JP2014208626A - Liposome composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liposome composition, more specifically, one which has excellent storage stability due to inclusion of a ceramide in a liposome by non-crystallization and which can sufficiently exert barrier function improvement effect even inside a horny layer of rough skin due to percutaneous absorption of the liposome including the non-crystallized ceramide.SOLUTION: A liposome composition is characterized by containing the following components (A) to (D): (A) a ceramide; (B) a dextrin fatty acid ester satisfying the following conditions (1) to (3): (1) the fatty acid has a substitution degree of 1.4 to 1.8 per glucose unit, (2) the fatty acid has a composition of (a) a straight chain saturated fatty acid having a carbon number of 12 to 22 and (b) a branch saturated fatty acid having a carbon number of 8 to 22, where the content molar ratio of (a) and (b) is 60:40 to 95:5, and (3) the glucose in the dextrin moiety has an average polymerization degree of 3 to 150; (C) phospholipid; and (D) cholesterol or phytosterol.

Description

  The present invention relates to a liposome composition, and more specifically, it can be stably contained in a liposome composition without crystallizing ceramides, and further, storage stability, skin roughening improving effect, and moisture retention The present invention relates to a liposome composition having excellent effects.

  Ceramide exists as a major component of intercellular lipids in the stratum corneum, the outermost layer of the skin, and acts as a barrier function that prevents the skin's moisture from transpiration by binding to the protein envelope lining protein. Yes. The decrease in the barrier function of the skin causes the occurrence of small wrinkles, which can be said to be an early symptom of skin aging due to a decrease in the amount of moisture in the skin, and resistance to external factors such as allergens is lost, resulting in various skin troubles. In addition, the decrease in the barrier function visually appears as so-called rough skin, since the skin surface is dried and whitened and desquamated.

  Paying attention to such useful functions of ceramide, studies on inclusion in ceramide-containing cosmetics and skin external preparations have been made. However, ceramide has high crystallinity, and it may be difficult to stably contain it in cosmetics and skin external preparations. Conventionally, combinations with various components, methods of production, and the like have been made. In addition to ceramide, ceramide-like substances such as plant ceramide, synthetic ceramide, and pseudoceramide (synthetic pseudoceramide) are expected to have the same effect as ceramide. Has been made. For example, Patent Document 1 discloses a technique of an oil-in-water emulsion composition in which ceramides, α-tocopheryl phosphates, and batyl alcohol are combined. Patent Document 2 discloses ceramides and carbon atoms having 10 to 10 carbon atoms. There is a fine emulsion aqueous cosmetic technology in which an oil phase containing 30 fatty acids and an aqueous phase are dispersed at high pressure to have a specific pH region or conductivity.

  The rough skin is in a state in which the barrier function is disturbed due to the lack of ceramide and the like not only in the stratum corneum but also in the stratum corneum. In addition, substances with very high crystallinity such as ceramide are hardly absorbed percutaneously, and when a non-crystallized ceramide-containing preparation is applied, the ceramide remains on the stratum corneum surface. Until now, it was not expected to effectively improve the barrier function. Conventionally, as shown in Non-Patent Document 1 and the like, liposomes are known as useful carriers for carrying substances to excellent body tissues. Therefore, Patent Document 3 includes a technique that enhances the transdermal absorbability into the stratum corneum by making a liposome membrane containing a branched alcohol and a ceramide-containing liposome flexible.

  On the other hand, since dextrin fatty acid esters have the action of gelling a liquid oil agent, Patent Document 4 discloses a technique for improving the viscosity and stability of an oil agent system, and Patent Document 5 discloses a dextrin. There is a technique in which a fatty acid ester improves dispersion of powder and stability over time in a water-in-oil emulsion cosmetic.

JP 2011-016761 A JP 2010-083802 A JP 2011-032230 A JP 2010-083866 A JP 2010-116354 A

  Pharmaceutical Journal 128 (2) 185-186 (2008)

In the technique of Patent Document 1 described above, ceramides may be crystallized depending on the temperature environment to be stored. The technique of Patent Document 2 is a technique for refining an emulsion containing ceramides with a specific high-pressure device. However, when observed microscopically with a polarizing microscope or the like, sufficient crystallization of ceramides is suppressed. In some cases, the effect was not exhibited. The technique of Patent Document 3 is a technique for improving transdermal absorbability by containing a branched alcohol having 20 to 24 carbon atoms and softening the membrane of the liposome, but the inclusion of ceramide has crystallinity. In some cases, the storage stability of liposomes may not be sufficiently exhibited, and liposomes that are vesicles composed of lipid bilayers may not be produced due to the influence of branched alcohols, or may not be non-crystallized. Ceramide may not be effectively transdermally absorbed into the stratum corneum.
That is, as described above, there is a formulation technology containing ceramides, but ceramides have high crystallinity and may not have sufficient stability depending on the storage environment. For example, in a high temperature environment, the stability of the liposome itself may be affected, and in the case where ceramides are encapsulated, it may be likely to precipitate. In an environment where the temperature changes in a short period of time (hereinafter, temperature cycle environment), crystallization of ceramides may proceed. For example, depending on the period of use of the preparation, it may occur due to a long-term temperature change depending on the season or a short-term temperature change in an air-conditioning environment. In this case, the presence of the crystallized ceramides can be confirmed by microscopic observation with a polarizing microscope or the like.
And, if ceramides crystallize in the preparation, it becomes difficult to obtain the effect of adhering to the stratum corneum, occlusion effect and transdermal absorption effect, which may affect the skin improvement effect and moisturizing effect. .

  From the above situation, it was necessary to develop a technique that can more stably contain ceramides in the preparation and a preparation that can more effectively improve rough skin. That is, an object of the present invention is to develop a liposome composition as a carrier that can be stably contained without crystallizing ceramides even at high temperature and in a temperature cycle environment and can percutaneously absorb ceramide into the stratum corneum. .

  In view of this situation, the present inventors can combine ceramides with specific dextrin fatty acid esters in order to stably encapsulate ceramide in the lipid bilayer membrane of liposomes and suppress ceramide crystals. It has been found that it is necessary and exerts a remarkable effect on the stabilization of liposomes. As a result of further intensive studies, it was found that a liposome capable of further improving the crystallization-inhibiting effect of ceramides can be obtained by adding cholesterol or phytosterol as a component for improving the stability of the liposome. I found it. Furthermore, by containing a specific oil together with these ceramides and a specific dextrin fatty acid ester, the stability of the ceramides encapsulated in the liposomes, the improvement effect on the skin, and the moisturizing effect can be dramatically enhanced. The present invention has been completed.

