WO2021017838A1 - 具有抗湿疹功效的皮肤外用组合物 - Google Patents

具有抗湿疹功效的皮肤外用组合物 Download PDF

Info

Publication number
WO2021017838A1
WO2021017838A1 PCT/CN2020/102232 CN2020102232W WO2021017838A1 WO 2021017838 A1 WO2021017838 A1 WO 2021017838A1 CN 2020102232 W CN2020102232 W CN 2020102232W WO 2021017838 A1 WO2021017838 A1 WO 2021017838A1
Authority
WO
WIPO (PCT)
Prior art keywords
birch
composition
sap
birch sap
eczema
Prior art date
Application number
PCT/CN2020/102232
Other languages
English (en)
French (fr)
Inventor
魏双萍
王莎莎
Original Assignee
浙江养生堂天然药物研究所有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 浙江养生堂天然药物研究所有限公司 filed Critical 浙江养生堂天然药物研究所有限公司
Publication of WO2021017838A1 publication Critical patent/WO2021017838A1/zh

Links

Classifications

    • 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
    • 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
    • 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

Definitions

  • the present invention relates to the use of birch tree sap in preparing an external skin composition with anti-eczema effect, and a skin external composition with anti-eczema effect, which comprises birch tree sap.
  • the external skin composition includes a skin care cosmetic composition or a pharmaceutical composition.
  • 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. It has a great effect on preventing soil erosion, improving the environment, preventing wind and sand. Birch trees are mostly grown in remote mountainous areas with little human intervention and no industrial pollution. Birch sap is the fresh sap from the birch bark being cut or bored through the trunk. It is colorless or light yellow, free of precipitation and impurities, and has a light birch fragrance.
  • Birch sap contains a large amount of sugars, amino acids, vitamins, biotin, cytokinins, trace mineral elements, aromatic oils, betulin, saponin and other compounds, which have good moisturizing and anti-inflammatory functions.
  • Eczema is an inflammatory skin disease with obvious exudative tendency caused by a variety of internal and external factors, accompanied by obvious itching, abnormal skin barrier function, and easy recurrence.
  • moisturizing agents are often used as the basis, and glucocorticoids are the first-line anti-inflammatory and immunosuppressive drugs for eczema.
  • birch tree sap has good anti-inflammatory and skin barrier repair effects, thereby showing significant efficacy in the treatment of eczema.
  • the present invention relates to the use of birch tree sap in the preparation of an external skin composition with anti-eczema effect.
  • the present invention provides an external skin composition with anti-eczema effect, which comprises (A) birch sap.
  • the external skin composition includes a skin care cosmetic composition or a pharmaceutical composition.
  • the birch sap is an aqueous solution with a concentration of more than 30%.
  • the birch sap is a raw liquid.
  • the birch sap is concentrated birch sap, and its concentration ratio is about 1.05-8 times, preferably about 1.1-4 times, more preferably about 1.2-3 times.
  • the birch sap involved in the present invention is obtained 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 birch tree juice has significant moisturizing, barrier repair and anti-inflammatory and soothing effects, thereby inhibiting the inflammatory response of patients with eczema, repairing the skin barrier, and exerting the effect of treating eczema.
  • the specific performance in terms of moisture retention and barrier repair is to promote the expression of aquaporin AQP, tight junction protein, and keratinocyte-seal related protein in epidermal cells, promote the proliferation and differentiation of keratinocytes, promote the production of hyaluronic acid, and strengthen
  • the structure and functionality of the epidermis, dermis, and dermal-epidermal junctions improve the skin barrier and reduce transdermal water loss.
  • the specific performance is significant inhibition of mast cell degranulation, inhibition of inflammatory factors, antithymic stromal lymphopoietin (TSLP), Th2 type cytokine interleukin-4 (IL-4), interleukin-13 (IL-13) ), the production of interleukin-17 (IL-17).
  • TSLP antithymic stromal lymphopoietin
  • IL-4 Th2 type cytokine interleukin-4
  • IL-13 interleukin-13
  • IL-17 interleukin-17
  • the concentration is preferably performed by a low-temperature freeze concentration or membrane concentration process.
  • the commercially available birch sap stock solution is input to a low-temperature drying equipment, the temperature is lowered to -40°C to -70°C, and the vacuum is pumped to 0.1-30 Pa to perform low-temperature vacuum concentration, thereby obtaining concentrated birch sap with different concentration multiples.
  • the present inventors also found that the anti-eczema effect of concentrated birch sap is not in a simple linear relationship with the degree of concentration, but a trend that first increases and then decreases as the concentration ratio increases. Therefore, it is necessary to control the concentration ratio of birch sap.
  • the concentration ratio of birch sap is controlled to be about 1.05-8 times, preferably about 1.1-4 times, more preferably about 1.2-3 times.
  • the skin topical composition contains 18-98%, preferably 20-95%, more preferably 22-90%, most preferably 30-90% of (A) birch sap.
  • the skin external composition of the present invention does not contain any added water, but does not exclude the moisture inherently contained in each component.
  • the external skin composition of the present invention does not contain chelating agents such as EDTA salt, sodium polyphosphate, sodium metaphosphate, and gluconic acid.
  • the external skin composition may optionally include (B) ingredients commonly used in external skin compositions, which are known in the art.
  • components commonly used in skin topical compositions of component (B) include, but are not limited to, vehicles, active ingredients and excipients, etc., and for example, the total content of component (B) is usually about 2-82%, based on the The total weight of the skin topical composition.
  • 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 (B).
  • the active ingredients include, for example, emollients, moisturizers, anti-inflammatory active ingredients, anti-eczema active ingredients and the like.
  • emollient examples include, but are not limited to, olive oil, macadamia nut 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 tree kernel oil, jojoba seed oil, sunflower seed oil, palm tree fruit oil, squalane, ethylhexyl palmitate, isopropyl myristate, hydrogenated polyisobutylene, isotene Hexane, isododecane, diethylhexyl carbonate, dioctyl carbonate, isopropyl lauroyl sarcosine, isononyl isononanoate, hydrogenated polydecene, glycerol tri(ethylhexanoate) , Cetyl alcohol ethyl hexanoate, bis-diethoxy diethylene glycol cyclohexane
  • 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 external skin composition is known in the art, for example, it usually accounts for 1-50% of the total weight of the component (B).
  • 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, dipotassium glycyrrhizinate, portulaca (PORTULACA OLERACEA) extract, oat (AVENA SATIVA) kernel extract (oatyl anthranilic acid), panthenol, allantoin , Biological sugar gum-1, ⁇ -glucan, fructan, SCUTELLARIA BAICALENSIS root extract, Aesculus HIPPOCASTANUM extract, bisabolol, 4-tert-butyl cyclohexanol, nerve Amide 3, hydrogenated lecithin, licorice root (GLYCYRRHIZA GLABRA) extract, hydrolyzed royal jelly protein, oryzanol, phytosphingosine, quercetin (quercetin), 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
