WO2017057418A1 - Liposome - Google Patents

Liposome Download PDF

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Publication number
WO2017057418A1
WO2017057418A1 PCT/JP2016/078545 JP2016078545W WO2017057418A1 WO 2017057418 A1 WO2017057418 A1 WO 2017057418A1 JP 2016078545 W JP2016078545 W JP 2016078545W WO 2017057418 A1 WO2017057418 A1 WO 2017057418A1
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Prior art keywords
liposome
lecithin
acid
triglyceride
present
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PCT/JP2016/078545
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English (en)
Japanese (ja)
Inventor
行雄 中村
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小林製薬株式会社
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Publication of WO2017057418A1 publication Critical patent/WO2017057418A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K47/24—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
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • 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
    • A61K8/55—Phosphorus compounds
    • 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
    • A61K8/63—Steroids; Derivatives thereof
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • 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
    • A61K9/127—Liposomes
    • 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 a liposome that can be easily formed and has excellent stability.
  • the present invention also relates to an external composition using the liposome.
  • Liposomes are nano-sized vesicles composed of phospholipid bilayer membranes, which are the main components of biological membranes, and have a skin permeation function. Therefore, as a carrier enclosing components having cosmetic activity and pharmacological activity, It is used in various external compositions.
  • Patent Document 2 discloses an average particle size using hydrogenated soybean phospholipid having a phosphatidylcholine content of 90% by mass or more, cholesterol, an N-acyl amino acid salt, and a copolymer of methacryloyloxyethyl phosphorylcholine and butyl methacrylate. It has been reported that liposomes for cosmetics adjusted to 50 to 500 nm have no sticky feeling, have a smooth feel, and are excellent in stability, moisture retention and compounding of other components.
  • liposomes require the production of high energy by processes such as homogeneous high-pressure treatment, ultrasonic treatment, high-speed stirring, and high-speed cutting liquid treatment in a state where the aqueous phase and the oil phase are mixed.
  • processes such as homogeneous high-pressure treatment, ultrasonic treatment, high-speed stirring, and high-speed cutting liquid treatment in a state where the aqueous phase and the oil phase are mixed.
  • drawbacks such as high cost and difficulty in expanding the production scale.
  • liposomes have the drawback of poor stability, and in order to put into practical use an external composition containing liposomes, a formulation design that improves the stability of the liposomes is required.
  • liposomes having excellent stability can be formed by a simple method without going through steps such as homogeneous high-pressure treatment, it is expected to contribute to dramatic progress in liposome formulation technology.
  • An object of the present invention is to provide a liposome that can be easily formed and has excellent stability. Another object of the present invention is to provide an external composition using the liposome.
  • the present inventor has intensively studied to solve the above problems, and as a result, liposomes containing lecithin, cholesterol and triglyceride in a weight ratio of 1: 0.05 to 0.3: 0.1 to 0.8, respectively, It has been found that even if steps such as homogeneous high-pressure treatment are not performed, it can be formed only by stirring required for general mixing, and has excellent stability. Furthermore, it has also been found that the use of a liposome having an unsaturated fatty acid chain as the triglyceride in the composition described above improves skin familiarity after application to the skin and can give a good gloss to the skin. The present invention has been completed by further studies based on these findings.
  • Item 1 A liposome comprising lecithin, cholesterol, and triglyceride, wherein the weight ratio of lecithin: cholesterol: triglyceride is 1: 0.05 to 0.3: 0.1 to 0.8.
  • Item 2. Item 2. The liposome according to item 1, comprising an unsaturated fatty acid as a constituent fatty acid of the triglyceride.
  • Item 3. Item 3. The liposome according to Item 2, wherein the unsaturated fatty acid has 16 to 18 carbon atoms.
  • Item 4. Item 4. The liposome according to Item 2 or 3, wherein the proportion of unsaturated fatty acid in the total fatty acid of triglyceride is 50 to 100%.
  • Item 5. The liposome according to any one of Items 1 to 4, further comprising at least one selected from the group consisting of hyaluronic acid, a hydrolyzate thereof, and a salt thereof.