That is, the present invention provides the following components (A) to (D);
(A) Ceramides (B) Dextrin fatty acid ester satisfying the following conditions (1) to (3) (1) The degree of substitution of the fatty acid per glucose unit is 1.4 to 1.8 (2) The fatty acid The composition is (a) a linear saturated fatty acid having 12 to 22 carbon atoms and (b) a branched saturated fatty acid having 8 to 22 carbon atoms, and the molar ratio of (a) and (b) is 60:40 to 95: (3) the average degree of polymerization of glucose in the dextrin moiety is 3 to 150 (C) phospholipid (D) cholesterol or phytosterol

  The present invention also relates to a liposome composition, wherein component (B) is a dextrin esterified product of (a) palmitic acid and (b) 2-ethylhexanoic acid.

  The present invention also relates to a liposome composition characterized in that the component (A) is one or more selected from natural ceramides, sphingophospholipids, glycosphingolipids, and phytosphingoglycolipids.

  The present invention also relates to a liposome composition, wherein the mass ratio of components (A) and (B) is (A) / (B) = 0.48-1.

  The present invention also relates to a liposome composition characterized in that the mass ratio of components (A) and (C) is (A) / (C) 0.04 to 0.27.

  In addition, the present invention provides a component (E) a higher alcohol having a branch having 18 to 24 carbon atoms, an ester of a fatty acid having 8 to 18 carbon atoms and a monohydric alcohol having 2 to 16 carbon atoms, a fatty acid having 8 to 18 carbon atoms. And an oil selected from esters of dihydric alcohols having 2 to 16 carbon atoms.

  The present invention also relates to a liposome composition, which is a cosmetic.

  The present invention also relates to a liposome composition characterized by being an external preparation for skin.

  The liposome composition of the present invention is excellent in storage stability because ceramides can be non-crystallized and encapsulated in the liposome, and the liposome composition exhibits an effect of improving skin roughness and a moisturizing effect. Is particularly excellent.

Hereinafter, the present invention will be described in detail. In the present specification, “to” means a range including numerical values before and after.
The ceramides of the component (A) of the present invention are contained as a component for improving a disturbed barrier function and imparting a rough skin improvement effect and a moisturizing effect, and include ceramide and derivatives thereof, natural extracts Or a composite. The ceramides in the present invention are not limited as long as they can be used for cosmetics and the like, but can be defined as follows. That is, a nonionic system having one or more long-chain straight-chain and / or branched alkyl or alkenyl groups, at least two hydroxyl groups, and one or more amide groups (and / or amino groups) in the molecule A series of ceramides expressed as an amphiphilic substance or a derivative in which a phosphatidylcholine residue or a sugar residue is bonded to a hydroxyl group of the nonionic amphiphile. For example, natural ceramides such as sphingosine, phytosphingosine and their long-chain fatty acid amides ceramide 1, ceramide 2, ceramide 3, ceramide 3B, ceramide 4, ceramide 5, ceramide 6, ceramide 6I, ceramide 6II; sphingosine, phyto Examples of sphingosine phospholipid derivatives such as sphingomyelin and phytosphingomyelin; sphingoglycolipids such as cerebroside and ganglioside that are glycosides and phytosphingoglycolipids, etc. They can be used in combination. In the present invention, the ceramides include synthetic ceramides, pseudoceramides and the like, but from the technical advantages of the present invention, among them, natural ceramides are preferable, and particularly excellent rough skin improvement effect and moisturizing effect. In order to be obtained, ceramide 2 or ceramide 3 is preferred.

  The content of the component (A) in the liposome composition of the present invention is preferably 0.001 to 2% by mass (hereinafter abbreviated as “%”), more preferably 0.01 to 1%. Within this range, crystallization of ceramides can be suppressed and ceramides can be stably contained, and a liposome composition excellent in storage stability, rough skin improvement effect and moisturizing effect can be obtained.

Component (B) of the present invention is a dextrin fatty acid ester that satisfies the following conditions (1) to (3): (1) The degree of substitution of the fatty acid per glucose unit is 1.4 to 1.8. (2) The fatty acid composition is a linear saturated fatty acid (a) having 12 to 22 carbon atoms and a branched saturated fatty acid (b) having 8 to 22 carbon atoms, and the molar ratio of (a) and (b) is 60:40 to 95. (3) The average degree of polymerization of glucose in the dextrin portion is 3 to 150.
Hereinafter, the configuration of the component (B) will be further described.

[Degree of fatty acid substitution per glucose unit of dextrin fatty acid ester]
The degree of substitution means an average value of the number of glucose hydroxyl groups substituted with fatty acids, which is a constituent unit of dextrin. In the present invention, it is 1.4 to 1.8, preferably 1.45 per glucose unit. 1.75. As the degree of substitution becomes lower than 1.4, the dissolution temperature becomes higher, and it becomes difficult to produce liposomes, or the esterification itself crystallizes in the liposome composition due to the decrease in solubility, or coloring in the liposome composition Or a peculiar smell is generated, which is not preferable. Further, stickiness occurs as the degree of substitution is greater than 1.8, and smoothness and moisturizing effect in the liposome composition are difficult to obtain.

[Fatty acid part of dextrin fatty acid ester]
The dextrin fatty acid ester of the present invention is characterized in that there are two types of fatty acids to be esterified with dextrin. The fatty acid is (a) a fatty acid having 12 to 22 carbon atoms and (b) a branched saturated fatty acid having 8 to 22 carbon atoms, preferably each a linear saturated fatty acid having 14 to 22 carbon atoms and 8 to 8 carbon atoms. 20 branched saturated fatty acids. One or two or more of these fatty acids may be used.
In the present invention, the fatty acid part of component (B) is characterized by containing (a) and (b), and only in this combination suppresses ceramide crystals and improves the solubility of ceramides. It is something that can be done. That is, when the fatty acid part is an esterified product of either one of (a) or (b) and dextrin, the effect of suppressing the crystals of the ceramides of the present invention is not significantly observed.
When the fatty acid is an ester of a fatty acid and a dextrin mixed with a linear fatty acid having 11 or less carbon atoms and a branched fatty acid having 7 or less carbon atoms, the fatty acid having 23 or more carbon atoms and 21 carbon atoms In any of the cases where the mixed fatty acid and the dextrin are mixed with the above-mentioned branched saturated fatty acid, the effect of suppressing the ceramide crystals of the present invention cannot be obtained. Further, when the fatty acid has a large number of carbon atoms, stickiness as a liposome composition may occur.