  • anti-eczema active ingredients include, but are not limited to, glucocorticoids (including glucocorticoids of all strengths), zinc oxide, calamine, boric acid solution, berberine hydrochloride, ethacridine solution, urea, salicylic acid Acid, calcineurin inhibitor, salicylic acid, lactic acid, tretinoin, tar, vitamin C, calcium gluconate, zinc copper sulfate, etc.
  • the content of the anti-eczema active ingredient in the skin external composition is known in the art.
  • 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 (B).
  • 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 (B).
  • 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 above preparation method can be deleted or adjusted according to the requirements of the dosage form, and the external skin composition of the dosage form of cream, cream, lotion, essence, spray, gel, etc. can be prepared as needed, especially the skin care cosmetic composition.
  • Example 1 The effect of birch sap on the expression of genes related to moisture retention and barrier repair
  • This example investigated the effects of birch sap on cutin transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG and aquaporin AQP3.
  • the experimental method is as follows.
  • Experimental reagents and consumables keratinocytes, 6-well plate, cell culture medium, RNA extraction kit, reverse transcription kit, Trizol lysis solution, etc.
  • Inoculation Inoculate cells into a 6-well plate at a seeding density of 2E5/well, and incubate overnight in an incubator at 37°C and 5% CO 2 ;
  • Liquid preparation prepare birch tree juice of different concentrations, which are 100%, 60%, 30%, 10%, 1.2 times concentrated juice, 2.5 times concentrated juice, and 6 times concentrated juice;
  • RNA is extracted, reverse transcribed to cDNA, and then subjected to fluorescence quantitative PCR detection;
  • 10% birch sap is a mixture of 10% birch sap stock solution and 90% deionized water, and so on. 100% birch sap refers to the original birch sap.
  • the 1.2 times concentrated birch sap is obtained by concentrating the original birch sap.
  • the concentration process is: the fresh birch sap stock purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd. is fed into the low-temperature drying equipment, and the temperature is cooled to -65°C , Evacuate to 0.1Pa and concentrate to 1.2 times, 2.5 times, and 6 times respectively.
  • birch sap especially birch sap at a concentration of more than 30%, can significantly increase the expression of moisturizing and barrier repair related genes, such as cutin transglutaminase TGM1, epidermal tight junction protein (ZO-1 And CLDN1), filaggrin FLG and aquaporin AQP3.
  • the above results also show that the effect of birch sap stock solution is particularly significant, and further, 1.2 and 2.5 times the concentrated birch sap shows better efficacy.
  • Example 2 The effect of birch sap on the expression of proteins related to moisturizing and barrier repair
  • This example investigated the effects of birch sap on cutin transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG and aquaporin AQP3.
  • the experimental method is as follows.
  • Experimental reagents and consumables human primary keratinocytes, 12-well plates, keratinocyte culture medium, ELISA test kits with different indicators, etc.
  • Inoculation Inoculate in a 12-well culture plate at an inoculation density of 2E5/well, cultivate in an incubator at 37°C and 5% CO2, and change the medium every two days;
  • Example 3 Effect of birch sap on the proliferation and differentiation of keratinocytes
  • This example tested and compared the effects of different concentrations of birch sap on the proliferation and differentiation of keratinocytes.
  • the experimental method is as follows.
  • HACAT human immortalized epidermal keratinocytes
  • the above experiment is done in three groups in parallel.
  • the cells come from three culture flasks, and cell counting and experimental operations are performed independently. The results obtained are shown in Table 3 below.
  • Example 4 The effect of birch sap on degranulation of mast cells
  • This example uses a zebrafish juvenile allergy model to test and compare the effects of different concentrations of birch sap on mast cell degranulation, thereby verifying the anti-inflammatory effect of birch sap.
  • the experimental method is as follows.
  • the experimental procedure is as follows: Collect AB wild-type zebrafish embryos, culture them with E3buffer 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:
  • Sample group to be tested 100%, 60%, 30%, 10% birch tree juice, 1.2 times concentrated juice, 2.5 times concentrated juice, 6 times concentrated juice + 15 ⁇ g/ml SP.
  • 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. Absorb the remaining E3buffer in each group of wells and add 250 ⁇ l of the solution corresponding to each group, and react for 60 minutes in the incubator at 28.5°C 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.
  • Example 5 The effect of birch sap on the production of inflammatory factors during eczema
  • DNFB 2,4-dinitrofluorobenzene
  • the experimental method is as follows.
  • mice ICR mice, males.
  • mice are randomly grouped according to their body weight, each with 12 mice, divided into normal group, model group, positive group, and birch juice group.
  • hair removal cream was used to remove the skin and hair of about 2*2cm on the back of the mice.
  • the transparent wide tape was repeatedly applied 8 times to remove the cuticle. Then in the first week, on the 1, 3, 5, and 7 days, all experimental animals were sensitized by injection of dust mite extract.
  • the dust mite extract was injected to induce sensitization; in the 3rd to 6th week of the experiment, the dust mite extract was injected once a week to induce sensitization.
  • Acetone (DNCB) should be diluted with double-distilled water to 0.5% acetone solution, and 0.5% DNCB was fixedly contacted on the back of the mouse every other day in the second week, as described above, once, 100 ⁇ L each time, and every other day from the second week. 70 ⁇ L each time, sensitized for 6 weeks.
  • the medication was started 12 hours after the successful modeling, and birch sap of different concentrations was evenly sprayed on the back of the experimental mice with an aerosol bottle, 3 times a day for 7 consecutive days.
  • the model group was sprayed with distilled water, and the positive group was sprayed with 1% hydrocortisone ointment for 7 consecutive days, 3 times a day.
  • the formula of the anti-eczema cream composition is as follows:
  • the above anti-eczema cream composition is prepared as follows:
  • the formula of the anti-eczema essence composition is as follows:
  • the aforementioned anti-eczema 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 anti-eczema emulsion composition described above is prepared as follows:
  • the anti-eczema emulsion significantly improved the skin condition (p ⁇ 0.05), and further significantly improved on the 21st day (p ⁇ 0.01). This indicates that the anti-eczema emulsion can treat mild to moderate eczema.
  • the formula of the anti-eczema ointment composition is as follows:
  • the above-mentioned anti-eczema ointment composition is prepared as follows:

