WO2021017448A1 - 具有止痒功效的皮肤外用组合物 - Google Patents

具有止痒功效的皮肤外用组合物 Download PDF

Info

Publication number
WO2021017448A1
WO2021017448A1 PCT/CN2020/073125 CN2020073125W WO2021017448A1 WO 2021017448 A1 WO2021017448 A1 WO 2021017448A1 CN 2020073125 W CN2020073125 W CN 2020073125W WO 2021017448 A1 WO2021017448 A1 WO 2021017448A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
skin
birch sap
betaine
combination
Prior art date
Application number
PCT/CN2020/073125
Other languages
English (en)
French (fr)
Inventor
赵仕芝
宁新娟
王莎莎
Original Assignee
养生堂（安吉）化妆品有限公司
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 养生堂（安吉）化妆品有限公司 filed Critical 养生堂（安吉）化妆品有限公司
Priority to EP20848631.6A priority Critical patent/EP4005553A4/en
Priority to KR1020227002439A priority patent/KR20220025833A/ko
Priority to US17/619,488 priority patent/US20220370534A1/en
Publication of WO2021017448A1 publication Critical patent/WO2021017448A1/zh

Links

Classifications

    • 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
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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)
    • A61K36/49—Fagaceae (Beech family), e.g. oak or chestnut
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • 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
    • 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
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • 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
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous
    • 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
    • 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
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • 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
    • A61K2800/70—Biological properties of the composition as a whole