  Specific examples of (a) a linear saturated fatty acid having 12 to 22 carbon atoms used in the present invention include lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid and the like. One type or two or more types can be appropriately selected or combined for use. Of these, palmitic acid is particularly preferable. Examples of the (b) branched saturated fatty acid having 8 to 22 carbon atoms used in the present invention include 2-ethylhexanoic acid, isononanoic acid, isodecanoic acid, isotridecanoic acid, isomyristic acid, isopalmitic acid, isostearic acid, Examples include isoarachidic acid, and one or more of these can be appropriately selected or used in combination. Of these, 2-ethylhexanoic acid is particularly preferred.

  In the present invention, it is necessary that these fatty acids are contained in a specific ratio. Specifically, the composition of the fatty acid portion of the total dextrin fatty acid ester in the composition is (a) 60 to 95 mol% of a linear saturated fatty acid having 12 to 22 carbon atoms, and (b) branched saturated having 8 to 22 carbon atoms. Fatty acid is 5-40 mol%. When the proportion of the linear saturated fatty acid is more than 95 mol%, the dissolution temperature becomes high and it becomes difficult to produce liposomes, or the dissolution temperature becomes high, so that the dextrin fatty acid ester itself is crystallized in the liposome composition. When the proportion of the branched fatty acid is more than 40 mol%, the effect of suppressing crystallization of ceramides is not noticeable.

[Dextrin part of dextrin fatty acid ester]
The dextrin used in the dextrin fatty acid ester of the present invention is a compound in which α-glucose is polymerized by a glycosidic bond, and in the present invention obtained by hydrolysis of starch, the average degree of polymerization of glucose is 3 to 150, 10 to 100 dextrin is particularly preferable. When the average polymerization degree of glucose is 2 or less, the obtained dextrin ester becomes wax-like and the solubility is lowered. On the other hand, when the average degree of polymerization of glucose exceeds 150, problems such as an increase in the melting temperature of the dextrin fatty acid ester or poor solubility may occur. The sugar chain of dextrin may be linear, branched or cyclic.
The average degree of polymerization of glucose in the dextrin part is determined by measuring the reducing sugar by the Somogy-Nelson method and the total sugar by the phenol-sulfuric acid method using glucose as a standard (quantitative method for reducing sugar, published by the Academic Publishing Center). Calculated.
Average degree of polymerization of glucose = total sugar (mass%) / reducing sugar (mass%)

  Conventionally, various dextrin fatty acid esters that can be contained in cosmetics, external preparations for skin, and the like have been known. The dextrin fatty acid ester that is excellent in the effect of suppressing crystallization of the ceramides of the present invention is specified as described above. It is characterized by having a structure. The component (B) can be produced, for example, according to the production method shown in Japanese Patent No. 3019191, but can also be obtained as a commercial product. For example, as a commercially available product, the substitution degree of fatty acid per glucose unit is 1.6, the fatty acid portion is 87 mol% of straight chain fatty acid palmitic acid, and 13 mol of 2-ethylhexanoic acid which is a branched fatty acid having 8 carbon atoms. % Dextrin fatty acid ester having an average degree of polymerization of 30; Leopard TT2 (manufactured by Chiba Flour Milling Co., Ltd.).

  The content of the component (B) in the liposome composition of the present invention is preferably 0.002 to 4%, more preferably 0.02 to 2%. Within this range, a liposome composition capable of suppressing crystallization of ceramides and containing ceramides stably can be obtained.

  The esterified product of the component (B) dextrin and fatty acid has a high anti-crystallization effect on the ceramides of the component (A), and also imparts the storage stability of the liposome composition in the present invention. The content ratio of the components (A) and (B) is preferably in the range of (A) / (B) = 0.48 to 1, and (A) / (B) = 0.5 is particularly preferable. Within this range, crystallization of ceramides can be suppressed and ceramides can be stably contained, and a liposome composition excellent in storage stability, rough skin improvement effect and moisturizing effect can be obtained.

  The phospholipid of component (C) used in the present invention has a structure in which a fatty acid and a phosphoric acid are combined with glycerin or sphingosine as a central skeleton, and an alcohol is ester-bonded to the phosphoric acid, unless otherwise specified. Say. Examples of the fatty acid constituting the phospholipid include saturated and unsaturated carboxylic acids having 7 to 22 carbon atoms. The alcohol constituting the phospholipid often contains nitrogen, and examples thereof include choline, ethanolamine, inositol, and serine.

  The phospholipid of the component (C) of the present invention is contained as a main component for forming the lipid bilayer membrane of the liposome composition. In addition, the moisturizing effect of the phospholipid itself can synergize with the ceramides to impart a rough skin improving effect and a moisturizing effect to the liposome composition of the present invention. Such a phospholipid is not particularly limited as long as it is used in normal cosmetics, for example, soybean-derived phospholipid, soybean-derived hydrogenated phospholipid, soybean-derived lysophospholipid, soybean-derived hydrogenated lysophospholipid, Egg yolk-derived phospholipids, egg yolk-derived hydrogenated phospholipids, egg yolk-derived lysophospholipids, egg yolk-derived hydrogenated lysophospholipids can be mentioned, and these phospholipids can be used singly or in combination of two or more as necessary. Examples include soybean-derived hydrogenated phospholipid, soybean-derived hydrogenated lysophospholipid, egg yolk-derived hydrogenated phospholipid, and egg yolk-derived hydrogenated lysophospholipid. These phospholipids can be used singly or in combination of two or more as required.

  0.004-8% is preferable and, as for content of the component (C) in the liposome composition of this invention, it is more preferable that it is 0.04-4%. Within this range, a liposome composition having excellent storage stability and moisturizing effect can be obtained.