  • Item 6. A composition for external use containing the liposome according to any one of Items 1 to 5.
  • Item 7. The composition for external use according to Item 6, which is a cosmetic.
  • Item 8. A method for producing liposomes, comprising a step of adding a mixture containing lecithin, cholesterol, and triglyceride in a weight ratio of 1: 0.05 to 0.3: 0.1 to 0.8 to an aqueous solution and stirring the mixture. .
  • the liposome of the present invention can be formed only by stirring required for general mixing without performing steps such as homogeneous high-pressure treatment, production efficiency can be improved and production cost can be reduced.
  • the liposome of the present invention is excellent in stability and can stably maintain the liposome form even when stored for a long period of time.
  • the liposome of the present invention when triglyceride containing an unsaturated fatty acid chain is used as a constituent fatty acid, skin familiarity is improved, it is possible to give a good gloss to the skin, and a good feeling of use may be obtained. it can.
  • the liposome of the present invention contains lecithin, cholesterol, and triglyceride, and the weight ratio of lecithin: cholesterol: triglyceride is 1: 0.05 to 0.3: 0.1 to 0.8.
  • the liposome of the present invention will be described in detail.
  • Lecithin The liposome of the present invention contains lecithin.
  • lecithin is considered to function as a membrane constituent of the liposome.
  • lecithin used in the present invention include natural lecithin obtained from animals or plants and containing unsaturated fatty acid chains as fatty acid chains.
  • Lecithin contains many unsaturated double bonds, and the iodine value is usually 20 or more.
  • the iodine value of lecithin is preferably 25 or more, more preferably 30 or more.
  • the upper limit of the iodine value of lecithin is usually 120 or less, preferably 100 or less, and more preferably 95 or less.
  • the type of phospholipid contained in lecithin is not particularly limited, and examples thereof include phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, and phosphatidic acid.
  • the lecithin used in the present invention may be composed of one of these phospholipids alone, or may be composed of a combination of two or more.
  • the lecithin used in the present invention has a phosphatidylcholine content of 10% by weight or more, preferably 15% by weight or more, more preferably 20% from the viewpoint of further improving the ease of liposome formation, stability, and skin familiarity.
  • the lecithin which is weight% or more is mentioned.
  • the upper limit of the phosphatidylcholine content is not particularly limited, but may be 95% by weight or less.
  • the origin of lecithin used in the present invention is not particularly limited and may be derived from animals or plants.
  • animal-derived lecithin examples include egg yolk lecithin and seafood-derived lecithin. These animal-derived lecithins may be used alone or in combination of two or more.
  • plant-derived lecithin specifically, soybean lecithin, sesame lecithin, corn lecithin, flax lecithin, olive lecithin, rice lecithin, rape lecithin, sunflower lecithin, safflower lecithin, cottonseed lecithin, cotton lecithin, Examples include gray precitin, avocado lecithin, palm lecithin, palm lecithin and the like. These plant-derived lecithins may be used alone or in combination of two or more.
  • lecithin may be used alone or in combination of two or more.
  • the lecithin used in the present invention is preferably egg yolk lecithin, soybean lecithin, and more preferably egg yolk lecithin from the viewpoint of further improving the ease of formation of liposomes, stability, and skin familiarity.
  • the lecithin used in the present invention may be a purified product, but may contain other components as long as lecithin is contained.
  • the yolk lower alcohol extract is obtained by extracting egg yolk from lipids such as lecithin and other oils and fats with lower alcohols such as ethanol and isopropanol, in addition to egg yolk lecithin, there are many cholesterol and triglycerides. It is included and exceeds the upper limit (1: 0.3: 0.8) of the lecithin: cholesterol: triglyceride weight ratio characteristic of the liposomes of the present invention.
  • the yolk lower alcohol extract preferably contains 15% by weight or more of egg yolk lecithin, preferably 20% by weight or more, and more preferably 25% by weight or more.
  • Lecithin is commercially available, and commercially available lecithin can be used in the present invention.
