多糖、1,2-己二醇、天然保湿因子、神经酰胺2、神经酰胺3、胆固醇、磷脂等中的一种或多种。所述保湿剂在所述皮肤外用组合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的1-30％。
所述其他抗炎活性成分的实例包括但不限于马齿苋(PORTULACA OLERACEA)提取物、生物糖胶-1、β-葡聚糖、果聚糖、黄芩(SCUTELLARIA BAICALENSIS)根提取物、欧洲七叶树(AESCULUS HIPPOCASTANUM)提取物、4-叔丁基环己醇、氢化卵磷脂、光果甘草(GLYCYRRHIZA GLABRA)提取物、水解蜂王浆蛋白、谷维素、植物鞘氨醇、五羟黄酮(槲皮素)、姜根提取物迷迭香叶提取物等中的一种或多种。所述抗炎活性成分在所述皮肤外用组合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的0.01-10％。
所述辅料包括例如乳化剂、增稠剂、防腐剂、香料等。
所述乳化剂的实例包括但不限于鲸蜡硬脂醇橄榄油酸酯、山梨坦橄榄油酸酯、聚山梨醇酯-60、聚山梨醇酯-80、甲基葡糖倍半硬脂酸酯、PEG-20甲基葡糖倍半硬脂酸酯、PEG-40氢化蓖麻油、PPG-26-丁醇聚醚-26、PEG-4聚甘油-2硬脂酸酯、PEG-60氢化蓖麻油、硬脂醇聚醚-2、硬脂醇聚醚-21、PPG-13-癸基十四醇聚醚-24、鲸蜡硬脂基葡糖苷、PEG-100硬脂酸酯、甘油硬脂酸酯、甘油硬脂酸酯SE、椰油基葡糖苷、鲸蜡硬脂醇聚醚-25、PEG-40硬脂酸酯、聚甘油-3甲基葡糖二硬脂酸酯、甘油硬脂酸酯柠檬酸酯、聚甘油-10硬脂酸酯、聚甘油-10肉豆蔻酸酯、聚甘油-10二油酸酯、聚甘油-10月桂酸酯、聚甘油-10异硬脂酸酯、聚甘油-10油酸酯、聚甘油-10二异硬脂酸酯、聚甘油-6月桂酸酯、聚甘油-6肉豆蔻酸酯、蔗糖硬脂酸酯、蔗糖多硬脂酸酯等中的一种或多种。所述乳化剂在所述皮肤外用组 合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的0.5-10％。
所述增稠剂的实例包括但不限于卡波姆类、丙烯酸(酯)类及其衍生物、黄原胶、阿拉伯胶、聚乙二醇-14M、聚乙二醇-90M、琥珀酰聚糖、羟乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素等高分子聚合物中的一种或多种。所述增稠剂在所述皮肤外用组合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的0.1-10％。
所述防腐剂的实例包括但不限于羟苯甲酯、羟苯丙酯、苯氧乙醇、苯甲醇、苯乙醇、双(羟甲基)咪唑烷基脲、山梨酸钾、苯甲酸钠、氯苯甘醚、脱氢乙酸钠、辛酰羟肟酸、1,2-己二醇、1,2-戊二醇、对羟基苯乙酮、辛甘醇、甘油辛酸酯、十一碳烯酸甘油酯、山梨坦辛酸酯、乙基己基甘油、牡丹根提取物等中的一种或多种。所述防腐剂在所述皮肤外用组合物中的含量是本领域已知的，例如，其通常占组分(C)总重量的0.01-2％。
本发明的皮肤外用组合物可以通过本领域已知的任何合适的方法制备。例如，使用化妆品领域中常用的溶解槽、乳化锅、分散器、输送泵等设备制备。制备时先将水溶性物质投入水相溶解釜，将油溶性物质投入油相溶解釜，将两个釜的温度加热至约80℃，其中对于易结块的原料，可先用分散器将其预分散。待溶解完成后将油相和水相输送至乳化锅中，均质乳化约5-15分钟。乳化完成后将料体温度降至常温，加入任选的香精、防腐剂等，并视需要调节产物的pH。相关检测指标都合格后方可灌装出货。