  The phospholipid of the component (C) is one in which the ceramide of the component (A) is encapsulated in the lipid bilayer membrane of the liposome composition in the present invention, but the content mass ratio of the components (A) and (C) is , (A) / (C) = 0.04 to 0.27 is preferable, and (A) / (C) = 0.04 to 0.16 is particularly preferable. Within this range, ceramide can be amorphously contained and stably contained, and a liposome composition excellent in storage stability, rough skin improvement effect and moisturizing effect can be obtained.

  The component (D) cholesterol or phytosterol of the present invention constitutes a lipid bilayer together with the component (C). Component (D) contributes to the stability of the lipid bilayer structure, and is preferable in that it can improve the storage stability of the liposome when combined. Cholesterol and phytosterol can be used in combination of two or more as required.

  The content of component (D) in the liposome composition of the present invention is preferably 0.0008 to 1.6%, more preferably 0.008 to 0.8%. Within this range, the lipid bilayer membrane can be stabilized and a liposome composition having excellent storage stability can be obtained.

  The component (D) cholesterol or phytosterol is also made non-crystallized by the esterified product of the component (B) dextrin and fatty acid, and imparts improved storage stability of the liposome composition of the present invention. The mass ratio of B) and (D) is preferably in the range of (B) / (D) = 0.2 to 1.5, and (B) / (D) = 0.2 to 0.85. The range of is particularly preferable. Within this range, cholesterol or phytosterol can be made amorphous to further stabilize the lipid bilayer, and a liposome composition excellent in storage stability, rough skin improvement effect and moisturizing effect can be obtained.

  Component (E) in the liposome composition of the present invention is a higher alcohol having a branch having 18 to 24 carbon atoms, an ester of a fatty acid having 8 to 18 carbon atoms and a monohydric alcohol having 2 to 16 carbon atoms, or 8 to 18 carbon atoms. Esters of fatty acids and dihydric alcohols having 2 to 16 carbon atoms are those that contain both ceramide of component (A) and esterified products of dextrin and fatty acids of component (B) as components that improve the moisturizing effect. It is. Such component (E) is not particularly limited as long as it is used in ordinary cosmetics. Examples of higher alcohols having a branch having 18 to 24 carbon atoms include isostearyl alcohol and 2-octyldodeca And 2-decyltetradecanol, an ester of a fatty acid having 8 to 18 carbon atoms and a monohydric alcohol having 2 to 16 carbon atoms, a fatty acid having 8 to 18 carbon atoms and a divalent having 2 to 16 carbon atoms. Examples of the ester with alcohol include isopropyl myristate, isononyl isononanoate, ethyl oleate, and dipentyl glycol di-2-ethylhexanoate. One or more of these can be used.

  The mass ratio of components (C) and (E) in the liposome composition of the present invention is preferably in the range of (C) / (E) = 10 to 50, and (C) / (E) = 20 to A range of 50 is particularly preferred. Within this range, cholesterol or phytosterol can be made amorphous to further stabilize the lipid bilayer, and a liposome composition excellent in storage stability, rough skin improvement effect and moisturizing effect can be obtained.

[Water phase]
The composition of the present invention is a liposome composition forming a lipid bilayer, and water is used as a medium for an aqueous phase. Water is a medium in the inner phase of the lipid bilayer and also a medium in the outer phase of the lipid bilayer. Water can give a fresh feel to the skin during and after use.

  The water that can be used is not particularly limited as long as it is acceptable as a cosmetic or an external preparation for skin. For example, in addition to purified water, hard water, soft water, natural water, tap water, seawater, deep ocean water, electrolysis Alkaline ion water, electrolytic acid ion water, ion water, and cluster water can be used. The content of water is not particularly limited, and can be appropriately contained according to the amount of other components.

[Other ingredients]
In addition to the above components, the liposome composition of the present invention can contain various components. In particular, by containing a polyhydric alcohol, a more excellent external preparation for skin can be obtained in terms of storage stability and usability. The polyhydric alcohol that can be used in the present invention is not particularly limited. For example, propylene glycol, 1,3-butylene glycol, dipropylene glycol, 1,2-pentanediol, glycerin, diglycerin, sorbitol, or the like is used. Can do. Of these, dipropylene glycol and glycerin are particularly preferable.

  In the liposome composition of the present invention, a pH adjusting agent may be used. When the pH of the composition exceeds 8, the phospholipid used may be hydrolyzed and the stability of the vesicle state composed of the lipid bilayer membrane may not be sufficient. The pH adjuster is not particularly limited as long as it can adjust the pH of the composition to 5.0 to 8.0 and is acceptable as a component for external use on the skin. Examples of pH adjusting agents that can be used in the present invention include citrate, phosphate, and tartrate. In addition, when mentioning pH by this invention, it is a value at the time of 25 degreeC except the case where it describes especially.

  The liposomal composition of the present invention can contain an oil agent as long as the oil agent other than the aforementioned component (E) is smaller than the content of the component (E). The oil can soften the skin and exert an action of imparting a moist feeling to the skin.

  As the oil used in the present invention, the origin of animal oils, vegetable oils, synthetic oils and the like commonly used in cosmetics and the properties of solid oils, semi-solid oils, liquid oils, volatile oils, hydrocarbons, Fats, waxes, hardened oils, ester oils, fatty acids, silicone oils, fluorine oils, lanolin derivatives, oily gelling agents, lipophilic surfactants, oil-soluble UV absorbers, etc. Is mentioned. Specifically, hydrocarbons such as liquid paraffin, squalane, petrolatum, polyisobutylene, polybutene, paraffin wax, ceresin wax, microcrystalline wax, montan wax, fish trops wax, olive oil, castor oil, jojoba oil, mink oil , Vegetable oils such as macadamian nut oil, beeswax, carnauba wax, candelilla wax, waxes such as gay wax, owl, cetyl isooctanoate, isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, glyceryl trioctanoate, Polyglyceryl diisostearate, diglyceryl triisostearate, glyceryl tribehenate, pentaerythritol ester of rosin acid, neopentyl glycol dioctanoate, Esters of terol fatty acid esters, N-lauroyl-L-glutamic acid di (cholesteryl, behenyl, octyldodecyl), fatty acids such as stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, rosin acid, Silicones such as low polymerization dimethylpolysiloxane, high polymerization dimethylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, polyether-modified polysiloxane, cross-linked organopolysiloxane, fluorine-modified silicone Fluorine oils such as perfluoropolyether, perfluorodecane, perfluorooctane, lanolin derivatives such as lanolin, lanolin acetate, lanolin fatty acid isopropyl, lanolin alcohol, Oily gelling agents such as string fatty acid ester, sucrose fatty acid ester, starch fatty acid ester, 12-hydroxystearic acid, aluminum stearate, calcium stearate, lipophilicity such as glyceryl monostearate, sorbitan tristearate, sorbitan sesquioleate Surfactants, ethyl paraaminobenzoate, paramethoxycinnamate-2-ethylhexyl, oil-soluble UV absorbers such as 4-tert-butyl-4'-methoxydibenzoylmethane, oxybenzone, and the like Can be used singly or in combination of two or more.