  • Examples of commercially available lecithin include, for example, NOF Corporation (trade name: COATSOME NC-20 (SPC)) and Lipoid (trade name: LIPOID P100) as soy lecithin, and egg yolk lecithin.
  • NOF Corporation trade name: COATSOME NC-50 (EPC)
  • Lipoid trade name: LIPOID E PC S
  • QP Corporation trade name: egg yolk lecithin PL-30S
  • Cholesterol The liposome of the present invention further contains cholesterol.
  • cholesterol becomes a membrane component of the liposome, and is contained at a predetermined ratio, thereby contributing to improvement in the ease of formation and stability of the liposome.
  • cholesterol used in the present invention those obtained from animals or plants may be used, and those produced by microbial culture, chemical synthesis, enzyme reaction, etc. may be used.
  • Cholesterol is commercially available, and in the present invention, commercially available cholesterol can be used.
  • Commercially available cholesterols include, for example, Croda Japan Co., Ltd. (trade name: COLSTEROL NF), Nippon Seika Co., Ltd. (trade name: Cholesterol JSQI, Japanese Pharmacopoeia Cholesterol), Nippon Suisan Co., Ltd. (trade name: Nissui Marine Cholesterol) and the like.
  • the liposome of the present invention further contains triglyceride.
  • triglyceride serves as a membrane constituent of the liposome and is contained at a predetermined ratio, thereby contributing to improvement in the ease of formation and stability of the liposome.
  • the constituent fatty acid of the triglyceride used in the present invention may be either an unsaturated fatty acid or an unsaturated fatty acid.
  • the carbon number of the constituent fatty acids of triglyceride (the number of carbon atoms per fatty acid residue) is not particularly limited, and examples thereof include 12 to 20, preferably 14 to 20. More specifically, from the viewpoint of further improving the ease of formation and stability of liposomes, the constituent fatty acids of triglyceride are unsaturated as the number of carbons of the constituent fatty acids of triglyceride (the number of carbon atoms per fatty acid residue). In the case of a fatty acid, more preferably 16 to 18; when the constituent fatty acid of triglyceride is a saturated fatty acid, 14 to 18 are more preferable.
  • unsaturated fatty acids among the constituent fatty acids of triglycerides include palmitoic acid, palmitoleic acid, oleic acid, vaccenic acid, linoleic acid, ⁇ -linolenic acid, ⁇ -linolenic acid, arachidonic acid and the like.
  • palmitoic acid, palmitoleic acid, oleic acid, vaccenic acid, and linoleic acid are preferred from the viewpoint of further improving the ease of liposome formation, stability, skin familiarity, and gloss imparted to the skin.
  • saturated fatty acid among the constituent fatty acids of triglyceride include lauric acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, arachidic acid and the like.
  • myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, and more preferably stearic acid are preferable from the viewpoint of further improving the ease of liposome formation and stability. .
  • the three constituent fatty acids contained in one molecule of triglyceride may be unsaturated fatty acids or saturated fatty acids, one or two may be unsaturated fatty acids, and two or one may be saturated fatty acids.
  • triglycerides triglycerides containing at least one unsaturated fatty acid as a constituent fatty acid can further improve the ease of formation and stability of liposomes, and impart good gloss to the skin while improving skin familiarity. This is preferable.
  • triglycerides in which at least two are unsaturated fatty acids are more preferred and the three constituent fatty acids Triglycerides in which all of the constituent fatty acids are unsaturated fatty acids are more preferred, triglycerides in which all of the three constituent fatty acids are unsaturated fatty acids having 16 to 18 carbon atoms are particularly preferred, and triglycerides in which all of the three constituent fatty acids are oleic acid (triolein) ) Is most preferred.
  • triglycerides may be used singly or in combination of two or more.
  • the triglyceride contained in the liposome of the present invention has all the constituent fatty acids.
  • the proportion of unsaturated fatty acids is preferably 50 to 100%, more preferably 55 to 100%, more preferably 60 to 100%.