Definitions

  • the present invention relates to an external skin composition with antipruritic effect, which comprises a combination of (A) birch sap and (B) betaine, the skin external composition does not contain water added as a separate component.
  • the mechanism of skin pruritus is not completely clear. Studies in recent years have shown that the occurrence of skin pruritus may be related to the participation of several mediators: such as histamine, serotonin, neuropeptides, cytokines, etc. Among them, histamine mainly exists in the metachromatic granules in mast cells. The blood vessels of the skin have H 1 and H 2 receptors. The vasodilatation and increased vascular permeability caused by histamine are the two receptors. result. Histamine causes itching in the epidermis or basement membrane, while being released into the dermis causes pain and edema. Therefore, inhibiting the activation and degranulation of mast cells and reducing the release of histamine can alleviate skin itching.
  • mediators such as histamine, serotonin, neuropeptides, cytokines, etc.
  • histamine mainly exists in the metachromatic granules in mast cells.
  • the blood vessels of the skin have H 1 and H
  • the present invention provides an external skin composition, especially a cosmetic composition, which can fundamentally inhibit the release of the itching mediator-histamine, thereby effectively alleviating the symptoms of itching.
  • the composition can be applied to different cosmetic formulations, and has the advantages of convenient use, easy absorption, long-term use, and good anti-itching effect.
  • the present invention relates to the use of a combination of birch sap and betaine in an external skin composition with anti-itching effect, wherein the external skin composition does not contain water added as a separate component.
  • the present invention provides a skin external composition with antipruritic effect, which comprises a combination of (A) birch sap and (B) betaine, wherein the skin external composition does not contain added as a separate component Of water.
  • the external skin composition includes, but is not limited to, pharmaceutical compositions and cosmetic compositions, especially cosmetic compositions, more especially skin care cosmetic compositions.
  • the external skin composition of the present invention can inhibit the release of histamine from mast cells, and therefore has a good effect of relieving and inhibiting skin itching.
  • the skin topical composition of the present invention provides significantly improved antihistamine efficacy, which indicates that the combination of birch sap and betaine is effective Synergistic and synergistic effects are produced in the anhydrous system.
  • the external skin composition of the present invention does not contain any additional water, but does not exclude the water inherent in the birch sap used and the small or trace amounts of water unavoidably introduced in other ingredients.
  • the external skin composition of the present invention 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 birches involved in the present invention belong to the genus Betula, Betula alba, and can come from three species: Betula alba, Betula Pendula and Asian white birch (Betula platyphylla).
  • the component (A) birch sap is also called birch sap and white birch sap.
  • Birch sap is rich in nutrients, including sugars, fatty acids, amino acids, mineral elements, etc.
  • the collection time starts from when the snow starts to melt and ends when the trees are laid out. The collection time is 40-60 cm above the ground. Small holes are drilled in the birch trunk, and a liquid guiding device is placed. After the birch sap is collected and filtered, it is sterilized by conventional methods to obtain a juice that is free of impurities, no precipitation, colorless, transparent and nutritious.
  • the birch sap can be purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd.
  • the birch sap can be in the form of a raw birch sap or a concentrated birch sap, which is called a concentrated birch sap.
  • the concentration ratio is 1.05-8 times, preferably 1.1-4 times, and more preferably 1.2-2 times the concentration of concentrated birch sap and betaine.
  • the combination shows a better effect of relieving skin itching.
  • the method for concentrating the concentrated birch sap is as follows: input the fresh birch sap stock liquid into the reverse osmosis circulation device, the operating pressure is controlled at 0.5-5 bar, the operating temperature is controlled at 20-35°C, then the temperature is reduced to -65°C, and vacuum is applied. To 0.1Pa, circulate until the birch sap is respectively concentrated to 1.1 times, 1.2 times, 1.5 times, 2 times, 4 times, 8 times, etc.
  • the external skin composition of the present invention may contain 5-99.9% by weight, preferably 20-95% by weight, more preferably 35-90% by weight of birch tree sap, based on the total weight of the skin external composition.
  • the component (B) betaine also known as trimethylglycine, is easy to interact with water and has excellent moisturizing properties.
  • the betaine used in the present invention can be obtained from suppliers such as Kneo Trading (Shanghai) Co., Ltd.
  • the external skin composition of the present invention may contain 0.01-20% by weight, preferably 0.1-15% by weight, more preferably 1-10% by weight of betaine, based on the total weight of the skin external composition.
  • the skin external composition of the present invention may optionally contain (C) commonly used ingredients in pharmaceutical or cosmetic compositions, including vehicle, surface active Agents, active ingredients for skin care, active ingredients for medicines, and auxiliary materials, and other ingredients known in the art, and their type and amount can be selected according to specific needs.
  • C commonly used ingredients in pharmaceutical or cosmetic compositions, including vehicle, surface active Agents, active ingredients for skin care, active ingredients for medicines, and auxiliary materials, and other ingredients known in the art, and their type and amount can be selected according to specific needs.
  • the content of component (C) is 0-65% by weight, based on the total weight of the skin external composition.
  • the vehicle is known in the art and includes but is not limited to diluent, dispersant or carrier, etc. Examples thereof include but are not limited to ethanol, butylene glycol, dipropylene glycol and the like. Those skilled in the art can select the type and dosage according to needs. Generally, in the external skin composition of the present invention, the vehicle accounts for 0.5-20% of the total weight of the component (C).
  • the surfactant is any type of surfactant commonly used in medicines or cosmetics, which is used to reduce the surface tension of the interface to achieve the purpose of cleaning, emulsifying and stabilizing the system.
  • the surfactant include, but are not limited to, fatty acid soaps (such as sodium laurate, sodium palmitate, etc.), higher alkyl sulfates (such as sodium lauryl sulfate, etc.), N-acyl sarcosine (such as lauroyl sarcosine) Sodium sulfonate, etc.), higher fatty acid amide sulfonates (such as sodium lauryl methyl taurate, etc.), alkylbenzene sulfonates, higher fatty acid ester sulfates (such as hardened coconut oil fatty acid sodium glycerol sulfate, etc.), N-acylglutamate, lauryl dimethylaminoacetic acid betaine, alkyl betaine, amido betaine, sorb
  • the skin care active ingredients are known in the art, and include, but are not limited to, moisturizers, skin conditioners, emollients, and the like.
  • humectant examples include, but are not limited to, glycerin, trehalose, sucrose, panthenol, propylene glycol, 1,2-pentanediol, mannitol, glycerol-26, rhamnose, raffinose, erythritol , Polyethylene glycol-8, polyethylene glycol-32, methylglucitol-10, methylglucitol-20, PEG/PPG-17/6 copolymer, sodium polyglutamate , Xylitol, urea, hydrolyzed sclerotin gum, sodium polyglutamate, glycerol glucoside, PPG-10 methyl glucoside, sprouting enzyme polysaccharide, tremella polysaccharide, PPG-20 methyl glucoside, etc.
  • the moisturizer accounts for 1-30% of the total weight of the component (C).
  • emollients include, but are not limited to, triglyceride (ethylhexanoate), caprylic/capric triglyceride, grape seed oil, white flower seed oil, shea butter, cetyl alcohol, polydimethyl Siloxane, pentaerythritol tetra(ethylhexanoate) ester, olive oil, avocado oil, corn oil, dioctyl carbonate, humosalate, squalane, stearyl alcohol, isopropyl myristate, One or more of myristyl alcohol, hydrogenated polydecene, palm tree oil, sunflower seed oil, isohexadecane, jojoba oil, lanolin, paraffin, microcrystalline wax, and beeswax.
  • the emollient accounts for 0.01-50% of the total weight of the component (C).
  • the skin conditioner can be used for moisturizing, anti-wrinkle, freckle, acne, oil control and other effects.
  • examples thereof include, but are not limited to, phytosterol/octyldodecanol lauroyl glutamate, turmeric root extract, ceramide 2, ceramide 3, hydrolyzed sodium hyaluronate, acetyl sphingosine, cholesterol, Qu Acid, ascorbic acid, ascorbyl glucoside, allantoin, birch bark extract, hydrogenated lecithin, arbutin, tranexamic acid, nicotinamide, acetyl sphingosine, resveratrol, palm tree bark extract Compounds, Coleus forskohlii Root Extract, Bisabolol, Ascorbyl Tetraisopalmitate, Pepper Seed Extract, Ubiquinone, Pyridoxine Dipalmitate, Pyridoxine Dicaprylate, Retinol One or more of palmitate, to
  • the pharmaceutical active ingredients are those ingredients known in the art for relieving skin itching. Examples thereof include, but are not limited to, Sophora flavescens extract, paeonol, linalool, cineole, borneol, sulfur, cicada slough, Cnidium monnieri extract, Kochia scoparia extract, Bistort extract, Perilla extract, Calamine, Sapindus saponin, Portulaca oleracea extract, ammonium glycyrrhizinate, etc. Generally, in the external skin composition of the present invention, the pharmaceutically active ingredient accounts for 0.01-80% of the total weight of the component (C).
  • the auxiliary materials include, but are not limited to, emulsifiers, thickeners, preservatives, perfumes, pH regulators and the like.