  In addition to the essential components described above, the liposome composition of the present invention includes components used in ordinary cosmetics, such as water-soluble polymers, alcohols, aqueous components, surfactants, powders, ultraviolet absorbers, Moisturizers, antioxidants, beauty agents for the purpose of whitening and antioxidants, preservatives, fragrances, refreshing agents and the like can be contained within a range not impairing the effects of the present invention.

  Examples of whitening agents include arbutin, vitamin C and its derivatives, hawthorn extract, Inchinkou (Kawara mugwort) extract, licorice extract, Clara extract, wheat extract, saicin extract, rice and rice bran extract, black Examples include currant extract, Ibukitorano extract, Neubara (Agetsu) extract, Ezocogi extract, Sakuhakuhi extract, Toki extract, coffee extract, pearl barley (Yokuinin) extract and the like.

  Antioxidants include coenzyme Q10, alpha lipoic acid, vitamin E and derivatives thereof, carotenoids, dibutylhydroxytoluene, butylhydroxyanisole, rutin and derivatives thereof, glutathione and derivatives thereof, superoxide dismutase, mannitol, caquette extract, geno shoco Extract, Peonies extract, Superoxide Dismutase, Ginkgo biloba extract, Scarab (Ogon) extract, Mikaika (Maikai, Hermanus) extract, Tormentilla extract, Grape extract, Yashajitsu (Yasha) extract, Yukinoshita extract, Examples include rosemary (mannenro) extract, tea extract (Oolong tea, black tea, green tea, etc.) and the like.

  Furthermore, the liposome composition of the present invention can also contain an electrolyte. Specifically, for example, glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, threonine, serine, proline, hydroxyproline, tryptophan, thyroxine, methionine, cystine, cysteine, aspartic acid, glutamic acid, asparagine, glutamine, lysine , Amino acids such as arginine and histidine and water-soluble derivatives of amino acids such as trimethylglycine and N-acetyl-glutamic acid, hydroxyacetic acid, lactic acid, β-hydroxypropionic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, α-hydroxy Isocaproic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, fumaric acid, maleic acid, malic acid, tartronic acid, citric acid, tartaric acid Sodium salt such as pyrrolidonecarboxylic acid, potassium salt, triethanolamine salt, ammonium salt, dipotassium glycyrrhizinate, urea, L-ascorbic acid-2-sodium phosphate, L-ascorbic acid-2-magnesium phosphate, ascorbic acid glucoside , Phenylbenzimidazole sulfonate, and hydroxymethoxybenzophenone sulfonate. It is more preferable that the content of the electrolyte is 0.1 to 5% in terms of cosmetic effects and stability at high temperatures.

  For the production of the liposome composition of the present invention, conventional methods known to those skilled in the art can be used. Although not particularly limited, for example, the components (A), (B), (C), (D), and (E) are heated in advance and mixed uniformly, and heated while stirring there. Add the aqueous components. Here, the formation of the lipid bilayer membrane can be confirmed by performing the obtained agent and observing the presence of a Maltese cross image under a polarized nicols under a polarizing microscope. Subsequently, this is subjected to high-pressure treatment, and another aqueous system is added and mixed.

  The particle size of the liposome composition of the present invention is not particularly limited, but is preferably 100 to 400 nm, more preferably 150 to 350 nm from the viewpoint of stability over time. Such a liposome composition of the present invention may have a transparent to translucent appearance. In addition, the particle size here is a value measured by a Coulter counter (Beckman Coulter, Inc .: submicron particle analyzer N5).

  The liposome composition of the present invention can be used as it is, but is suitable for use by adding the liposome composition of the present invention to cosmetics or external preparations for skin. The amount of the liposome composition when used by adding to a cosmetic or external skin preparation is not particularly limited, but can be, for example, 0.1 to 70% with respect to the total amount of the cosmetic or external skin preparation. 0.5 to 60% is preferable, and 1.0 to 50% is more preferable. It is because it can contain stably if it is this range.

  There is no particular limitation on the form of the cosmetic or external preparation for skin obtained by the present invention (including the case where it is a liposome composition itself and the cosmetic or external preparation for skin containing the liposome composition), For example, skin care cosmetics such as skin lotions, milky lotions, creams, eye creams, beauty liquids, massages, packs, hand creams, body creams and the like, and makeup base cosmetics can be exemplified. Moreover, the usage method includes a method of using by hand and fingers, a method of using it by impregnating a nonwoven fabric and the like.

Hereinafter, the present invention will be described in more detail with reference to examples. Note that these do not limit the present invention.
The compositions of the present invention products 1 to 22 and comparative products 1 to 5 shown in Tables 1 to 4 below were prepared. As the confirmation of liposome formation of the obtained composition, the presence or absence of lipid bilayer membrane by maltese cloth formation, the presence or absence of ceramide crystals, the rough skin improvement effect, the moisturizing effect were evaluated by the following methods, and the results are shown in Tables 1 to It is shown in Table 4. In the present invention, since the dissolved state of ceramides changes due to temperature change, not only the stability evaluation at 50 ° C for 1 month storage but also the cycle temperature for 1 month storage (-10 ° C, 10 ° C each) The stability was also evaluated in a cycle in which the temperature was changed every 48 hours.
In Tables 1 to 4, “−” in the evaluation results represents a state in which poor liposome formation or ceramide crystal precipitation was observed, and observation over time was omitted.