以上制备方法可根据剂型要求进行删减或调整。根据需要，可将所述皮肤外用组合物制成膏、霜、乳液、精华液、喷剂、凝胶等各种剂型。
实施例
以下结合实施例，对本发明进行进一步详细说明。但是，应当理解为，这些实施例、对比例仅仅是用于更详细地说明本发明，而不应理解为用于以任何形式限制本发明所附权利要求书的范围。
实施例1：不同物质体系对刺激性接触性皮炎的影响
本实施例基于刺激性接触性皮炎小鼠模型来评价桦树汁原液、浓缩的桦树汁、燕麦仁提取物和/或的抗炎效果。
1.实验动物：ICR小鼠，雄性
2.实验材料：10％十二烷基硫酸钠溶液(SDS)，脱毛膏、桦树汁、燕麦仁提取物、泛醇
3.实验方法：将ICR小鼠按体重随机分组，每组12只，分为正常组、模型组、各配方组。各组小鼠于造模前1天，用脱毛膏去除小鼠腹部约2x2cm区域面积皮肤毛发。其中模型组、各配方组：造模当天，用移液枪吸取10％十二烷基硫酸钠溶液50μL均匀涂抹于小鼠腹部裸露皮肤，连续涂抹5天。各配方组溶液用相同气雾瓶进行喷施，每次每只均匀喷施2下，每天3次，连续2天。正常组小鼠用相同方法去除腹部鼠毛，饲养7天后进行对照。实验第7天，观察各组实验小鼠皮肤状况，并取小鼠血清测定炎症因子IL-1α含量。
各配方如下：
Figure PCTCN2020102862-appb-000001
其中1.2倍、4倍、9倍桦树汁浓缩液是将桦树汁原液经过浓缩而获得的，浓缩工艺为：将购自大兴安岭超越野生浆果开发有限责任公司的新鲜白桦树汁原液输入低温干燥设备，降温至-65℃，抽真空至0.1Pa，浓缩至1.2倍、4倍、9倍。
4.用不同配方体系处理后，小鼠血清炎症因子IL-α含量如下表所示：
  IL-α(pg/ml)
正常组 19.9±0.5
模型组 44.5±2.09
配方1 20.8±1.2
配方2 21.1±0.4
配方3 23.8±1.2
配方4 22.8±1.3
配方5 28.5±0.9
配方6 32.5±1.4
配方7 25.7±1.2
配方8 23.3±1.3
配方9 31.7±1.9
配方10 29.1±1.4
配方11 35.2±2.4
配方12 23.1±1.9
配方13 29.8±1.2
配方14 36.5±1.3
上表结果表明：当燕麦仁提取物、泛醇与桦树汁组合时，能显著地抑制刺激性接触性皮炎小鼠血清中IL-α的表达。且进一步地，与1.2倍浓缩的桦树汁组合表现了更好的功效。
实施例2：不同的化妆品组合物体系对变应性接触性皮炎的影响
1.实验动物：ICR小鼠，雄性
2.实验材料：1％DNFB丙酮橄榄油溶液(4:1)、脱毛膏、桦树汁、尿囊素、红没药醇3.实验方法：将ICR小鼠按体重随机分组，每组12只，分为正常组、模型组、各配方组。各组实验小鼠于造模前1天，用脱毛膏去除小鼠腹部约2x2cm区域面积皮肤毛发。其中模型组、各配方组小鼠于造模当天，吸取100μL含1％DNFB的丙酮橄榄油溶液均匀涂抹于小鼠腹部裸露皮肤，进行致敏和激发建立小鼠变应性接触性皮炎模型。连续涂抹2天，并于第5天在小鼠双耳内外侧耳面均匀涂以1％DNFB丙酮橄榄油溶液20μL进行激发。正常组小鼠腹部及耳部均匀涂以丙酮橄榄油溶液(4:1)对照。
激发后12小时开始用药，各配方组用相同的气雾瓶对实验小鼠双耳内外面进行均匀喷施，每只耳朵内外面各一次，每天3次，连续给药2天。模型组喷以蒸馏水，连续2天，3次/天，以棉棒反复涂擦内外侧耳面5s左右。
各配方如下：
Figure PCTCN2020102862-appb-000002
4.考察指标：