  • the emulsifier examples include, but are not limited to, sorbitan oleate, steareth-21, PEG-60 hydrogenated castor oil, glyceryl stearate/PEG-100 stearate, PPG-13- Decyltetradeceth-24, cetearyl glucoside, polyglyceryl-10 myristate, cetearyl glucoside, polyglyceryl-10 stearate, polyglyceryl-10 dioil One or more of acid esters.
  • the emulsifier accounts for 0.01-10% of the total weight of the component (C).
  • thickener examples include, but are not limited to, hydroxyethyl cellulose, hydroxypropyl cellulose, carbomer, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinyl One or more of polysaccharides, acrylics/C10-30 alkanol acrylate cross-linked polymers, etc. Those skilled in the art can specifically select its type and dosage according to needs.
  • the preservative examples include, but are not limited to, one or more of methylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenethyl alcohol, potassium sorbate, sodium benzoate, chloropheneglycol, etc.
  • Other antiseptic synergists such as pentanediol, hexanediol, octylene glycol, p-hydroxyacetophenone, etc.
  • the preservative accounts for 0.01-10% of the total weight of the component (C).
  • pH adjusting agent examples include, but are not limited to, one or more of citric acid, sodium citrate, arginine, triethanolamine and the like. Those skilled in the art can select the type and dosage according to specific needs.
  • the preparation of the skin external composition of the present invention can be prepared by any suitable method known in the art.
  • it can be prepared using containers such as dissolving tanks, emulsifying pots, dispersers, and delivery pumps commonly used in the art.
  • the disperser can be used first Pre-disperse it. 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 is lowered to normal temperature, flavors, preservatives, etc. are optionally added, and the pH of the product is adjusted as needed.
  • the products can be filled and shipped only after the relevant test indicators are qualified.
  • compositions or cosmetic compositions in various dosage forms such as liquids, emulsions, creams, creams or gels can be prepared according to needs, wherein the cosmetic compositions can be lotions, sprays, emulsions, essences, BB creams, sunscreens, etc. various types.
  • the preparation process of the above formula is as follows: heat birch sap, concentrated birch sap or water to 80°C, then add betaine, stir evenly and set aside.
  • the obtained samples are all colorless and transparent solutions.
  • Example 2 Effect of experimental group and control group on the release of histamine from RBL-2H3 cells
  • Compound 48/80 (a polymer produced by the condensation of N-methyl-p-methoxyphenethylamine and formaldehyde) is a tool drug that causes degranulation of mast cells. Its mechanism is to act on the mast cell membrane and cause intracellular The increase in calcium ions changes the amount of the second messenger cAMP and cGMP, causing mast cells to degranulate and release histamine.
  • the cell line RBL-2H3 was provided by the Animal Center of Zhejiang Academy of Medical Sciences; the test samples included the above seven sample combinations, and the reagents included fetal bovine serum, table salt, compound 48/80, and histamine Elisa kit.
  • Example 3 The effect of the experimental group and the control group on the release of interleukin-4 (IL-4) from mast cells
  • the specific antigen is cross-linked with the IgE antibody attached to the cell membrane, which leads to cell activation and rapid secretion of inflammatory mediators (histamine, IL-4, IL-13, etc.) related to the particles.
  • inflammatory mediators histamine, IL-4, IL-13, etc.
  • the degranulation of mast cells can be caused by non-specific triggers such as anti-IgE and compound 48/80.
  • non-specific triggers such as anti-IgE and compound 48/80.
  • compound 48/80 was used to stimulate the degranulation of mast cells to release IL-4, an inflammatory mediator, to investigate the protective effect of the tested samples on mast cell allergic reactions.
  • Mast cells were provided by the Animal Center of Zhejiang Academy of Medical Sciences.
  • the reagents include fetal bovine serum, RPM1640 medium, table salt, compound 48/80, sodium cromoglycate, and Elisa (Interleukin-4) kit.
  • the test samples include the control group, the model group, the positive drug (cromolyn sodium) group and the above 7 groups of samples A-E.
  • each sample was prepared with RPMI1640 medium, and each group of samples had 8 multiple holes. Inoculate mast cells into a 96-well culture plate at a density of 5*10 6 /mL, 90 ⁇ L per well, add 10 ⁇ L/well of the corresponding sample; place in a 5% CO 2 incubator at 37°C, and take it out after 4 hours ; Then, except for the control group, add stimulus 48/80 (final concentration 20mg/L) to the other groups, continue to incubate in an incubator at 37°C for 2 hours, and then centrifuge at 1500rpm for 5 minutes, and take the supernatant. Interleukin-4 Elisa kit was used to detect the content of IL-4 in the supernatant.
  • This embodiment provides a spray composition with antipruritic effect, and its formula is as follows:
  • the above spray composition is prepared as follows:
  • Use effect test select 30 elderly patients with pruritus skin over the age of 40, regardless of male or female, only pruritus but no primary skin lesions at the onset. After body cleansing every morning and evening, apply the above spray composition to the itchy area. Before the composition is used and after 4 weeks of use, the self-evaluation is performed on the pruritus. According to the degree of improvement, it is divided into obvious improvement, relatively obvious improvement, certain improvement, no obvious improvement, and no improvement at all. It was found that 27 patients (90%) experienced significant improvement in the degree of itching after using the product, while the other 3 patients also improved to varying degrees. It shows that the spray composition has excellent antipruritic effect.
  • This embodiment provides an emulsion composition with antipruritic effect, and its formula is as follows:
  • the above emulsion composition is prepared as follows:
  • Water phase birch juice, glycerin, betaine, panthenol, allantoin, hydrolyzed sodium hyaluronate, pentanediol, xanthan gum, carbomer, and methyl paraben are mixed and heated to 80°C, Stir and dissolve evenly;
  • Oil phase cetyl alcohol, glyceryl stearate/PEG-100 stearate, caprylic/capric triglyceride, triglyceride (ethylhexanoic acid), shea butter. Heat the above raw materials to 80°C, stir and dissolve evenly;
  • Use effect test select 30 elderly patients with pruritus skin over the age of 40, regardless of male or female, only pruritus but no primary skin lesions at the onset. After body cleansing every morning and evening, the above lotion composition is applied to the itchy area. Before the composition is used and after 4 weeks of use, the self-evaluation is performed on the pruritus. According to the degree of improvement, it is divided into obvious improvement, relatively obvious improvement, certain improvement, no obvious improvement, and no improvement at all. The results showed that 28 patients (93.3%) experienced significant improvement in the degree of itching after using the product, while the other 2 patients also improved to varying degrees. It shows that the emulsion composition has excellent antipruritic effect.
  • This embodiment provides a body milk composition with antipruritic effect, and its formula is as follows:
  • the above body milk composition is prepared as follows:
  • Water phase birch sap, glycerin, betaine, panthenol, allantoin, hydrolyzed sodium hyaluronate, dipropylene glycol, trehalose, hydrogenated lecithin, xanthan gum, carbomer, acrylic acid (ester ) Class/C10-30 Alkanol Acrylate Crosslinked Polymer and Methyl Paraben are mixed and heated to 80°C, stirred and dissolved evenly;
  • Oil phase glyceryl stearate/PEG-100 stearate, caprylic acid/capric triglyceride, polymethylsilsesquioxane, myristyl alcohol, beeswax, stearyl alcohol, stearic acid, Shea butter, polydimethylsiloxane. Heat the above raw materials to 80°C, stir and dissolve evenly;
  • Use effect test select 30 elderly patients with pruritus skin over the age of 40, regardless of male or female, only pruritus but no primary skin lesions at the onset. After body cleansing every morning and evening, the above body milk composition is applied to the itchy area. Before the composition is used and after 4 weeks of use, the self-evaluation is performed on the pruritus. According to the degree of improvement, it is divided into obvious improvement, relatively obvious improvement, certain improvement, no obvious improvement, and no improvement at all. The results found that 29 patients (96.7%) had a significant improvement in the degree of itching after using the product, while the other patient also had a significant improvement. It shows that the body milk composition has excellent antipruritic effect.
  • This embodiment provides a cream composition with antipruritic effect, and its formula is as follows:
  • the above cream composition is prepared as follows:
  • Water phase birch sap, betaine, glycerin, panthenol, allantoin, hydrolyzed sodium hyaluronate, glycerol-26, xanthan gum, carbomer, methyl paraben;
  • Oil phase cetyl alcohol, glyceryl caprylate/caprate, pentaerythritol tetra(ethylhexanoate) ester, glyceryl stearate/PEG-100 stearate, shea butter, polydimethyl Siloxane, propyl paraben. Heat the above raw materials to 80°C, stir and dissolve evenly;
  • Use effect test select 30 elderly patients with pruritus skin over the age of 40, regardless of male or female, only pruritus but no primary skin lesions at the onset. After cleansing the body every morning and evening, apply the cream composition to the itchy area. Before the composition is used and after 4 weeks of use, the self-evaluation is performed on the pruritus. According to the degree of improvement, it is divided into obvious improvement, relatively obvious improvement, certain improvement, no obvious improvement, and no improvement at all. The results found that 28 patients (93.3%) had a significant improvement in the degree of itching after using the product, while the other 2 patients also had a significant improvement. It shows that the cream composition has excellent antipruritic effect.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Birds (AREA)
  • Medical Informatics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