  • the ratio of the unsaturated fatty acid to the total constituent fatty acid of the triglyceride means that the number of constituent fatty acid chains per molecule of the total triglyceride is 3, and the constituent fatty acids of the total triglyceride contained in the liposome of the present invention is It is the ratio of the number of unsaturated fatty acid chains to the total number of chains.
  • Ratio of lecithin, cholesterol and triglyceride in the liposome of the present invention, is set to satisfy 1: 0.05 to 0.3: 0.1 to 0.8. By satisfying such a ratio, it is possible to easily form liposomes and to provide excellent stability.
  • the weight ratio of lecithin: cholesterol: triglyceride is preferably 1: 0.1 to 0.3: 0.1 to 0.8, more preferably 1: 0.1-0.2: 0.1-0.6. Moreover, when using the triglyceride containing an unsaturated fatty acid as a triglyceride while satisfying such a ratio, it becomes possible to improve the skin familiarity and the gloss given to the skin more effectively.
  • the liposome of the present invention may contain other membrane constituent components as necessary, as long as the effects of the present invention are not disturbed, in addition to the components described above.
  • membrane constituents include phospholipid polymers, sterols other than cholesterol, charged substances, acylamino acid surfactants, and the like.
  • Examples of the phospholipid polymer include polymethacryloyloxyethyl phosphorylcholine, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate / sodium methacrylate copolymer, 2-methacryloyl Examples thereof include oxyethyl phosphorylcholine ⁇ 2-hydroxy-3-methacryloyloxypropyltrimethylammonium chloride copolymer, 2-methacryloyloxyethyl phosphorylcholine ⁇ stearyl methacrylate copolymer, and the like.
  • phospholipid polymers a 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer is preferable.
  • These phospholipid polymers may be used individually by 1 type, and may be used in combination of 2 or more type.
  • sterols examples include cholesteryl acetate, cholesteryl nonanoate, cholesteryl stearate, cholesteryl isostearate, cholesteryl oleate, phytosteryl isostearate, phytosteryl stearate, phytosteryl oleate, phytosteryl palmitate, soft lanolin fatty acid cholesteryl, and hard lanolin fatty acid Cholesteryl, long-chain branched fatty acid cholesteryl, long-chain ⁇ -hydroxy fatty acid cholesteryl, N-lauroyl-L-glutamate di (cholesteryl / behenyl / octyldodecyl), N-lauroyl-L-glutamate di (cholesteryl / octyldodecyl), N- Lauroyl-L-glutamate di (phytosteryl 2-octyldodecyl), cholesteryl 12-hydroxystearate And the like. These sterols may be
  • Examples of the charged substance include fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, elaidic acid, eleostearic acid, and 2,4-octadecadienoic acid; their sodium salts, potassium salts, Fatty acid salts such as calcium salts and ammonium salts; phosphatidic acid, dicetyl phosphate and the like. Further, when phosphatidylglycerol or a salt thereof is used as the phospholipid component, it itself acts as a charged substance. These charged substances may be used alone or in combination of two or more.
  • acylamino acid surfactants include fatty acid amide salts of amino acids such as sarcosine, glutamic acid, taurine, glycine and the like. These acylamino acid surfactants may be used alone or in combination of two or more.
  • the liposome of the present invention may contain an active ingredient exhibiting cosmetic activity or pharmacological activity, if necessary.
  • active ingredients include, but are not limited to, water-soluble vitamins and derivatives thereof, oil-soluble vitamins and derivatives thereof, glycyrrhizic acid and derivatives thereof, glycyrrhetinic acid and derivatives thereof, astaxanthin, coenzyme Q10, ⁇ - Lipoic acid, ceramide or similar substances, linoleic acid, arbutin, tranexamic acid, kojic acid, enzymes, peptides, hormones, various cytokines, hyaluronic acid, salts thereof, etc., glycosaminoglycans and salts thereof or derivatives thereof, hyaluron Acid hydrolyzate or salt thereof, collagen or hydrolyzate thereof, elastin or hydrolyzate thereof, physiologically active substances such as sugars, various animal and plant extracts, substances obtained by fermentation with microorganis
  • hyaluronic acid, hydrolysates thereof, and salts thereof are active ingredients that are difficult to satisfy skin familiarity with conventional techniques
  • the liposome of the present invention the skin familiarity of hyaluronic acid, a hydrolyzate thereof and / or a salt thereof can be effectively improved.