耳厚度指数：激发后12h、48h后分别测定小鼠双耳厚度，取双耳平均值。
耳重量指标：给药2天后，用打孔器分别取各实验小鼠左耳圆片，称重。
炎症指标测定：用药2天后，取小鼠血清，运用ELISA试剂盒检测小鼠耳组织中炎症因子IFN-γ、IL-4和类胰蛋白酶含量，并计算IFN-γ/IL-4。
5.实验结果：
成分(g) 耳厚度 耳重量 IFN-γ/IL-4
正常组 0.16±0.02 13.7±1.1 5.3±0.3
模型组 0.43±0.02 28.9±1.4 2.7±0.3
配方1 0.19±0.01 15.5±0.8 4.8±0.2
配方2 0.18±0.03 16.1±0.7 4.9±0.3
配方3 0.24±0.02 17.7±1.6 4.4±0.3
配方4 0.28±0.03 26.6±2.7 3.2±0.5
配方5 0.25±0.01 20.7±1.5 4.2±0.5
配方6 0.28±0.02 19.6±1.1 3.9±0.1
配方7 0.33±0.03 23.2±0.5 3.5±0.2
配方8 0.36±0.05 22.5±1.7 3.1±0.1
配方9 0.36±0.03 24.7±1.6 3.4±0.3
配方10 0.23±0.01 17.8±1.2 4.4±0.4
配方11 0.30±0.02 19.7±1.6 4.3±0.3
配方12 0.37±0.03 24.9±2.7 3.7±0.5
上述结果表明，桦树汁与尿囊素、红没药醇组合能显著抑制炎症反应，并平衡血清中IFN-γ/IL-4的比值。且进一步地，与1.2倍浓缩的桦树汁组合物表现了更好的功效。
实施例3：桦树汁对肥大细胞脱颗粒的影响
本实施例利用斑马鱼幼鱼过敏模型测试和对比了桦树汁与甘草酸二钾组合时对肥大细胞脱颗粒的影响，从而验证桦树汁与甘草酸二钾在抗炎方面的功效。
实验方法如下。
1.试验动物：斑马鱼。
2.实验步骤如下：收集AB野生型斑马鱼胚胎，在28.5℃培养箱中用E3 buffer培养至5dpf(days post fertilization)，每天换液。随机将5dpf的斑马鱼幼鱼以每孔10尾的数量转入48孔细胞培养板中分组，每组4个复孔，分组情况如下：
模型组：RO水+15μg/ml SP
阳性药组：酮替芬+15μg/ml SP
待测样品组：
成分(g) 配方1 配方2 配方3 配方4 配方5
白桦树汁原液   95   100  
1.2倍浓缩液 95       100
甘草酸二钾 5 5 5    
水     95    
SP(μg/ml) 15 15 15 15 15
对应于上述加入SP诱导脱颗粒各组，另设阴性对照组(不含SP)，每组4个复孔；对应于SP脱颗粒诱导组和不含SP阴性对照组，另设背景对照组(不含斑马鱼幼鱼)，每组2个复孔。吸干各组孔内残余的E3 buffer并加入250μl对应各个组别的溶液，在28.5℃培养箱中避光反应60分钟。60分钟后，取各组上清液200ul于96孔细胞培养板中，再分别加入酶反应底物BAPNA使其浓度达到400μg/ml。将96孔板避光加盖放入28.5℃培养箱中反应2小时，2小时后测量一次全板405nm下的光吸收值，数值大小反映了斑马鱼肥大细胞的类胰蛋白酶释放情况。
斑马鱼幼鱼肥大细胞保护模型功效实验结果记录在下表中。
组别 肥大细胞保护率
Model _
酮替芬 90.63％
配方1 96.10％
配方2 85.58％
配方3 74.58％
配方4 68.10％
配方5 92.50％
上述结果表明，桦树汁与甘草酸二钾组合显著抑制肥大细胞脱颗粒。且进一步地，与1.2倍浓缩的桦树汁组合表现了更好的功效。