一种具有止痒功效的皮肤外用组合物，其包含（A）桦树汁和（B）甜菜碱，所述组合物不包含作为单独组分添加的水。所述皮肤外用组合物为药物组合物或化妆品组合物。

Description

具有止痒功效的皮肤外用组合物 技术领域
本发明涉及一种具有止痒功效的皮肤外用组合物，其包含(A)桦树汁和(B)甜菜碱的组合，所述皮肤外用组合物不包含作为单独组分添加的水。
背景技术
随着年龄的增加，人的皮脂腺功能逐渐减退，皮肤保湿能力开始下降，在秋冬季到来的时候，许多人皮肤会出现瘙痒现象。此外，湿疹、银屑病、皮炎、皮肤干燥症等多种皮肤疾病也都伴随有瘙痒症状，这种症状严重影响患者的身体健康和生活质量。患者若过度抓挠，还会导致患处布满抓痕，影响皮肤美观，甚至引起皮肤感染或溃烂。因此，开发一种能够有效缓解瘙痒症状，又可长期使用的皮肤外用产品、尤其是可长期使用的化妆品是非常必要的。
皮肤瘙痒的发生机制目前并未完全明确，近几年的研究表明，皮肤瘙痒的发生可能与几种介质的参与有关：如组胺、5-羟色胺、神经肽、细胞因子等。其中，组胺主要存在于肥大细胞内的异染性颗粒中，皮肤血管有H 1、H 2两种受体，而组胺引起的血管扩张及血管通透性增加是两种受体作用的结果。组胺在表皮或基膜中会引起痒感，而被释放到真皮则引起疼痛和水肿。因此，抑制肥大细胞活化脱颗粒进而减少组胺的释放可以缓解皮肤瘙痒。
传统中医药治疗的方法存在使用不便、透皮吸收差、治疗机理不明等不足。而激素类产品只能短期使用，长期使用则有明显的副作用和依赖性，因此不能作为日常护理使用。针对上述问题，本发明提供一种能够从根本上抑制致痒介质-组胺释放，进而有效缓解瘙痒症状的皮肤外用组合物，尤其是化妆品组合物。可将该组合物应用于不同的化妆品配方中，具有使用方便、易于吸收、可长期使用的优点，同时具有良好的止痒效果。
发明内容
一方面，本发明涉及桦树汁和甜菜碱的组合在具有止痒功效的皮肤外用组合物中的用途，其中所述皮肤外用组合物不包含作为单独组分添加的水。
另一方面，本发明提供一种具有止痒功效的皮肤外用组合物，其包含(A)桦树汁和(B)甜菜碱的组合，其中所述皮肤外用组合物不包含作为单独组分添加的水。
所述皮肤外用组合物包括但不限于药物组合物和化妆品组合物，尤其是化妆品组合物，更尤其是护肤化妆品组合物。
本发明的皮肤外用组合物能够抑制肥大细胞释放组胺，因此具有良好的缓解和抑制皮肤瘙痒的功效。与含水体系或与单独使用桦树汁、单独使用甜菜碱的含水体系相比，本发明的皮肤外用组合物提供了显著提高的抗组胺的功效，这表明桦树汁和甜菜碱的组合在无水体系中产生了协同和增效作用。
本发明的皮肤外用组合物不包含任何额外添加的水，但不排除所采用的桦树汁中固有的水分以及其它成分中不可避免引入的少量或痕量的水。
在一个实施方案中，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。
本发明中所涉及的桦树属于桦木科桦树属，可来自白桦(Betula alba)、垂枝桦(Betula Pendula)和亚洲白桦(Betula platyphylla)这三个品种。
所述组分(A)桦树汁，也称桦树液、白桦汁等。桦树汁含有丰富的营养物质，包括糖类、脂肪酸、氨基酸、矿物元素等，其采集时间从积雪开始融化时开始，到树木放叶时为止，采集时在离地40－60公分高的桦树干上钻小孔，置入导液设备，采集桦树汁过滤后，采用常规方法灭菌，得到无杂物、无沉淀、无色透明且营养丰富的汁液。所述桦树汁可购自大兴安岭超越野生浆果开发有限责任公司。
在本发明中，所述桦树汁可以是桦树汁原液形式，也可以是桦树汁浓缩液形式,称为浓缩桦树汁。
本发明人发现，与非浓缩的桦树汁原液和甜菜碱的组合相比，浓缩倍数为1.05-8倍、优选1.1-4倍、更优选1.2-2倍的浓缩桦树汁与甜菜碱的组合显示了更好的缓解皮肤瘙痒的功效。
所述浓缩桦树汁的浓缩方法如下：将新鲜的桦树汁原液输入反渗透循环装置，运行压力控制在0.5-5bar，运行温度控制在20-35℃，然后降温至-65℃，抽真空至0.1Pa，循环，直至桦树汁分别浓缩至1.1倍、1.2倍、1.5倍、2倍、4倍、8倍等。
本发明的皮肤外用组合物可包含5-99.9％重量，优选20-95％重量，更优选35-90％重量的桦树汁，基于所述皮肤外用组合物的总重量。
所述组分(B)甜菜碱，亦称为三甲基甘氨酸，该成分容易与水相互作用，具有优异的保湿性能。本发明中所采用的甜菜碱可获自科耐欧贸易(上海)有限公司等供应商。
本发明的皮肤外用组合物可包含0.01-20％重量，优选0.1-15％重量，更优选1-10％重 量的甜菜碱，基于所述皮肤外用组合物的总重量。
除了上述组分(A)和组分(B)外，本发明的皮肤外用组合物还可以任选地包含(C)药物组合物或者化妆品组合物中常用的成分，其中包括媒介物、表面活性剂、护肤活性成分、药物活性成分和辅料等本领域已知的任何成分，且可根据具体需要选择其类型和用量。通常，组分(C)的含量为0-65％重量，基于所述皮肤外用组合物的总重量计。
所述媒介物是本领域已知的，包括但不限于稀释剂、分散剂或载体等，其实例包括但不限于乙醇、丁二醇、双丙甘醇等。本领域技术人员可根据需要选择其类型和用量。通常，在本发明的皮肤外用组合物中，所述媒介物占所述组分(C)总重量的0.5-20％。
所述表面活性剂是常用于药物或化妆品的任何类型的表面活性剂，其用于降低界面的表面张力，达到清洁、乳化、稳定体系之目的。所述表面活性剂的实例包括但不限于脂肪酸皂(例如月桂酸钠、棕榈酸钠等)、高级烷基硫酸盐(例如月桂基硫酸钠等)、N-酰基肌氨酸(例如月桂酰基肌氨酸钠等)、高级脂肪酸酰胺磺酸盐(例如月桂基甲基牛磺酸钠等)、烷基苯磺酸盐、高级脂肪酸酯硫酸盐(例如硬化椰子油脂肪酸甘油硫酸钠等)、N-酰基谷氨酸盐、月桂基二甲氨基乙酸甜菜碱、烷基甜菜碱、酰氨基甜菜碱、脱水山梨糖醇脂肪酸酯类(例如，脱水山梨糖醇单油酸酯、脱水山梨糖醇单异硬脂酸酯、脱水山梨糖醇单月桂酸酯、脱水山梨糖醇单棕榈酸酯、脱水山梨糖醇单硬脂酸酯、脱水山梨糖醇倍半油酸酯)、甘油聚甘油脂肪酸酯类(例如，单芥酸甘油酯、倍半油酸甘油酯、单硬脂酸甘油酯、单硬脂酸甘油苹果酸酯等)、PEG-脂肪酸酯类(例如，PEG-二硬脂酸酯、二硬脂酸乙二醇酯等)、PEG-烷基醚类(例如PEG-2-辛基十二烷基醚等)、蔗糖脂肪酸酯等中的一种或多种。本领域技术人员可以根据所需选择其类型及用量。通常，在本发明的皮肤外用组合物中，所述表面活性剂占所述组分(C)总重量的0.01-50％。
所述护肤活性成分是本领域已知的，其包括但不限于保湿剂、皮肤调理剂、润肤剂等。
所述保湿剂的实例包括但不限于甘油、海藻糖、蔗糖、泛醇、丙二醇、1,2-戊二醇、甘露醇、甘油聚醚-26、鼠李糖、棉子糖、赤藓醇、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、聚谷氨酸钠、木糖醇、尿素、水解小核菌胶、聚谷氨酸钠、甘油葡糖苷、PPG-10甲基葡糖醚、出芽短梗酶多糖、银耳多糖、PPG-20甲基葡糖醚等中的一种或多种。通常，在本发明的皮肤外用组合物中，所述保湿剂占所述组分(C)总重量的1-30％。