  • triglyceride containing unsaturated fatty acid is used as the triglyceride, when it contains hyaluronic acid, a hydrolyzate thereof and / or a salt thereof, the gloss given to the skin can be further improved.
  • the active ingredient is preferably hyaluronic acid, a hydrolyzate thereof, and / or a salt thereof, more preferably a hydrolyzate of hyaluronic acid and / or a salt thereof.
  • the average molecular weight of the hydrolyzate of hyaluronic acid is not particularly limited, and examples thereof include 10,000 or less.
  • the active ingredient may be contained in any one of an inner aqueous phase (liposome inner phase), an outer aqueous phase (liposome outer phase), and a membrane interior (in the liposome membrane).
  • an embodiment in which the active ingredient is contained in at least the inner aqueous phase is preferable.
  • the content of the active ingredient in the liposome of the present invention is appropriately set according to the type of active ingredient to be used.
  • the active ingredient is contained in an amount of 0.01 to 100 parts by weight per 100 parts by weight of the total membrane constituent of the liposome. 35 parts by weight, preferably 0.1 to 25 parts by weight, more preferably 0.5 to 20 parts by weight.
  • the liposome of the present invention contains, in addition to the water that forms the inner aqueous phase and the outer aqueous phase, additives that are blended in the composition for external use of the skin as necessary, as long as the effects of the present invention are not hindered. It may be.
  • additives examples include lower monohydric alcohols such as ethanol and isopropanol; polyhydric alcohols such as glycerin and propylene glycol; oils such as squalane and petrolatum; antioxidants such as dibutylhydroxytoluene and sulfite; Examples include preservatives such as ethanol, octoxyglycerin, and paraben; pigments, pearlizing agents, thickeners, surfactants, stabilizers, chelating agents, coloring agents, fragrances, buffers, pH adjusters, and the like.
  • additives may be contained in any of the inner aqueous phase (liposome inner phase), the outer aqueous phase (liposome outer phase), and the inside of the membrane (in the liposome membrane) in the liposome of the present invention.
  • the method for producing the liposome of the present invention is not particularly limited, examples of a simple production method include the following methods.
  • active ingredients and additives that are added as needed are mixed with a fat-soluble component to prepare a mixed solution.
  • an aqueous solution is prepared by mixing water-soluble components among the active ingredients and additives added as necessary.
  • Liposomes are formed by adding the mixed solution to the obtained aqueous solution and stirring.
  • the stirring performed by adding the oily solution to the aqueous solution is not homogenous high-pressure processing or high-speed stirring, but stirring used for general mixing processing is sufficient.
  • the liposome of the present invention can form a liposome without undergoing steps such as homogeneous high pressure treatment required for the formation of a conventional liposome.
  • the liposomes formed by the above method may be subjected to a known sizing treatment to adjust the particle diameter as necessary.
  • a known sizing treatment for example, the method of allowing the filter of a predetermined
  • the average particle size of the liposome of the present invention is not particularly limited, and examples thereof include about 50 to 500 nm.
  • the liposome of the present invention the liposome obtained by the above method may be used as it is, or it may be used as a powdered liposome after being subjected to a known pulverization treatment.
  • the liposome of the present invention is used as a raw material to be added to a composition for external use in skin such as cosmetics and external medicines.
  • a composition for external use in skin such as cosmetics and external medicines.
  • the external composition to which the liposome of the present invention is added may be in any dosage form such as liquid, solid, cream or gel.
  • the external composition to which the liposome of the present invention is added may be an emulsified form such as a water-in-oil emulsion composition, an oil-in-water emulsion composition, or the like.