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Birds (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

涉及桦树汁在制备具有抗湿疹功效的皮肤外用组合物中的用途，以及具有抗湿疹功效的皮肤外用组合物，其包含桦树汁。

Description

具有抗湿疹功效的皮肤外用组合物 技术领域
本发明涉及桦树汁在制备具有抗湿疹功效的皮肤外用组合物中的用途，以及具有抗湿疹功效的皮肤外用组合物，其包含桦树汁。其中，所述皮肤外用组合物包括护肤化妆品组合物或药物组合物。
背景技术
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。其对于防止水土流失、改善环境、防风防沙有极大作用。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。其营养丰富，在摄入人体后经过代谢可以形成对健康有利的因子，从而达到对亚健康人群的保健效果，使其具有良好的营养保健作用，常被用来制作饮料、酒等饮品。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、抗炎等功能。
湿疹是由多种内外因素引起的一种具有明显渗出倾向的炎症性皮肤病，伴有明显瘙痒，皮肤屏障功能异常，易复发。对于湿疹常以润肤剂保湿为基础方案，糖皮质激素为湿疹抗炎、免疫抑制的一线治疗药物。
本发明人发现，桦树汁具有良好的抗炎、修复皮肤屏障的功效，从而在治疗湿疹中显示了显著的疗效。
发明内容
一方面，本发明涉及桦树汁在制备具有抗湿疹功效的皮肤外用组合物中的用途。
另一方面，本发明提供一种具有抗湿疹功效的皮肤外用组合物，其包含(A)桦树汁。
其中，所述皮肤外用组合物包括护肤化妆品组合物或药物组合物。
所述桦树汁为浓度在30％以上的水溶液。在优选的实施方案中，所述桦树汁为原液。在更优选的实施方案中，所述桦树汁为浓缩的桦树汁，其浓缩倍数为约1.05-8倍，优选约1.1-4倍，更优选约1.2-3倍。
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。
本发明人发现，所述桦树汁具有显著的保湿、屏障修复和抗炎舒敏功效，从而抑制湿疹患者的炎症反应、修复皮肤屏障进而发挥治疗湿疹的功效。其中，在保湿和屏障修复方 面具体的表现为能促进表皮细胞中水通道蛋白AQP、紧密连接蛋白、角质胞封相关蛋白的表达，促进角质形成细胞的增殖和分化，促进透明质酸生成，强化表皮、真皮以及真皮-表皮连接处的结构完整和功能性，提升皮肤屏障，减少经皮水分流失。在抗炎方面具体的表现为具有显著的抑制肥大细胞脱颗粒、抑制炎症因子抗胸腺基质淋巴生成素(TSLP)、Th2型细胞因子白介素-4(IL-4)、白介素-13(IL-13)、白介素-17(IL-17)的产生。
在本发明中，用于浓缩桦树汁以获得浓缩的桦树汁的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必要的，在本发明中，控制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1.2-3倍。
所述皮肤外用组合物包含18-98％，优选20-95％，更优选22-90％，最优选30-90％的(A)桦树汁。
在优选的实施方案中，本发明的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，本发明的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(A)桦树汁外，所述皮肤外用组合物可任选地包含(B)皮肤外用组合物中常用的成分，其是本领域已知的。本领域技术人员可根据需要选择其类型和用量。例如，组分(B)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，和例如，组分(B)的总含量通常为约2-82％，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(B)总重量的0.5-20％。
所述活性成分包括例如润肤剂、保湿剂、抗炎活性成分、抗湿疹活性成分等。
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、角鲨烷、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(B)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(B)总重量的1-30％。
所述抗炎活性成分的实例包括但不限于甘草酸二钾、马齿苋(PORTULACA OLERACEA)提取物、燕麦(AVENA SATIVA)仁提取物(燕麦酰基邻氨基苯甲酸)、泛醇、尿囊素、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、红没药醇、4-叔丁基环己醇、神经酰胺3、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(B)总重量的0.01-10％。
所述抗湿疹活性成分的实例包括但不限于糖皮质激素(包含所有强度的糖皮质激素)、氧化锌、炉甘石、硼酸溶液、盐酸小檗碱、依沙吖啶溶液、尿素、水杨酸、钙调神经磷酸酶抑制剂、水杨酸、乳酸、维A酸、焦油、维生素C、葡萄糖酸钙、硫酸锌铜等。所述抗湿疹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。