所述润肤剂的实例包括但不限于甘油三(乙基己酸)酯、辛酸/癸酸甘油三酯、葡萄籽油、白池花籽油、牛油果树果脂、鲸蜡醇、聚二甲基硅氧烷、季戊四醇四(乙基己酸)酯、 橄榄油、鳄梨油、玉米油、碳酸二辛酯、胡莫柳酯、角鲨烷、硬脂醇、肉豆蔻酸异丙酯、肉豆蔻醇、氢化聚癸烯、毛瑞榈果油、向日葵籽油、异十六烷、霍霍巴油、羊毛脂、石蜡、微晶蜡、蜂蜡等中的一种或多种。通常，在本发明的皮肤外用组合物中，所述润肤剂占所述组分(C)总重量的0.01-50％。
所述皮肤调理剂可用于保湿、抗皱、祛斑、祛痘、控油等功效。其实例包括但不限于植物甾醇/辛基十二醇月桂酰谷氨酸酯、姜黄根提取物、神经酰胺2、神经酰胺3、水解透明质酸钠、乙酰植物鞘氨醇、胆甾醇、曲酸、抗坏血酸、抗坏血酸葡糖苷、尿囊素、白桦树皮提取物、氢化卵磷脂、熊果苷、传明酸、烟酰胺、乙酰植物鞘氨醇、白藜芦醇、花榈木树皮提取物、毛喉鞘蕊花根提取物、红没药醇、抗坏血酸四异棕榈酸酯、胡椒籽提取物、泛醌、吡哆素二棕榈酸酯、吡哆素二辛酸酯、视黄醇棕榈酸酯、生育酚乙酸酯、燕麦仁提取物等中的一种或多种。通常，在本发明的皮肤外用组合物中，所述皮肤调理剂占所述组分(C)总重量的0.01-50％。
所述药物活性成分是本领域已知的用于缓解皮肤瘙痒的那些成分。其实例包括但不限于苦参提取物、丹皮酚、芳樟醇、桉油素、冰片、硫磺、蝉蜕、蛇床子提取物、地肤子提取物、拳参提取物、紫苏提取物、炉甘石、无患子皂苷、马齿苋提取物、甘草酸铵等。通常，在本发明的皮肤外用组合物中，所述药物活性成分占所述组分(C)总重量的0.01-80％。
所述辅料包括但不限于乳化剂、增稠剂、防腐剂、香料、pH调节剂等。
所述乳化剂的实例包括但不限于山梨坦橄榄油酸酯、硬脂醇聚醚-21、PEG-60氢化蓖麻油、甘油硬脂酸酯/PEG-100硬脂酸酯、PPG-13-癸基十四醇聚醚-24、鲸蜡硬脂基葡糖苷、聚甘油-10肉豆蔻酸酯、鲸蜡硬脂基葡糖苷、聚甘油-10硬脂酸酯、聚甘油-10二油酸酯等中的一种或多种。通常，在本发明的皮肤外用组合物中，所述乳化剂占所述组分(C)总重量的0.01-10％。
所述增稠剂的实例包括但不限于羟乙基纤维素、羟丙基纤维素、卡波姆、黄原胶、阿拉伯胶、聚乙二醇-14M、聚乙二醇-90M、琥珀酰聚糖、丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物等中的一种或多种。本领域技术人员可根据需要具体选择其类型和用量。
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、山梨酸钾、苯甲酸钠、氯苯甘醚等中的一种或多种及其它防腐增效剂，如戊二醇、己二醇、辛甘醇、对羟基苯乙酮等。通常，在本发明的皮肤外用组合物中，所述防腐剂占所述组分(C)总重量的0.01-10％。
所述pH调节剂的实例包括但不限于柠檬酸、柠檬酸钠、精氨酸、三乙醇胺等中的一种或多种。本领域技术人员可根据具体需要选择其类型和用量。
本发明的皮肤外用组合物制备可以通过本领域已知的任何合适的方法制备。例如，可使用本领域中常用的溶解槽、乳化锅、分散器、输送泵等容器来制备。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，分别将两个釜的温度加热至80℃左右，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，任选加入香精、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。可根据需要制备液体、乳液、膏、霜或凝胶等各种剂型的药物组合物或者化妆品组合物，其中所述化妆品组合物可以是化妆水、喷雾、乳液、精华、BB霜、防晒霜等各种形式。
实施例
以下结合具体的实施例对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以更详细地解释本发明，并不用于限定本发明。所有类似的替换和改动对本领域技术人员来说是显而易见的，他们都被视为包括在本发明的范围内。
实施例1：制备实验组与对照组样品
在本实施例中，分别制备了具有下述配方的组合样品，其中组合A-1、A-2、A-3为本发明，组合B-E为对照。
Figure PCTCN2020073125-appb-000001
上述配方制备工序如下：将桦树汁、浓缩桦树汁或水加热至80℃，随后将甜菜碱加入，搅拌均匀后待用。所得样品均为无色透明溶液。
实施例2：实验组和对照组对RBL-2H3细胞释放组胺的影响
根据下述测试方法，测试上述制备的样品A-E对RBL-2H3细胞释放组胺的影响。
实验原理：化合物48/80(N-甲基-对甲氧基苯乙胺和甲醛缩合产生的聚合物)是引起肥大细胞脱颗粒反应的工具药，其机制是作用于肥大细胞膜，引起细胞内钙离子的增加从而使第二信使cAMP和cGMP量发生改变，导致肥大细胞脱颗粒并释放组胺。
实验材料：细胞RBL-2H3细胞株由浙江省医学科学院动物中心提供；测试样品包括上述七种样品组合，试剂包括胎牛血清、台式盐、化合物48/80、组胺Elisa试剂盒。
测试步骤：
Figure PCTCN2020073125-appb-000002
实验结果：实验结果总结于下表1。
表1：细胞模型组胺释放量测试结果
  释放量％ P值(vs模型) P值(vs组合A-1)
模型组 72.7±3.2 - 0.000
组合A-1 30.9±1.1 0.000 -
组合A-2 36.3±1.6 0.000 0.003
组合A-3 40.4±1.0 0.000 0.009
组合B 45.1±2.9 0.000 0.004
组合C 51.8±3.9 0.001 0.001
组合D 57.5±4.7 0.004 0.001
组合E 59.9±2.8 0.003 0.000
上述细胞实验结果表明，与对照组合B-E相比，在本发明范围内的组合A-1、A-2和A-3均更加显著地降低了组胺的释放量。这表明，桦树汁和甜菜碱的组合或者浓缩桦树汁和甜菜碱的组合均对组胺释放的抑制具有协同或者增效作用，且1.3倍的浓缩桦树汁和甜 菜碱的组合显示了进一步更好的效果。
实施例3实验组和对照组对肥大细胞释放白介素-4(IL-4)的影响
根据下述测试方法，测试上述制备的7组样品A-E对肥大细胞释放IL-4的影响。
实验原理:特异性抗原与联结在细胞膜上的IgE抗体交联，导致细胞激活，快速分泌与颗粒有关的炎性介质(组胺、IL-4和IL-13等)。除免疫触发外，肥大细胞的脱颗粒反应可由抗IgE、化合物48/80等非特异性触发剂引起，这些试剂表现出多与依赖IgE释放介质类似的特征。本研究应用化合物48/80刺激肥大细胞脱颗粒释放炎性介质IL-4，考察受试样品对肥大细胞过敏反应的保护功效。