[Preparation method]
Components (A), (B), (C), (D), (E) and dipropylene glycol are heated to 100 ° C. and dissolved uniformly. To this, purified water heated to 80 ° C. is added and stirred at 2000 rpm for 3 minutes.
After cooling to room temperature and confirming the presence of a Maltese cross image with a polarizing microscope under crossed Nicols, a high-pressure treatment (800 MPa × 2 times) was performed with a microfluidizer to obtain a liposome composition.

[Evaluation method]
Determined by an expert according to the following. In addition, the presence or absence of liposome formation and ceramide crystals depends on the evaluation using a polarizing microscope.
Liposome formation evaluation Maltese cross image (evaluation before high-pressure treatment)
Each sample of the product before the high-pressure treatment was observed under polarized light using an upright microscope (manufactured by Olympus) at a magnification of 400 times and an exposure time of 1/200 seconds to confirm the presence of a Maltese cross image. .
◎: Observed in all vesicles ○: Observed in most vesicles △: Observed in some vesicles ×: Not observed at all
Presence or absence of ceramide crystals (evaluation before high-pressure treatment, storage stability evaluation)
Immediately after production, each sample stored in a thermostat at 50 ° C. and −10 to 10 ° C. (48 hours cycle) for 1 month was erected by an upright microscope (manufactured by Olympus) at a magnification of 400 times and an exposure time of 1/200 sec. ) Was observed under polarized light. Under polarized light, when ceramides are present as crystals in the composition, they are observed as white glitters. Even if it is not a crystal glitter, when crystallization is progressing, it is observed as a gray-tone image as an unclear ceramide glitter by a microscope.
In addition, when the criterion of each table is “−”, it means that the ceramide crystal glitter is observed immediately after the production, and thus observation with time is omitted.
◎: No ceramide crystal glitter is observed ○: Obscure ceramide crystal glitter is observed △: Small ceramide crystal glitter is partially observed ×: Clear ceramide Crystal glitter is observed
Evaluation of liposome storage stability Immediately after production, the average particle diameter of the liposomes of each sample stored in a thermostat at 50 ° C. and −10 to 10 ° C. (48 hours cycle) for 1 month was calculated using a Coulter counter (manufactured by Beckman Coulter, Inc.). : Measured by a submicron particle analyzer N5), and the rate of change in average particle diameter was evaluated according to the following criteria based on immediately after production.
In addition, when the criterion of each table is “−”, it means omission of observation over time because of poor liposome formation immediately after production.
◎: Change rate of average particle size is less than ± 25% ○: Change rate of average particle size is ± 25% or more and less than ± 50% Δ: Change rate of average particle size is ± 50% or more and less than ± 75% X: Change rate of average particle diameter is ± 75% or more
The rough skin improvement effect test was carried out by 5 healthy persons. The funnel trumpet is pressed against the inner side of the forearm, and about 5 mL of a mixed solution of acetone and diethyl ether in a mass ratio of 1: 1 is poured from the funnel portion with a pasteur so that the skin is completely immersed. Leave it for 20 minutes to create artificially rough skin. Intercellular lipids, which are barrier constituents in the skin, are soluted by the solution, and the amount of moisture transpiration of the skin increases as the barrier function decreases, and the result can be measured as TEWL (transepidermal water transpiration). it can. The TEWL immediately after creating rough skin was acclimatized for 20 minutes in a constant environment of temperature 22 ° C and relative humidity 50%, and then measured for each panel at 5 points with VapoMeter (manufactured by Delfin), and the average value was calculated. To do. After preparing rough skin, each sample of Examples and Comparative Examples was applied twice in the morning and evening, and the TEWL after 1 week was measured under the same conditions and method as described above. The average TEWL is calculated as a relative value, and the rough skin improvement effect is evaluated.
◎: Recovered relative to initial TEWL less than 90 ○: Recovered relative to initial TEWL 90 to less than 95 Δ: Recovered relative to initial TEWL 95 to less than 100 ×: Relative value 100 relative to initial TEWL Recovery
The moisturizing effect test was conducted with 5 healthy persons. First, after measuring the initial moisture content of the skin on which no sample is applied on the inner side of the forearm with 5 panels on each panel with SKICON-200EX (manufactured by IBI S Co., Ltd.) Similarly, the skin moisture content 24 hours after application is measured in 5 points. When the moisture content of the initial average value is 100, the average moisture content after 24 hours is calculated as a relative value, and the moisturizing effect is evaluated.
A: Relative value average moisture content is 150% or more with respect to initial moisture content B: Relative value average moisture content is less than 150% with respect to initial moisture content 130% or more Δ: Relative value average moisture content with respect to initial moisture content Is less than 130% and 110% or more.

  As is clear from the results of Tables 1 to 4, the present invention products 1 to 22 according to the present invention are encapsulated stabilized liposomes in which ceramide crystals are suppressed, and have excellent transdermal absorbability possessed by the liposomes. Thus, ceramides are supplied to the inside of the skin, and the effect of improving rough skin can be sufficiently exerted. Furthermore, it is possible to sufficiently exhibit the moisturizing effect inherent in phospholipids, cholesterol / phytosterols, ceramides and specific oils. In Comparative Product 1, in the system using dicocoylethylhydroxyethylmonium methosulfate, which is a cation, instead of the phospholipid of component (A), the storage stability of vesicles is poor and the storage stability of liposomes themselves is poor. The ceramides are soluted in the aqueous system and are observed as bright crystals. Moreover, as inferred from the viewpoint of cation skin safety, the skin roughening effect and the moisturizing effect were inferior. Comparative product 2 from which the component (D) cholesterol was removed could not produce liposomes containing ceramides. Comparative product 3 from which the ceramide of component (A) was removed was relatively excellent in the storage stability of liposomes, but did not show a good effect on improving rough skin. In Comparative product 4 in which the specific dextrin fatty acid ester contained in the present invention of component (B) was removed, since ceramide is not non-crystallized, liposomes are hardly formed immediately after production, and in storage over time The liposome structure was completely lost. Furthermore, no favorable skin roughening effect was observed due to the absence of liposomes and the non-crystallization of ceramide. In comparative product 5 using dextrin palmitate similar to the specific dextrin fatty acid ester contained in the present invention of component (B), ceramides crystallized when stored over time, and ceramides were completely non-crystallized. Therefore, even when a liposome carrier was used, the percutaneous absorbability into the skin was inferior, and a good skin roughness improving effect was not seen.