实施例4：抗炎面霜组合物
所述面霜组合物的配方如下：
序号 成分 重量％
1 1.2倍浓缩桦树汁 55
2 聚谷氨酸钠 0.1
3 水解透明质酸钠 0.1
4 黄原胶 0.2
5 尿囊素 0.2
6 羟苯甲酯 0.2
7 氢化卵磷脂 0.5
8 泛醇 0.5
9 甜菜碱 3
10 丁二醇 4
11 甘油 6
12 卡波姆 0.2
13 羟苯丙酯 0.1
14 植物甾醇/辛基十二醇月桂酰谷氨酸酯 1
15 微晶蜡 1
16 C10-18脂酸甘油三酯类 2
17 鲸蜡硬酯基葡糖苷、鲸蜡硬脂醇 2
18 鲸蜡硬脂醇 2
19 PEG-100硬脂酸酯、甘油硬脂酸酯 3
20 辛酸/癸酸甘油三酯 4
21 椰油醇-辛酸酯/癸酸酯 5
22 聚二甲基硅氧烷 2
23 氨丁三醇 0.2
24 苯氧乙醇 0.5
25 燕麦仁提取物 7.2
上述面霜组合物如下制备：
1.将原料4用原料11分散均匀；
2.将原料7用原料10加热溶解；
3.将原料1、25投入水相锅，边搅拌边撒入原料12，待原料12号完全溶胀后加入原料2、3、4、5、6、7、8、9、10、11、25，升温至80℃；
4.将原料13、14、15、16、17、18、19、20、21、22投入油相锅，升温至80℃；
5.将水相锅中的原料抽入乳化锅，高速均质5分钟；
6.将油相锅中的原料抽入乳化锅，高速均质5分钟，保温10分钟；
7.边搅拌边降温至50℃，投入原料23和原料24，慢速均质3分钟；
8.边搅拌边降温至40℃；
9.检验合格后出料。
选择39名肌肤类型为敏感性肌肤，且面部有炎症的受试者，分为三组：第一组连续使用所述面霜组合物；第二组使用不含桦树汁的对照产品A(其配方与上表中完全相同，但全部桦树汁被水替代)；第三组使用对照产品B(其配方与上表中完全相同，但全部尿囊素、泛醇、燕麦仁提取物被水替代)。
4周后的结果表明，相对于两组对照产品，所述面霜组合物显著改善了患者面部炎症反应，并且皮肤稳定性增强。
实施例5：抗炎精华液组合物
所述抗炎精华液组合物的配方如下：
序号 成分 重量％
1 2倍浓缩桦树汁 70.0
2 聚谷氨酸钠 0.05
3 黄原胶 0.05
4 红没药醇 4.1
5 羟苯甲酯 0.2
6 PEG-60氢化蓖麻油 0.2
7 水解透明质酸钠 0.2
8 海藻糖 0.5
9 PEG/PPG-17/6共聚物 1
10 燕麦仁提取物 2
11 双丙甘醇 3
12 PEG-8 5
13 甘油 6
14 丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物 0.05
15 卡波姆 0.2
16 甘油三(乙基己酸)酯 0.5
17 聚二甲基硅氧烷 1
18 鲸蜡醇乙基己酸酯 2
19 氨丁三醇 0.14
20 苯氧乙醇 0.4
21 角鲨烷 3.41
上述精华液组合物如下制备：
1.将原料3用原料11分散均匀；
2.将原料1投入乳化锅，边搅拌边撒入原料14和原料15，待原料14和原料15完全溶胀后，加入原料2、3、4、5、6、7、8、9、10、11、12和原料13，边搅拌边升温至80℃，高速均质5分钟，保温10分钟；
3.边搅拌边降温至50℃，加入原料16、17和原料18，高速均质5分钟；
4.边搅拌边降温至50℃，加入原料19和原料20；
5.边搅拌边降温至40℃；
6.检验合格后出料。
在本实施例中，选择39名肌肤类型为敏感性肌肤，且面部有炎症的受试者，分为三组：第一组连续使用所述精华液组合物；第二组使用不含桦树汁的对照产品A(其配方与上表中完全相同，但全部桦树汁被水替代)；第三组使用对照产品B(其配方与上表中完全相同，但全部红没药醇、燕麦仁提取物被水替代)。