实验材料：肥大细胞由浙江省医学科学院动物中心提供。试剂包括胎牛血清、RPM1640培养基、台式盐、化合物48/80、色甘酸钠、Elisa(白介素-4)试剂盒。受试样品包括对照组、模型组、阳性药物(色甘酸钠)组和上述7组样品A-E。
实验方法：以RPMI1640培养基配制各样品，每组样品设8个复孔。以5*10 6/mL的密度接种肥大细胞到96孔培养板中，每孔90μL，加入10μL/孔的对应样品；置于5％的CO 2培养箱中在37℃进行培养，4h后取出；然后，除对照组外，其余各组加入刺激物48/80(终浓度20mg/L)，继续在培养箱中于37℃孵育2小时，然后在1500rpm下离心5分钟，取上清液，用白介素-4Elisa试剂盒检测上清液中IL-4的含量。
实验结果：实验结果总结于下表2。
表2：细胞模型IL-4释放量测试结果
  释放量％ P值(vs模型)
对照组 34.4±7.9 0.000
模型组 67.6±9.9 -
阳性药物组 44.2±12.3 0.003
组合A-1 50.8±14.7 0.014
组合A-2 52.9±15.7 0.035
组合A-3 53.2±11.3 0.031
组合B 55.7±12.5 0.043
组合C 57.6±15.0 0.083
组合D 61.4±12.1 0.109
组合E 61.6±9.1 0.132
结果表明，与对照组合B-E相比，在本发明范围内的组合A-1、A-2和A-3均更加显著地抑制(p<0.05)化合物48/80刺激肥大细胞导致的IL-4的释放。这表明，桦树汁和甜菜碱的组合或者浓缩桦树汁和甜菜碱的组合均对IL-4释放的抑制具有协同或者增效作用，且1.3倍的浓缩桦树汁和甜菜碱的组合显示了进一步更好的效果。
实施例4：具有止痒功效的喷雾组合物的制备
该实施例提供了一种具有止痒功效的喷雾组合物，其配方如下：
Figure PCTCN2020073125-appb-000003
上述喷雾组合物如下制备：
1.将桦树汁加热至80℃，依次加入甜菜碱、柠檬酸、甘油、羟苯甲酯、丁二醇和戊二醇混合，搅拌溶解均匀；
2.将植物甾醇/辛基十二醇月桂酰谷氨酸酯、甘油三(乙基己酸)酯、甘油聚醚-26和PEG-60氢化蓖麻油加热至80℃，搅拌均匀后加入1所得混合物；
3.降温至40℃，加入苯氧乙醇后，精氨酸调pH，出料。
使用效果测试：选取30位40岁以上老年皮肤瘙痒症患者，男女不限，发病时仅有瘙痒而无原发皮损。每日早晚身体清洁后，将上述喷雾组合物应用于瘙痒部位。组合物使用前及使用4周后，分别针对瘙痒情况进行自评，按照改善程度不同分为明显改善、较明显改善、有一定改善、无明显改善、完全没有改善。结果发现，27位患者(90％)的瘙痒程度在使用产品后发生明显改善，而另外3位患者也有不同程度的改善。表明该喷雾组合物具有优异的止痒效果。
实施例5：具有止痒功效的乳液组合物的制备
该实施例提供了一种具有止痒功效的乳液组合物，其配方如下：
Figure PCTCN2020073125-appb-000004
Figure PCTCN2020073125-appb-000005
上述乳液组合物如下制备：
1.水相：桦树汁、甘油、甜菜碱、泛醇、尿囊素、水解透明质酸钠、戊二醇、黄原胶、卡波姆、羟苯甲酯混合后加热至80℃，搅拌溶解均匀；
2.油相：鲸蜡醇、甘油硬脂酸酯/PEG-100硬脂酸酯、辛酸/癸酸甘油三酯、甘油三(乙基己酸)酯、牛油果树果脂。将上述原料加热至80℃，搅拌溶解均匀；
3.将水相和油相混合后均质乳化5分钟，乳化完成后，加入精氨酸，搅拌15分钟后，降温冷却至40℃，加入苯氧乙醇。
使用效果测试：选取30位40岁以上老年皮肤瘙痒症患者，男女不限，发病时仅有瘙痒而无原发皮损。每日早晚身体清洁后，将上述乳液组合物应用于瘙痒部位。组合物使用前及使用4周后，分别针对瘙痒情况进行自评，按照改善程度不同分为明显改善、较明显改善、有一定改善、无明显改善、完全没有改善。结果发现，28位患者(93.3％)的瘙痒程度在使用产品后发生明显改善，而另外2位患者也有不同程度的改善。表明该乳液组合物具有优异的止痒效果。
实施例6：具有止痒功效的身体乳组合物的制备
该实施例提供了一种具有止痒功效的身体乳组合物，其配方如下：
Figure PCTCN2020073125-appb-000006
Figure PCTCN2020073125-appb-000007
上述身体乳组合物如下制备：
1.水相：桦树汁、甘油、甜菜碱、泛醇、尿囊素、水解透明质酸钠、双丙甘醇、海藻糖、氢化卵磷脂、黄原胶、卡波姆、丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物、羟苯甲酯混合后加热至80℃，搅拌溶解均匀；
2.油相：甘油硬脂酸酯/PEG-100硬脂酸酯、辛酸/癸酸甘油三酯、聚甲基硅倍半氧烷、肉豆蔻醇、蜂蜡、硬脂醇、硬脂酸、牛油果树果脂、聚二甲基硅氧烷。将上述原料加热至80℃，搅拌溶解均匀；
3.将水相和油相混合后均质乳化5分钟，乳化完成后，加入三乙醇胺，搅拌15分钟后，降温冷却至40℃，加入苯氧乙醇、燕麦仁提取物、辛甘醇、烟酰胺。
使用效果测试：选取30位40岁以上老年皮肤瘙痒症患者，男女不限，发病时仅有瘙痒而无原发皮损。每日早晚身体清洁后，将上述身体乳组合物应用于瘙痒部位。组合物使用前及使用4周后，分别针对瘙痒情况进行自评，按照改善程度不同分为明显改善、较明显改善、有一定改善、无明显改善、完全没有改善。结果发现，29位患者(96.7％)的瘙痒程度在使用产品后发生明显改善，而另外1位患者也有较明显的改善。表明该身体乳组合物具有优异的止痒效果。
实施例7：具有止痒功效的膏霜组合物的制备
该实施例提供了一种具有止痒功效的膏霜组合物，其配方如下：
Figure PCTCN2020073125-appb-000008
上述膏霜组合物如下制备：
1.水相：桦树汁、甜菜碱、甘油、泛醇、尿囊素、水解透明质酸钠、甘油聚醚-26、黄原胶、卡波姆、羟苯甲酯；
2.油相：鲸蜡醇、甘油辛酸酯/癸酸酯、季戊四醇四(乙基己酸)酯、甘油硬脂酸酯/PEG-100硬脂酸酯、牛油果树果脂、聚二甲基硅氧烷、羟苯丙酯。将上述原料加热至80℃，搅拌溶解均匀；
3.将水相和油相混合后均质乳化5分钟，乳化完成后，加入精氨酸，搅拌15分钟后，降温冷却至40℃，依次加入苯氧乙醇、辛甘醇。
使用效果测试：选取30位40岁以上老年皮肤瘙痒症患者，男女不限，发病时仅有瘙痒而无原发皮损。每日早晚身体清洁后，将上述膏霜组合物应用于瘙痒部位。组合物使用前及使用4周后，分别针对瘙痒情况进行自评，按照改善程度不同分为明显改善、较明显改善、有一定改善、无明显改善、完全没有改善。结果发现，28位患者(93.3％)的瘙痒程度在使用产品后发生明显改善，而另外2位患者也有较明显的改善。表明该膏霜组合物具有优异的止痒效果。
以上所述实施例的技术方案是本发明优选实施方式，并不构成对所附权利要求书的范围的限制。在不脱离本发明精神和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 (10)