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(B)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(B)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(B)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，可根据需要制备膏、霜、乳液、精华液、喷剂、凝胶等剂型的皮肤外用组合物，尤其是护肤化妆品组合物。
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：桦树汁对保湿和屏障修复相关基因表达的影响
本实施例考察研究了桦树汁对角质转谷酰胺酶TGM1、表皮紧密连接蛋白(ZO-1和CLDN1)、丝聚蛋白FLG和水通道蛋白AQP3的影响。
实验方法如下。
1.实验仪器：荧光定量PCR仪(Roche)、超净工作台(苏净)、二氧化碳培养箱(Binder)、酶标仪(BIO-TEK)、微量振荡器。
2.实验试剂与耗材：角质形成细胞、6孔板、细胞培养液、RNA提取试剂盒、反转录试剂盒、Trizol裂解液等。
3.基于角质形成细胞的基因表达分析步骤如下：
(1)接种：以2E5/孔的接种密度，接种细胞至6孔板中，在37℃和5％CO 2培养箱中孵育过夜；
(2)配液：制备不同浓度的桦树汁，分别为100％、60％、30％、10％、1.2倍浓缩汁、2.5 倍浓缩汁、6倍浓缩汁；
(3)给药：待6孔板中细胞铺板率达到50％左右时，加入各组别的受试物，每组设4个复孔；
(4)收样：在37℃和5％CO 2培养箱中24小时后，弃掉培养液，每孔加入1mL Trizol，吹打裂解细胞后，收样；
(5)PCR检测：提取RNA，反转录至cDNA后，进行荧光定量PCR检测；
(6)分析：采用2 -△△CT方法进行结果计算，采用T-Test方法进行统计分析。得到的结果如下表1所示。
表1：
Figure PCTCN2020102232-appb-000001
注：*表示与空白对照相比为显著，P值小于0.05；**表示与空白对照相比为极显著，P值小于0.01。
其中，在上表中，10％的桦树汁是10％的桦树汁原液与90％的去离子水的混合物，以此类推。100％桦树汁是指桦树汁原液。1.2倍浓缩的桦树汁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，分别浓缩至1.2倍、2.5倍、6倍。
上表1中的结果表明，桦树汁、尤其是30％以上浓度的桦树汁能显著增加保湿及屏障修复相关基因的表达，如角质转谷酰胺酶TGM1、表皮紧密连接蛋白(ZO-1和CLDN1)、丝聚蛋白FLG和水通道蛋白AQP3。上述结果还表明，桦树汁原液的效果尤其显著，且进一步地，1.2和2.5倍的浓缩桦树汁表现了更好的功效。
实施例2：桦树汁对保湿和屏障修复相关蛋白表达的影响
本实施例考察研究了桦树汁对角质转谷酰胺酶TGM1、表皮紧密连接蛋白(ZO-1和CLDN1)、丝聚蛋白FLG和水通道蛋白AQP3的影响。
实验方法如下。
1.实验仪器：超净工作台(苏净)、洗板机(BIO-RAD)、酶标仪(BIO-TEK)、二氧化碳培养箱(Binder)。
2.实验试剂及耗材：人原代角质形成细胞、12孔板、角质形成细胞培养液、不同指标的ELISA检测试剂盒等。
3.测试步骤如下：
(1)接种：以2E5/孔的接种密度，接种于12孔培养板中，在37℃和5％CO2培养箱中培养，每两天换一次培养基；
(2)给药：制备不同浓度的桦树汁，分别为100％、60％、30％、10％、1.2倍浓缩汁、2.5倍浓缩汁、6倍浓缩汁；待细胞融合再次达60％以上时，加入不同浓度的受试物，每组设6个复孔；
(3)收样：在37℃和5％CO2培养箱中48小时后，弃掉培养液，每孔加入1mL Trizol，吹打裂解细胞后，收样；
(4)检测：按照ELISA试剂盒的测定方法进行指标测定；
(5)分析：采用T-Test方法进行统计分析。得到的结果如下表2所示。
表2
样品 TGM1 ZO-1 CLDN1 FLG AQP3
空白对照 0.29±0.065 0.5±0.0160 0.425±0.122 0.349±0.192 0.4±0.122
100％的桦树汁 1.103±0.203** 1.255±0.151** 1.073±0.140** 1.207±0.231** 1.303±0.145**
60％的桦树汁 0.878±0.182** 1.0±0.183** 0.986±0.111** 0.970±0.089** 1.01±0.109**
30％的桦树汁 0.623±0.103** 0.876±0.075** 0.81±0.05** 0.89±0.011** 0.858±0.059**
10％的桦树汁 0.408±0.208 0.528±0.311 0.511±0.04 0.380±0.347 0.5±0.410
1.2倍浓缩桦树汁 2.104±0.189** 2.349±0.298** 2.564±0.158** 2.454±0.154** 2.506±0.257**
2.5倍浓缩桦树汁 1.858±0.128** 1.949±0.161** 1.964±0.128** 1.819±0.158** 1.994±0.254**
6倍浓缩桦树汁汁 1.453±0.143** 1.673±0.098** 1.455±0.170** 1.455±0.431** 1.652±0.086**
注：*表示与空白对照相比为显著，P值小于0.05；**表示与空白对照相比为极显著，P值小于0.01。
上表2中的结果表明，桦树汁、尤其是30％以上浓度的桦树汁能显著增强保湿和屏障修复相关蛋白的表达，因此具有显著的修复皮肤屏障的功效。上述结果还表明，桦树汁原液的效果尤其显著，且进一步地，1.2和2.5倍的浓缩桦树汁表现了更好的功效。