4周后的结果表明，相对于两组对照产品，所述精华液组合物显著改善了患者面部炎症反应，并且皮肤稳定性增强。
实施例6：抗炎乳液组合物
所述抗炎乳液组合物的配方如下：
序号 成分 重量％
1 1.2倍浓缩桦树汁 74
2 水解透明质酸钠 0.05
3 甘草酸二钾 4.05
4 黄原胶 0.1
5 羟苯甲酯 0.2
6 聚山梨醇酯-60 0.3
7 PEG-60氢化蓖麻油 0.5
8 甜菜碱 1
9 双丙甘醇 4
10 神经酰胺 4
11 甘油 7.1
12 卡波姆 0.2
13 植物甾醇/辛基十二醇月桂酰谷氨酸酯 1
14 氨丁三醇 0.1
15 PEG/PPG-17/6共聚物 1
16 苯氧乙醇 0.4
17 尿囊素 2
上述抗炎乳液组合物如下制备：
1.将原料4用原料9分散均匀；
2.将原料1投入乳化锅，边搅拌边撒入原料11，待原料11完全溶胀后再投入原料2、3、4、5、6、7、8、9、10、17；
3.边搅拌边升温至80℃，高速均质5分钟，保温10分钟；
4.加入原料12，高速均质5分钟，保温10分钟；
5.边搅拌边降温至60℃，加入原料13；
6.降温至50℃，加入原料14和原料15，慢速均质3分钟；
7.边搅拌边降温至40℃；
8.检验合格后出料。
在本实施例中，选择39名肌肤类型为敏感性肌肤，且面部有炎症的受试者，分为三 组：第一组连续使用所述乳液组合物；第二组使用不含桦树汁的对照产品A(其配方与上表中完全相同，但全部桦树汁被水替代)；第三组使用对照产品B(其配方与上表中完全相同，但全部甘草酸二钾、尿囊素被水替代)。
4周后的结果表明，相对于两组对照产品，所述乳液组合物显著改善了患者面部炎症反应，并且皮肤稳定性增强。
以上实施例的技术方案是本发明优选实施方式，在不脱离本发明原理的前提下还可以进行若干改进和变换，这些改进和变化也应视为在本发明的保护范围内。

Claims (8)

  1. (A)浓缩的桦树汁与(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种的组合在具有抗炎功效的皮肤外用组合物中的用途，其中所述浓缩的桦树汁的浓缩倍数为1.05-8倍，优选1.1-4倍，更优选1.2-2倍。
  2. 权利要求1的用途，其中所述皮肤外用组合物不包含任何外加的水。
  3. 权利要求1或2的用途，其中所述皮肤外用组合物是药物组合物或者化妆品组合物。
  4. 一种具有抗炎功效的皮肤外用组合物，其包含(A)浓缩的桦树汁，其浓缩倍数为1.05-8倍，优选1.1-4倍，更优选1.2-2倍，和(B)选自燕麦仁提取物、泛醇、尿囊素、红没药醇和甘草酸二钾中的一种或多种物质。
  5. 权利要求4的皮肤外用组合物，其中所述组分(A)浓缩的桦树汁的含量为18-98％重量，优选20-95％重量，更优选22-90％重量，最优选30-90％重量，基于所述皮肤外用组合物的总重量。
  6. 权利要求4或5的皮肤外用组合物，所述组分(B)的含量为0.01-10％，优选0.1-6％，更优选0.5-5％，基于所述皮肤外用组合物的总重量。
  7. 权利要求4-6任一项的皮肤外用组合物，其中所述皮肤外用组合物不包含任何外加的水。
  8. 权利要求4-7任一项的皮肤外用组合物，其中所述皮肤外用组合物是药物组合物或者化妆品组合物。
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