[Example 2: lotion]
(Ingredient) (%)
1. Ceramide 2 (* 2) 0.05
2. (palmitic acid / 2-ethylhexanoic acid) dextrin
Average degree of polymerization 30 Fatty acid substitution rate 1.6
Palmitic acid: 2-ethylhexanoic acid = 87: 13 (* 3) 0.05
3. Hydrogenated soybean lysophospholipid (* 5) 0.2
4). Ethyl oleate 0.01
(Ester of C18 fatty acid and C2 monohydric alcohol)
5. Dipropylene glycol 2
6). Purified water 10
7.1,3-Butylene glycol 20
8). Methyl paraoxybenzoate 0.1
9. Quince seed extract 1
10. Purified water remaining * 5 HP70H (Nippon Seika Co., Ltd.)

A lotion was prepared by the following manufacturing method (manufacturing method).
A: Components (1) to (5) are heated to 100 ° C. and mixed uniformly.
B: Component (6) is heated to 80 ° C.
C: B is gradually added to A and dispersed with a despa mixer.
D: C is cooled to room temperature and subjected to high pressure treatment with a microfluidizer.
E: D was mixed with components (7) to (10) to obtain a skin lotion.

  The skin lotion of Example 2 is an encapsulated stabilized liposome in which crystals of ceramide are suppressed, and the ceramide is supplied to the inside of the skin due to the excellent percutaneous absorption ability of the liposome, and the effect of improving rough skin is sufficiently exhibited. It was possible. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, ceramides and specific oils can be sufficiently exhibited.

[Example 3: Liposome serum]
(Ingredient) (%)
1. Hydrogenated soybean phospholipid (* 6) 0.8
2. Phytosterol 0.2
3. (Palmitic acid / 2-ethylhexanoic acid) dextrin
Average degree of polymerization 30 Fatty acid substitution rate 1.6
Palmitic acid: 2-ethylhexanoic acid = 87:13 * 3 0.05
4). Ceramide 1 (* 7) 0.05
5. Dipropylene glycol 5.0
6). Purified water 50.0
7.1,3-Butylene glycol 7.0
8). Xanthan gum 0.1
9. Sorbitan sesquioleate 0.1
10. Ethanol 5.0
11. Sodium lactate 0.3
12 Polyoxyethylene (60) hydrogenated castor oil 0.2
13. Glycerin 5.0
14 Methyl paraoxybenzoate 0.1
15. Serine 0.1
16. Edetate disodium 0.02
17. Citric acid 3Na 0.25
18. 1 hydrogen phosphate 2Na 0.05
19. Water-soluble collagen 0.01
20. Purified water remaining amount 21. Fragrance 0.05
* 6 HSL-70 YMC Co., Ltd. * 7 Ceramide I Wako Pure Chemical Industries (manufacturing method)
A: Components (1) to (5) are dissolved by heating at 100 ° C.
B: Component (6) is heated to 80 ° C.
C: B is gradually added to A and dispersed with a despa mixer.
D: C is cooled to room temperature and subjected to high pressure treatment with a microfluidizer.
E: Components (7) to (21) were added to and mixed with D to obtain a liposome-type cosmetic liquid.

  The cosmetic liquid of Example 3 is an encapsulated stabilized liposome in which the crystals of ceramides are suppressed, and the ceramides are supplied to the inside of the skin due to the excellent percutaneous absorption ability of the liposomes, so that the effect of improving rough skin is sufficiently exhibited. It was possible. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, and ceramides can be sufficiently exhibited.

[Example 4: Oil-in-water emulsion containing liposome composition]
(Ingredient) (%)
1. Squalane 3.0
2. Dimethylpolysiloxane (20 mm ² / m) 1.0
3. Polyoxyethylene (60) hydrogenated castor oil 1.5
4). Cetostearyl alcohol 0.3
5. Liposome-type serum 15.0 produced with the product 3 of the present invention
6). Dipropylene glycol 7.0
7). Glycerin 5.0
8). Acrylic acid-alkyl methacrylate copolymer (* 8) 0.1
9. Methyl paraoxybenzoate Appropriate amount10. Sodium hydroxide 0.03
11. Edetate disodium 0.02
12 Purified water remaining amount 13. Perfume proper amount * 8 Pemulen TR-2 (manufactured by NOVEON)
(Production method)
A: Components (1) to (4) are heated and mixed at 70 ° C.
B: Components (6) to (12) are heated and mixed at 70 ° C.
C: After emulsifying B in A with stirring with a disper mixer, the mixture was cooled to room temperature, and components (5) and (13) were added and mixed to obtain an emulsion.

  The oil-in-water emulsion of Example 4 contains encapsulated stabilized liposomes in which crystals of ceramides are suppressed, and the ceramides are supplied to the inside of the skin due to the excellent transdermal absorbability of the liposomes, resulting in rough skin. The improvement effect could be fully exhibited. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, and ceramides can be sufficiently exhibited.

[Example 5: Sheet cosmetic]
(Ingredient) (%)
1. Hydrogenated egg yolk lecithin (* 9) 1.6
2. Cholesterol 0.4
3. (Palmitic acid / 2-ethylhexanoic acid) dextrin Average polymerization degree 30 Fatty acid substitution rate 1.6
Palmitic acid: 2-ethylhexanoic acid = 87: 13 (* 3) 0.02
4). Ceramide 3 (* 10) 0.2
5. Dipropylene glycol 5.0
6). Purified water 20.0
7). Ethanol 10.0
8). Tetra 2-ethylhexanoic acid pentaerythritol 0.01
9. Polyoxyethylene (40) hydrogenated castor oil 0.01
10. Polyoxyethylene (60) hydrogenated castor oil 0.01
11. Sorbitan sesquioleate 0.01
12 Polyoxyethylene cetyl ether phosphoric acid 0.006
13. Polyoxyethylene stearyl ether phosphate 0.004
14 Polyoxypropylene diglyceryl ether 0.1
15.1,3-butylene glycol 5.0
16. Methyl paraoxybenzoate 0.1
17. Edetate disodium 0.3
18. Citric acid 3Na 0.25
19. 1 hydrogen phosphate 2Na 0.05
20. Sodium hyaluronate 0.01
21. Tranexamic acid 2.0
22. Carboxyvinyl polymer 0.2
23. Sodium hydroxide 0.06
24. Purified water remaining amount 25. Fragrance 0.1
* 9 Powdered egg yolk lecithin R-20 manufactured by Asahi Kasei Corporation * 10 CERAMIDE3 manufactured by Cosmo Farm (manufacturing method)
A: Components (1) to (5) are dissolved by heating at 100 ° C.
B: Component (6) is heated to 80 ° C.
C: B is gradually added to A and dispersed with a despa mixer.
D: C is cooled to room temperature and subjected to high pressure treatment with a microfluidizer.
E: Components (7) to (25) are added to D, and this is impregnated into the nonwoven fabric.
F: E was hermetically filled in an aluminum laminate bag-like container to obtain a sheet-like cosmetic.