实施例3：桦树汁对角质形成细胞增殖和分化能力的影响
本实施例测试和对比了不同浓度的桦树汁对角质形成细胞增殖和分化能力的影响。
实验方法如下。
1.细胞：HACAT(人永生化表皮角质细胞)。
2.实验仪器与耗材：96孔板、1ml移液枪、5ml移液枪、1ml枪头、5ml枪头、15ml离心管、细胞计数器、0.22um过滤器、排枪、排枪槽、DMEM细胞培养液、FBS、100×三抗、100×支原体抑制剂、CCK-8试剂
3.实验步骤如下：
(1)将培养的HACAT细胞接种于96孔板，每孔100ul，细胞密度3000个/孔；
(2)放置于37℃、5％C02培养箱中培养，培养24小时；
(3)给药：加含不同浓度的桦树汁培养基100ul；
(4)孵育到72小时时间后，弃去上清液，每孔加入含cck-8 10％的培养基100ul；
(5)37℃孵育2小时，之后酶标仪450nm检测OD值；
以上实验做三组平行。细胞来自三个培养瓶，细胞计数、实验操作均独立进行。得到的结果如下表3所示。
表3
Figure PCTCN2020102232-appb-000002
注：*表示与空白对照相比为显著，P值小于0.05；**表示与空白对照相比为极显著，P值小于0.01。
上表3中的结果表明，30％以上浓度的桦树汁能显著增强角质形成细胞的增殖和分化能力。上述结果还表明，桦树汁原液的效果尤其显著，且进一步地，1.2和2.5倍的浓缩桦树汁表现了更好的功效。
实施例4：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不同浓度的桦树汁对肥大细胞脱颗粒的影响，从而验证桦树汁在抗炎方面的功效。
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E3buffer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：100％、60％、30％、10％的桦树汁、1.2倍浓缩汁、2.5倍浓缩汁、6倍浓缩汁+15μg/ml SP。
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E3buffer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4中。
表4
组别 肥大细胞保护率
Model -
酮替芬 90.63％**
100％的桦树汁 85.58％**
60％的桦树汁 80.37％**
30％的桦树汁 73.07％**
10％的桦树汁 30％*
1.2倍浓缩桦树汁 96.1％**
2.5倍浓缩桦树汁 93.9％**
6倍浓缩桦树汁 87.99％**
注：*表示p<0.05，**表示p<0.01(与模型组比较)；肥大细胞保护率若大于100％则视作100％。
上表4中的结果表明，30％以上浓度的桦树汁具有显著抑制肥大细胞脱颗粒的效果。上述结果还表明，桦树汁原液的效果尤其显著，且进一步地，1.2倍和2.5倍浓缩的桦树汁表现了更好的功效。
实施例5：桦树汁对湿疹过程中炎症因子产生的影响
本实施例利用2,4-二硝基氟苯(DNFB)致敏和激发建立小鼠的湿疹模型，并给予1％氢化可的松软膏作为阳性对照，并进行不同浓度(100％、60％、30％、10％、1.2倍浓缩汁、2.5倍浓缩汁、6倍浓缩汁)的桦树汁对炎症因子Th2(IL-4、13、17)以及TSLP产生的影响，从而验证桦树汁在抗炎方面的功效。
实验方法如下。
1.实验动物：ICR小鼠，雄性。
2.实验材料：0.5％DNFB丙酮溶液、1％氢化可的松软膏、脱毛膏、尘螨提取液。
3.实验步骤如下：将ICR小鼠按体重随机分组，每组12只，分为正常组、模型组、阳性组、桦树汁组。各组实验小鼠于造模前1天，用脱毛膏去除小鼠背部约2*2cm区域面积皮肤毛发。确定小鼠背部实验范围，透明宽胶带反复黏贴8次去除角质层。然后第1周，第1，3，5，7天，所有的实验动物注射尘螨提取液致敏。实验第2周，第10，13天注射尘螨提取液致敏；实验第3～6周，每周注射1次尘螨提取液致敏，同时行丙酮斑贴诱发。丙酮(DNCB)应用双蒸水稀释至0.5％丙酮溶液，分别于第2周隔日在小鼠背部如上所述固定接触0.5％DNCB 1次，每次100μL，从第2周起每隔2日1次，每次70μL，致敏共6周。
造模成功后12小时开始用药，用气雾瓶将不同浓度的桦树汁对实验小鼠背部均匀喷施，每天3次，连续给药7天。模型组喷以蒸馏水，阳性组涂以1％氢化可的松软膏，连续7天，3次/天。
4、考察指标：用药7天后，取小鼠血清，运用ELISA试剂盒检测小鼠血清炎症因子TSLP、Th2(IL-4、13、17)含量。得到的结果如下表5所示。
表5
  IL-4(pg/ml) IL-13(pg/ml) IL-17(pg/ml) TSLP
阳性药物组 30.11±1.48** 16.34±0.53** 40.56±1.96** 45.59±10.11**
100％的桦树汁 35.29±2.03** 20.76±2.89** 45.23±3.56** 51.24±10.56**
60％的桦树汁 38.23±0.37** 24.87±0.99** 48.43±2.48** 59.59±1.22**
30％的桦树汁 40.33±1.02** 26.76±0.58** 54.59±1.34** 65.14±1.47**
10％的桦树汁 52.29±1.47 33.18±1.33 59.46±1.28 88.28±2.21
造模组 55.9±0.49 35.86±2.21 60.23±1.55 89.13±2.54
正常组 20.56±0.31** 13.86±1.46** 32.77±1.46** 39.21±2.31**