  • Examples of the preparation form of the external composition to which the liposome of the present invention is added include cosmetics such as creams, lotions, cosmetic liquids, emulsions, gels, lipsticks and foundations; liquids (lotions, sprays, aerosols, and the like) And other external pharmaceuticals such as foams, ointments, creams, gels, patches, and the like.
  • cosmetics are preferable, and creams, lotions, cosmetic liquids, and milky lotions are more preferable.
  • the content of the liposome of the present invention may be appropriately set according to the preparation form and the like.
  • 0.00005 to 5% by weight in terms of lecithin content 0.00005 to 5% by weight in terms of lecithin content.
  • the range is preferably 0.00005 to 3% by weight, more preferably 0.00005 to 2% by weight.
  • composition for external use to which the liposome of the present invention is added includes an active ingredient exhibiting cosmetic activity or pharmacological activity, an additive for preparing a predetermined formulation, water, etc., depending on the formulation form. May be included. About the kind of such an active ingredient and additive, it is the same as that of what was illustrated as an ingredient which can be contained in the inner water phase of the liposome of the present invention, the outer water phase, or the inside of a membrane.
  • Test example 1 Production of Liposome Composition Lecithin (“COATSOME NC-50 (EPC)” manufactured by NOF Corporation, iodine number 66, phosphatidylcholine content 95% by weight), cholesterol (“Cholesterol JSQI” manufactured by Nippon Seika Co., Ltd.), tristearin ( “Esteride GS” manufactured by National Mimatsu Co., Ltd., triglyceride in which 80% or more of the constituent fatty acids are stearic acid) and / or triolein (“Triolein” manufactured by Wako Pure Chemical Industries, Ltd.), 60% of the constituent fatty acids Liposomes were produced using triglycerides, which are oleic acid.
  • lecithin, cholesterol, tristearin and / or triolein are mixed in a predetermined amount shown in Tables 1 and 2 and heated and dispersed at 85 ° C., 85 ° C. purified water is added, and 500 rpm After stirring for 30 seconds, a liposome composition was obtained by cooling to room temperature.
  • X A Maltese cross image is observed before storage (immediately after preparation), and no Maltese cross image is observed after storage.
  • Test example 2 The skin condition of the liposome composition (Examples 2 to 5, 7, 10 and Comparative Examples 1 to 3) obtained in Test Example 1 and the gloss given to the skin were evaluated by 10 evaluation monitors. Specifically, about 0.8 g of each liposome composition was applied to the face and evaluated for skin familiarity and skin gloss. For each evaluation, “1” indicates that skin familiarity is poor, “10” indicates that skin familiarity is good; “1” indicates that skin glossiness is poor, and “10” indicates that skin glossiness is good. "By conducting a questionnaire by Visual Analogue Scale (hereinafter referred to as VAS). The questionnaire results were averaged, and the relative value of the evaluation results of each liposome composition was calculated with the result when the liposome composition of Comparative Example 1 was used as 100.
  • VAS Visual Analogue Scale
  • Table 3 shows the obtained results. From this result, when liposomes were formed using lecithin, cholesterol and triglyceride in a weight ratio of 1: 0.05 to 0.3: 0.1 to 0.8, respectively, the triglyceride was unsaturated as a constituent fatty acid. When triglyceride containing a fatty acid was used, it was confirmed that the familiarity with the skin and the gloss given to the skin were remarkably improved (Examples 2 to 5 and 7).
  • Test example 3 Production of Liposome Composition
  • Liposome compositions (Examples 12 and 13) having the compositions shown in Table 4 were produced.