  The sheet-form cosmetic of Example 5 contains encapsulated stabilized liposomes in which ceramide crystals are suppressed, and the ceramides are supplied to the inside of the skin due to the excellent percutaneous absorption ability of the liposomes. The improvement effect could be fully exhibited. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, and ceramides can be sufficiently exhibited.

[Example 6: Oil-in-water cream containing liposome composition]
(Ingredient) (%)
1. Stearic acid 3.0
2. Cetostearyl alcohol 3.0
3. Glyceryl monostearate 1.5
4). Squalane 20.0
5. Vaseline 5.0
6). Glycerin 7.0
7.1,3-Butylene glycol 5.0
8). Liposome composition produced with the product 17 of the present invention 30.0
9. Sodium lactate 0.2
10. Xanthan gum 0.5
11. Phenoxyethanol 0.2
12 Sodium hydroxide 0.1
13. Edetate disodium 0.02
14 Purified water remaining amount 15. Fragrance 0.2
(Production method)
A: Components (1) to (5) are heated and mixed at 70 ° C.
B: Components (6), (7) and (9) to (14) are heated and mixed at 70 ° C.
C: After emulsifying B in A with stirring with a disper mixer, the mixture was cooled to room temperature, and components (8) and (15) were added and mixed to obtain a cream.

  The oil-in-water cream of Example 6 contains encapsulated stabilized liposomes in which crystals of ceramides are suppressed, and the ceramides are supplied to the inside of the skin due to the excellent transdermal absorbability of the liposomes, resulting in rough skin. The improvement effect could be fully exhibited. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, and ceramides can be sufficiently exhibited.

[Example 7: Oil-in-water cream base cosmetic]
(Ingredient) (%)
1. Titanium oxide (particle size 200nm) 2.0
2. Dimethylpolysiloxane (6cs) 15.0
3. Polyoxyethylene (30) cholesteryl ether 1.0
4). Octyl palmitate 1.5
5. Stearyl-modified acrylate silicone * 11 2.0
6). 6. Purified water remaining amount Ethanol 5.0
8). Propylene glycol 5.0
9. Silica powder 2.0
10. Methyl paraoxybenzoate 0.2
11. Fragrance 0.2
12 Soybean-derived hydrogenated phospholipids 2.0
13. Oleic acid 1.0
14 Cholesterol 0.5
15.1,3-butylene glycol 2.0
16. Liposome composition-type cosmetic liquid produced with the present invention product 20.0
* 11 KP-561 Shin-Etsu Chemical Co., Ltd. (manufacturing method)
A: Components (1) to (5) are dispersed by a three-roll mill and then heated to 75 ° C.
B: Components (6) to (15) are uniformly mixed and then heated to 75 ° C.
C: After emulsifying B with stirring with a disper mixer, the mixture was cooled to room temperature, mixed with component (16) to obtain an oil-in-water cream base cosmetic.

  The oil-in-water cream base of Example 7 contains encapsulated stabilized liposomes in which crystals of ceramides are suppressed, and the ceramides are supplied to the inside of the skin due to the excellent transdermal absorbability of the liposomes. The skin roughening effect can be fully exhibited. Furthermore, the moisturizing effect originally possessed by phospholipids, cholesterol / phytosterols, and ceramides can be sufficiently exhibited.

  As described in detail above, ceramides can be non-crystallized and encapsulated in liposomes, so they are excellent in storage stability, and the skin is rough due to the transdermal absorbability of liposomes encapsulating non-crystallized ceramides. The effect of improving the barrier function can be sufficiently exhibited up to the inside of the stratum corneum of the skin.

Claims (8)

The following components (A) to (D);
(A) Ceramides (B) Dextrin fatty acid ester satisfying the following conditions (1) to (3) (1) The degree of substitution of the fatty acid per glucose unit is 1.4 to 1.8 (2) The fatty acid The composition is (a) a linear saturated fatty acid having 12 to 22 carbon atoms and (b) a branched saturated fatty acid having 8 to 22 carbon atoms, and the molar ratio of (a) and (b) is 60:40 to 95: (3) A liposome composition comprising (C) phospholipid (D) cholesterol or phytosterol, wherein the average degree of polymerization of glucose in the dextrin moiety is 3 to 150.   2. The liposome composition according to claim 1, wherein the component (B) is a dextrin ester of (a) palmitic acid and (b) 2-ethylhexanoic acid.   The liposomal composition according to claim 1 or 2, wherein the component (A) is one or more selected from natural ceramides, sphingophospholipids, glycosphingolipids, and phytosphingoglycolipids.   The liposome composition according to any one of claims 1 to 3, wherein the content ratio of the components (A) and (B) is (A) / (B) = 0.48 to 1. .   The liposome composition according to any one of claims 1 to 4, wherein the mass ratio of the components (A) and (C) is (A) / (C) 0.04 to 0.27. object.   Furthermore, the component (E) a higher alcohol having 18 to 24 carbon atoms, an ester of a fatty acid having 8 to 18 carbon atoms and a monohydric alcohol having 2 to 16 carbon atoms, a fatty acid having 8 to 18 carbon atoms and 2 to 2 carbon atoms. The liposome composition according to any one of claims 1 to 5, comprising an oil selected from 16 esters with dihydric alcohols.   The liposome composition according to any one of claims 1 to 6, which is a cosmetic. It is a skin external preparation, The liposome composition in any one of Claims 1-6 characterized by the above-mentioned.