1.2倍浓缩桦树汁 31.25±1.24** 18.59±2.31** 42.51±1.25** 48.91±1.61**
2.5倍浓缩桦树汁 36.05±1.46** 21.59±0.67** 46.50±2.11** 52.13±1.64**
6倍浓缩桦树汁 39.11±1.94** 23.38±1.07** 47.99±2.21** 54.32±1.34**
注：*表示p<0.05，**表示p<0.01(与造模组比较)
上表5中的结果表明，30％以上浓度的桦树汁具有显著的抗炎功效。上述结果还表明，桦树汁原液的效果尤其显著，且进一步地，1.2和2.5倍浓缩桦树汁表现了更好的功效。
实施例6：抗湿疹面霜组合物
所述抗湿疹面霜组合物的配方如下：
Figure PCTCN2020102232-appb-000003
Figure PCTCN2020102232-appb-000004
上述抗湿疹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，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。
在本实施例中，选择12名3-15岁轻度湿疹儿童和12名中度湿疹儿童进行为期3周的治疗。其中6轻度和6名中度湿疹儿童使用所述抗湿疹面霜，每日涂抹2-3次，每次100-200g，其余患者使用不含桦树汁的护肤霜(对照产品，其配方与上表中完全相同，但全部桦树汁被水替代)，连续三周，第14天进行疾病程度评分。结果表明，相比于对照产品，所述抗湿疹面霜显著改善皮肤状况(p<0.05)，第21天进一步显著改善(p<0.01)。这表明，所述抗湿疹面霜可治疗轻至中度湿疹。
实施例7：抗湿疹精华液组合物
所述抗湿疹精华液组合物的配方如下：
Figure PCTCN2020102232-appb-000005
Figure PCTCN2020102232-appb-000006
上述抗湿疹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12名3-15岁轻度湿疹儿童和12名中度湿疹儿童进行为期3周的治疗。其中6轻度和6名中度湿疹儿童使用所述抗湿疹精华液，每日涂抹2-3次，每次100-200g，其余患者使用不含桦树汁的精华液(对照产品，其配方与上表中完全相同，但全部桦树汁被水替代)，连续三周，第14天进行疾病程度评分。结果表明，相比于对照产品，所述抗湿疹精华液显著改善皮肤状况(p<0.05)，第21天进一步显著改善(p<0.01)。这表明，所述抗湿疹精华液可治疗轻至中度湿疹。
实施例8抗湿疹乳液组合物
所述抗湿疹精乳液组合物的配方如下：
Figure PCTCN2020102232-appb-000007
上述抗湿疹乳液组合物如下制备：
1.将原料5用原料10分散均匀。
2.将原料1投入乳化锅，边搅拌边撒入原料12，待原料12完全溶胀后再投入原料2、3、4、5、6、7、8、9、10、11。
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13和原料14，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15。
6.降温至50℃，加入原料16和原料17，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12名3-15岁轻度湿疹儿童和12名中度湿疹儿童进行为期3周的治疗。其中6轻度和6名中度湿疹儿童使用所述抗湿疹乳液，每日涂抹2-3次，每次100-200g，其余患者使用不含桦树汁的乳液(对照产品，其配方与上表中完全相同，但全部浓缩桦树汁被桦树汁原汁替代)，连续三周，第14天进行疾病程度评分。结果表明，相对于对照产品，所述抗湿疹乳液显著改善皮肤状况(p<0.05)，第21天进一步显著改善(p<0.01)。这表明，所述抗湿疹乳液可治疗轻至中度湿疹。
实施例9：抗湿疹膏剂组合物
所述抗湿疹膏剂组合物的配方如下：
序号 成分 重量％
1 1.2倍浓缩桦树汁 51
2 水解透明质酸钠 3.10
3 黄原胶 0.20
4 尿囊素 0.20
5 醋酸地塞米松 0.02
6 泛醇 0.50
7 甜菜碱 3
8 甘油 10
9 白矿脂 5
10 C12-15醇苯甲酸酯 5
11 液体石蜡 4
12 鲸蜡硬脂醇 3
13 硬脂酸 3
14 甘油硬脂酸酯/PEG-100硬脂酸酯 2.50
15 山梨坦硬脂酸酯 2
16 聚山梨醇酯-60 1
17 聚二甲基硅氧烷 2
18 苯氧乙醇 0.50
19 乙醇 4
上述抗湿疹膏剂组合物如下制备：
1.将原料3用原料8分散均匀。
2.将原料5用原料19溶解。
3.将原料1投入水相锅，边搅拌边加入原料2、3、4、6、7、8、升温至80℃。
4.将原料9、10、11、12、13、14、15、16、17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5、19和原料18，慢速均质3分钟。
8.边搅拌边降温至40℃。
9.检验合格后出料。
在本实施例中，选择12名3-15岁轻度湿疹儿童和12名中度湿疹儿童进行为期2周的治疗。其中6轻度和6名中度湿疹儿童使用所述抗湿疹膏剂，每日涂抹2次，其余患者使用不含桦树汁的膏剂(对照产品，其配方与上表中完全相同，但全部桦树汁被水替代)，连续三周，第7天进行疾病程度评分。结果表明，相对于对照产品，所述抗湿疹膏剂显著改善皮肤状况(p<0.05)，第14天进一步显著改善(p<0.01)。这表明，所述抗湿疹膏剂可治疗轻至中度湿疹。
以上所述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 (13)