  1. 桦树汁和甜菜碱的组合在具有止痒功效的皮肤外用组合物中的用途，其中所述皮肤外用组合物不包含作为单独组分添加的水。
  2. 根据权利要求1所述的用途，其中所述桦树汁是桦树汁原液。
  3. 根据权利要求1所述的用途，其中所述桦树汁是浓缩倍数为1.05-8倍、优选1.1-4倍、更优选1.2-2倍的浓缩桦树汁。
  4. 根据权利要求1-3任一项所述的用途，其中所述皮肤外用组合物为药物组合物或化妆品组合物。
  5. 一种具有止痒功效的皮肤外用组合物，其包含(A)桦树汁与(B)甜菜碱的组合，其中所述皮肤外用组合物不包含作为单独组分添加的水。
  6. 根据权利要求5所述的组合物，其中所述桦树汁是桦树汁原液。
  7. 根据权利要求5所述的组合物，其中所述桦树汁是浓缩倍数为1.05-8倍、优选1.1-4倍、更优选1.2-2倍的浓缩桦树汁。
  8. 根据权利要求5-7任一项所述的组合物，其为药物组合物或化妆品组合物。
  9. 根据权利要求5-8任一项所述的组合物，其包含5-99.9％重量，优选20-95％重量，更优选35-90％重量的桦树汁，基于所述皮肤外用组合物的总重量。
  10. 根据权利要求5-9任一项所述的组合物，其包含0.01-20％重量，优选0.1-15％重量，更优选1-10％重量的甜菜碱，基于所述皮肤外用组合物的总重量。
PCT/CN2020/073125 2019-07-30 2020-01-20 具有止痒功效的皮肤外用组合物 WO2021017448A1 (zh)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP20848631.6A EP4005553A4 (en) 2019-07-30 2020-01-20 EXTERNAL COMPOSITION FOR THE SKIN INTENDED TO RELIEVE ITCHING
KR1020227002439A KR20220025833A (ko) 2019-07-30 2020-01-20 가려움증 완화 효과를 가진 피부 외용제 조성물
US17/619,488 US20220370534A1 (en) 2019-07-30 2020-01-20 External composition for skin having itching relieving effect