  • a specific manufacturing method is as follows. First, lecithin (“COATSOME NC-50 (EPC)” manufactured by NOF Corporation, iodine value 66, phosphatidylcholine content 95% by weight), cholesterol (“cholesterol JSQI” manufactured by Nippon Seika Co., Ltd.) and triolein (Wako Pure Chemical Industries, Ltd.) “Triolein” manufactured by Kogyo Co., Ltd., a triglyceride in which 60% or more of the constituent fatty acids are oleic acid, mixed in a predetermined amount shown in Table 4 and heated and dispersed at 85 ° C., sodium hyaluronate (Kikkoman Biochemifa) "FCH-120” manufactured by Co., Ltd., molecular weight 1 million to 1.4 million) or hydrolyzate of hyalur
  • Table 4 also shows the evaluation results of the liposome compositions of Example 3 and Comparative Example 1 obtained in Test Example 1 for reference. As a result, even when hyaluronic acid or a hydrolyzate thereof is contained, lecithin, cholesterol and triglyceride are used in a weight ratio of 1: 0.05 to 0.3: 0.1 to 0.8, respectively. It was confirmed that liposomes having excellent stability can be easily formed. It was also confirmed that the gloss given to the skin was further improved by containing hyaluronic acid or a hydrolyzate thereof.
  • a liposome composition was prepared in the same manner as in Test Example 3 in accordance with the formulations described in Tables 5 and 6. The obtained liposome composition was excellent in stability. In addition, the liposome composition in which triglyceride containing an unsaturated fatty acid as a constituent fatty acid is blended is excellent in terms of skin familiarity and gloss to the skin.
  • a lotion was prepared according to the formulation described in Table 7. Specifically, the components (A) and (B) shown in Table 7 were stirred and dissolved to obtain mixed solutions (A) and (B). To the resulting mixture (B), the mixture (A) was added and stirred, and then the component (C) was added and further stirred to prepare a lotion. In the obtained lotion, the liposome was excellent in stability. It was also confirmed that the gloss applied to the skin was improved by adding a liposome composition containing hyaluronic acid or a hydrolyzate thereof.
  • Formulation Examples 24-26 A lotion was prepared according to the formulation described in Table 8. Specifically, a skin lotion containing liposomes was prepared by the same method as in Test Example 3. The obtained lotion was excellent in the stability of liposomes, and was also excellent in terms of skin familiarity and gloss to the skin.

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Abstract

[Problème] Le but de la présente invention est de fournir un liposome ayant une excellente stabilité et qui peut être formé facilement. [Solution] L'invention concerne un liposome comprenant de la lécithine, du cholestérol et un triglycéride, selon un rapport pondéral de 1/0,05 à 0,3/ 0,1 à 0,8. Le liposome a une excellente stabilité et peut être formé avec seulement l'agitation requise pour des mélanges communs, sans effecteur une homogénéisation à haute pression ou analogue.
PCT/JP2016/078545 2015-09-28 2016-09-27 Liposome WO2017057418A1 (fr)

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Cited By (2)

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CN110448519A (zh) * 2019-08-27 2019-11-15 西安艾尔菲生物科技有限公司 人成纤维细胞调节培养液柔性脂质体及其制备方法和应用
RU2740553C2 (ru) * 2019-01-30 2021-01-15 Анастасия Андреевна Карбаинова Способ получения липосомальной формы бетулина, обладающей гепатопротекторной активностью

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CN110996911B (zh) * 2017-06-26 2023-01-17 福多兹制药公司 阿瑞匹坦的纳米微脂囊配制品及其方法和应用
CN111132753B (zh) 2017-09-04 2022-05-27 一丸自然美健有限公司 pH敏感性脂质体及其制造方法

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JPS63246320A (ja) * 1987-01-27 1988-10-13 ネクスター・フアーマシユーテイカルズ・インコーポレイテツド 非水溶性の有効成分のためのリン脂質輪送ビヒクル
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2740553C2 (ru) * 2019-01-30 2021-01-15 Анастасия Андреевна Карбаинова Способ получения липосомальной формы бетулина, обладающей гепатопротекторной активностью
CN110448519A (zh) * 2019-08-27 2019-11-15 西安艾尔菲生物科技有限公司 人成纤维细胞调节培养液柔性脂质体及其制备方法和应用
CN110448519B (zh) * 2019-08-27 2022-08-30 西安艾尔菲生物科技有限公司 人成纤维细胞调节培养液柔性脂质体及其制备方法和应用

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