  1. 桦树汁在制备具有抗湿疹功效的皮肤外用组合物中的用途。
  2. 权利要求1所述的用途，其中所述桦树汁为浓度在30％以上的水溶液。
  3. 权利要求1所述的用途，其中所述桦树汁为桦树汁原液。
  4. 权利要求1所述的用途，其中所述桦树汁为浓缩的桦树汁，其浓缩倍数为1.05-8倍，优选1.1-4倍，更优选1.2-3倍。
  5. 权利要求1、3和4任一项所述的用途，其中所述皮肤外用组合物不包含任何外加的水。
  6. 权利要求1-5任一项所述的用途，其中所述皮肤外用组合物为护肤化妆品组合物或药物组合物。
  7. 一种具有抗湿疹功效的皮肤外用组合物，其包含桦树汁。
  8. 权利要求7所述的皮肤外用组合物，其中所述桦树汁为浓度在30％以上的水溶液。
  9. 权利要求7所述的皮肤外用组合物，其中所述桦树汁为桦树汁原液。
  10. 权利要求7所述的皮肤外用组合物，其中所述桦树汁为浓缩的桦树汁，其浓缩倍数为1.05-8倍，优选1.1-4倍，更优选1.2-3倍。
  11. 权利要求7-10任一项所述的皮肤外用组合物，其中所述皮肤外用组合物包含18-98％，优选20-95％，更优选22-90％，最优选30-90％的桦树汁。
  12. 权利要求7和9-11任一项所述的皮肤外用组合物，其不包含任何外加的水。
  13. 权利要求7-12任一项所述的皮肤外用组合物，其为护肤化妆品组合物或药物组合物。
PCT/CN2020/102232 2019-07-30 2020-07-16 具有抗湿疹功效的皮肤外用组合物 WO2021017838A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201910694273.3A CN110731975A (zh) 2019-07-30 2019-07-30 具有抗湿疹功效的皮肤外用组合物
CN201910694273.3 2019-07-30