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201910694724.3 2019-07-30
CN201910694724.3A CN110227088B (zh) 2019-07-30 2019-07-30 具有止痒功效的皮肤外用组合物

Publications (1)

Publication Number Publication Date
WO2021017448A1 true WO2021017448A1 (zh) 2021-02-04

Family

ID=67856051

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/073125 WO2021017448A1 (zh) 2019-07-30 2020-01-20 具有止痒功效的皮肤外用组合物

Country Status (6)

Country Link
US (1) US20220370534A1 (zh)
EP (1) EP4005553A4 (zh)
JP (1) JP7437951B2 (zh)
KR (1) KR20220025833A (zh)
CN (1) CN110227088B (zh)
WO (1) WO2021017448A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110227088B (zh) * 2019-07-30 2021-11-19 养生堂（安吉）化妆品有限公司 具有止痒功效的皮肤外用组合物
CN113648372A (zh) * 2021-09-10 2021-11-16 张掖市中医医院 一种治疗皮肤病的外用软膏剂药物及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103565705A (zh) * 2013-11-26 2014-02-12 谢伯平 一种洗发香波
CN107019660A (zh) * 2017-04-27 2017-08-08 养生堂（上海）化妆品研发有限公司 保湿化妆品组合物
CN107049865A (zh) * 2017-04-27 2017-08-18 养生堂（上海）化妆品研发有限公司 护肤化妆品组合物
CN108670878A (zh) * 2018-08-01 2018-10-19 养生堂（安吉）化妆品有限公司 抗皮肤过敏的化妆品组合物
CN110227088A (zh) * 2019-07-30 2019-09-13 养生堂（安吉）化妆品有限公司 具有止痒功效的皮肤外用组合物
CN110731923A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 增强的保湿化妆品组合物

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006131546A (ja) 2004-11-05 2006-05-25 Asahi Kasei Life & Living Corp 白樺樹液含有入浴剤
JP2008074796A (ja) 2006-09-22 2008-04-03 Just World Inc 抗糖尿病食品
CN105878119B (zh) * 2016-05-26 2018-10-09 钦州学院 一种桦树液化妆水及其制备方法
CN107184411B (zh) 2017-04-21 2019-02-22 韩后化妆品股份有限公司 一种复合水嫩因子、化妆品及化妆品的制备方法
CN110731928A (zh) 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 抗衰老化妆品组合物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103565705A (zh) * 2013-11-26 2014-02-12 谢伯平 一种洗发香波
CN107019660A (zh) * 2017-04-27 2017-08-08 养生堂（上海）化妆品研发有限公司 保湿化妆品组合物
CN107049865A (zh) * 2017-04-27 2017-08-18 养生堂（上海）化妆品研发有限公司 护肤化妆品组合物
CN108670878A (zh) * 2018-08-01 2018-10-19 养生堂（安吉）化妆品有限公司 抗皮肤过敏的化妆品组合物
CN110227088A (zh) * 2019-07-30 2019-09-13 养生堂（安吉）化妆品有限公司 具有止痒功效的皮肤外用组合物
CN110731923A (zh) * 2019-07-30 2020-01-31 浙江养生堂天然药物研究所有限公司 增强的保湿化妆品组合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4005553A4 *

Also Published As

Publication number Publication date
CN110227088B (zh) 2021-11-19
JP7437951B2 (ja) 2024-02-26
CN110227088A (zh) 2019-09-13
EP4005553A4 (en) 2023-01-25
JP2021020884A (ja) 2021-02-18
EP4005553A1 (en) 2022-06-01
KR20220025833A (ko) 2022-03-03
US20220370534A1 (en) 2022-11-24

Similar Documents

Publication Publication Date Title
WO2018196481A1 (zh) 保湿化妆品组合物
WO2018196482A1 (zh) 护肤化妆品组合物
JP6891211B2 (ja) 抗アレルギー化粧品組成物
CN110731923B (zh) 增强的保湿化妆品组合物
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
EA006440B1 (ru) Средство для местного лечения, ухода и предупреждения возникновения повреждений кожной ткани, способ его получения и применение
WO2002007745A1 (fr) Compositions antipruritiques et compositions favorisant la suberification des blessures
CN113197836A (zh) 一种保湿舒缓止痒护肤乳霜及其制备方法
WO2021017912A1 (zh) 保湿化妆品组合物
KR20220044974A (ko) 항-습진 효과가 향상된 피부 외용 조성물
WO2021017834A1 (zh) 具有抗炎功效的皮肤外用组合物
WO2021017448A1 (zh) 具有止痒功效的皮肤外用组合物
CN117045523A (zh) 一种高含量壬二酸组合物及其制备方法
KR20190103255A (ko) 주사의 치료를 위한 퐁가미아 오일 및 4-t-부틸시클로헥사놀의 조합물을 포함하는 화장 조성물
CN108056931A (zh) 一种祛痘霜及其制备方法
KR100892742B1 (ko) 여드름 치료용 피부 외용제 조성물
KR20160020038A (ko) 프랜지패니 오일 또는 프랜지패니 오일의 발효물을 포함하는 화장료 조성물
CN114712260B (zh) 具有舒缓修护美白功效的皮肤外用组合物
WO2019209224A2 (en) Topical compositions for the treatment of dermatitis
KR102575645B1 (ko) 여드름 원인균 프로피오니박테리움 아크네스에 대한 항균성 무자극 피부 외용제 조성물
KR102082580B1 (ko) 죽여 추출물의 안정화 방법 및 안정화된 죽여 추출물을 함유하는 화장료 조성물
KR20170130159A (ko) 수용성 프로폴리스를 함유하는 여드름의 예방 또는 치료용 조성물
JPH08165244A (ja) 皮膚疾患治療剤
JP2807792B2 (ja) 皮膚外用剤
CN117815095A (zh) 一种具有舒缓修护作用的组合物及其制备方法

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: 20848631

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 20227002439

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2020848631

Country of ref document: EP

Effective date: 20220228