Publications (1)

Publication Number Publication Date
WO2021017838A1 true WO2021017838A1 (zh) 2021-02-04

Family

ID=69267648

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/102232 WO2021017838A1 (zh) 2019-07-30 2020-07-16 具有抗湿疹功效的皮肤外用组合物

Country Status (2)

Country Link
CN (1) CN110731975A (zh)
WO (1) WO2021017838A1 (zh)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110731976B (zh) * 2019-07-30 2024-02-06 浙江养生堂天然药物研究所有限公司 防脱生发组合物
CN110731925A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 美白化妆品组合物
CN110731975A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 具有抗湿疹功效的皮肤外用组合物
CN110876760B (zh) * 2019-11-28 2022-09-30 浙江养生堂天然药物研究所有限公司 具有促进伤口愈合和/或疤痕修复功效的皮肤外用组合物
CN114632136B (zh) * 2020-12-15 2024-09-27 浙江养生堂天然药物研究所有限公司 具有增强的抗湿疹功效的皮肤外用组合物
CN113041271B (zh) * 2021-04-14 2022-12-27 浙江养生堂天然药物研究所有限公司 具有预防和抗过敏功效的组合物
CN115137833A (zh) * 2022-07-14 2022-10-04 广东省人民医院 一种对中药外用膏防腐体系的研究技术

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2929849A1 (fr) * 2008-04-11 2009-10-16 Brigitte Madeleine Michele Martin Procede de fabrication d'huiles cosmetiques ou de pharmacie destinees a faciliter le massage et a etre utilisee chaude (modelage corporels de bien-etre)
CN110731975A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 具有抗湿疹功效的皮肤外用组合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2929849A1 (fr) * 2008-04-11 2009-10-16 Brigitte Madeleine Michele Martin Procede de fabrication d'huiles cosmetiques ou de pharmacie destinees a faciliter le massage et a etre utilisee chaude (modelage corporels de bien-etre)
CN110731975A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 具有抗湿疹功效的皮肤外用组合物

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Local Food Safety Standards: Silver Birch (Betula Pendula) Sap Concentrate", LOCAL STANDARDS IN HEILONGJIANG, vol. DBS23, 19 December 2018 (2018-12-19), pages 1 - 8, XP009525688 *
JIANG, DESEN ET AL: "Study on Concentration of Birch Sap", JOURNAL OF JILIN FORESTRY UNIVERSITY, vol. 5, no. 2, 30 April 1989 (1989-04-30), pages 63 - 70, XP009525687, ISSN: 1004-6992 *
JIANG, ZHONGHAI: "Study on the Birch Juice in Heilongjiang", SCIENCE AND TECHNOLOGY OF FOOD INDUSTRY, vol. 23, no. 10, 31 October 2002 (2002-10-31), pages 62 - 63, XP009525685, DOI: 10.13386/j.issn1002-0306.2002.10.024 *
SHENG YAN, WU ZEZHU: "Research Progress in Nutrient Composition Function and Utilization of Birch Sap", FARM PRODUCTS PROCESSING, no. 7, 31 July 2017 (2017-07-31), pages 49 - 52, XP055776281, ISSN: 1671-9646, DOI: 10.16693/j.cnki.1671-9646 *

Also Published As

Publication number Publication date
CN110731975A (zh) 2020-01-31

Similar Documents

Publication Publication Date Title
WO2021017838A1 (zh) 具有抗湿疹功效的皮肤外用组合物
WO2021017844A1 (zh) 具有增强的抗湿疹功效的皮肤外用组合物
WO2021017846A1 (zh) 增强的抗衰老化妆品组合物
JP7320666B2 (ja) 強化された抗炎症有効性を有する皮膚局所用組成物
WO2021017833A1 (zh) 抗衰老化妆品组合物
WO2021031750A1 (zh) 混合的桦树汁及其在护肤化妆品组合物中的应用
WO2021017835A1 (zh) 增强的美白化妆品组合物
WO2021017834A1 (zh) 具有抗炎功效的皮肤外用组合物
CN110731923A (zh) 增强的保湿化妆品组合物
CN110731976B (zh) 防脱生发组合物
WO2021017877A1 (zh) 美白化妆品组合物
WO2021017912A1 (zh) 保湿化妆品组合物
CN108670878A (zh) 抗皮肤过敏的化妆品组合物
CN114632049B (zh) 一种防脱生发组合物
CN112656731A (zh) 一种具有修红功效的组合物及其制备方法和应用
CN114632136B (zh) 具有增强的抗湿疹功效的皮肤外用组合物
CN114948814B (zh) 紫珠果提取物在制备抑制组胺生成的护肤品中的应用
WO2021017448A1 (zh) 具有止痒功效的皮肤外用组合物
CN112842976B (zh) 酵母菌发酵的桦树汁及其在抗炎化妆品组合物中的应用
CN115607476A (zh) 一种具有保湿抗氧化功效的组合物及其应用
CN110215417B (zh) 一种柔润保湿乳及其制备方法
CN113456547B (zh) 一种舒敏抗炎功效的护肤组合物及其应用
CN114983875B (zh) 一种舒敏抗炎护肤组合物及其应用
CN109276527A (zh) 一种提高皮肤弹性的植物提取物及其在化妆品的应用
JP3822517B2 (ja) 皮膚外用剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20847559

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20847559

Country of ref document: EP

Kind code of ref document: A1