JP2011183309A - Polymersome and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a polymersome composition that has dry rough skin improvement effect, safety, use feeling, particularly gives no feeling of stickiness, good smoothness of skin, and is excellent in base agent stability. <P>SOLUTION: The polymersome principally includes as a membrane component a blocked type alkylene oxide derivative shown by the formula (I): Y-[O(EO)a-(AO)b-(EO)c-R]k, wherein Y is a residue excluding the hydroxy group of polyhydric alcohol having 3-6 hydroxy groups, k is the number of the polyhydric alcohols, EO is an oxyethylene group, AO is a 3-6C oxyalkylene, and each is added in a blocked form, and a×k, b×k, and c×k are the average addition mole numbers of an oxyalkylene, a 3-6C oxyalkylene group and an oxyethylene group, respectively, and have the relations: 0≤a×k≤100, 1≤b×k≤100, and 0≤c×k≤100, and (a+c)×k>1, and wherein the ratio of all the oxyethylene groups in formula (I) to the sum of all the oxyethylene groups and 3-6C oxyalkylene groups in formula (I) is 10-80 mass%, and R is a 1-4C hydrocarbon. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a polymersome and a production method, and more particularly to improvement of its base stability, skin irritation and use feeling.

  When a drug is microencapsulated and administered in vivo, the metabolism of the drug in vivo is suppressed and the medicinal properties can be maintained over a long period of time. Therefore, the active ingredient is microencapsulated in the fields of medicine, cosmetics, food, etc. Various technologies are being sought. One of these is the so-called vesicle. A vesicle is a closed vesicle having a bilayer structure formed by an amphiphile, and because of its specific structure, it can contain an active ingredient, and is attracting attention as a carrier for drug delivery systems and the like. .

  Many amphipathic substances constituting vesicles have been studied, and in particular, vesicles composed of phospholipids derived from living bodies are called liposomes, and various studies have been made from the viewpoint of safety to living bodies. For example, there is a report in which this phospholipid and a specific cationic surfactant are combined to form a vesicle dispersion and applied to cosmetics (see, for example, Patent Document 1). However, since the liposome components are mainly derived from nature, there are many restrictions in terms of stability over time, such as being susceptible to the influence of pH, temperature, and electrolyte.

  There are also many reports on synthetic surfactants as another amphiphilic substance constituting vesicles. For example, Patent Document 2 discloses a technique using a mono (long chain aliphatic) tri (short chain alkyl) ammonium salt, a di (long chain aliphatic) di (short chain alkyl) ammonium salt, and a higher alcohol. . In recent years, vesicle compositions using multi-chain polyhydrophilic surfactants have been studied (see Patent Document 3).

  However, in the technique of Patent Document 2 relating to hair cosmetics, depending on the amount of the cationic surfactant, skin safety may not be preferable. Furthermore, the technique of Patent Document 3 makes it possible to obtain a vesicle by a simple method using an amino acid surfactant, but the stability of the vesicle with time is insufficient.

By the way, in particular, vesicles in which at least one block is hydrophobic and at least one block is hydrophilic, amphiphilic diblocks and multiblock copolymers as amphiphiles are called “polymersomes”. It has been attracting attention that it exhibits superior mechanical stability and unique chemical properties compared to other liposomes and micelles (see, for example, Non-Patent Document 1 and Non-Patent Document 2).
Polymersomes can be stably prepared by many techniques common to liposomes (see, for example, Non-Patent Document 3). Moreover, multi-micron giant vesicles and monodisperse vesicles having a diameter of 100 nanometers can be obtained by film rehydration, sonication, and release.

  In addition to encapsulating water-soluble hydrophilic compounds (drugs, vitamins, fluorophores, etc.) inside their aqueous cavities, polymersomes can also have the ability to encapsulate hydrophobic molecules in thick lamellar membranes. Are known. In addition, the size, film thickness, and stability of their synthetic vesicles choose between block copolymer chemical structure, number average molecular weight, hydrophilic to hydrophobic volume fraction, and through various formulation methods. Can be reasonably adjusted. Accordingly, the polymersome can be provided with many attractive features that are expected to be applied to various uses in medical images, drug delivery, and cosmetic devices (see, for example, Non-Patent Document 4).

  Certain vesicles of PEO-PEE (polyethylene oxide-polyethylethylene) or PEO-PBD (polyethylene oxide-polybutadiene) have a film thickness (eg, about 100 nm thick) that shows improved stability compared to liposomes. It is known to form asome. For example, PEO-PEE diblock copolymers introduced by Hillmeyer and Bates (see Non-Patent Document 5), in particular EO 40-EE 37 (named OE7, EO is an ethylene oxide monomer and EE is an ethylethylene monomer) Has been reported to form a very thick membrane as compared with any natural lipid membrane and exhibit greater mechanical stability (see Non-Patent Document 6).

JP 2006-193461 A JP 2006-104142 A JP 2006-290894 A Science, 2002, 297, 967-973. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2005, 102, 2922-2927. E. Biotechnol. Bioeng. 2001, 73, 135-145 Journal of Controlled Release, 2005, 101, 187-198. Macromolecules, 1996, 29, 6994-7002. Science, 1999, 284, 1143-1164.

However, all vesicles generally have an unstable structure, and there is a problem that it is very difficult to provide stability in long-term storage necessary for cosmetics and pharmaceuticals.
When applying a surfactant to a vesicle, the stability can be expected to improve slightly by adjusting the type and amount of the vesicle, but the same component may contribute to rough skin and the feeling of use may be insufficient. there were. Further, in recent years, higher safety has been demanded for external preparations for skin, and the formulation of surfactants into preparations itself can be problematic. That is, the surfactant is an indispensable component for improving the stability of the base, but it has been virtually impossible to make the improvement of stability completely compatible with the skin safety and the feeling of use.

The amphiphilic copolymer constituting the polymersome is considered to have high stability and safety because it has a higher molecular weight than a conventional surfactant. However, monomers may remain in these copolymers depending on the production method, and there remains a problem with safety when applied to the skin. Furthermore, the polymersomes composed of these amphiphilic copolymers have a problem that the feeling of use on the skin and hair is poor. That is, even in the conventional polymersome, it was impossible to achieve both the stability of the base, the skin safety and the feeling of use.
The present invention has been made in view of the above-mentioned problems, and aims to provide a polymersome that is safe, feels to use, has no particular stickiness, has a smooth skin, and has excellent base stability. To do.

As a result of investigations by the present inventors in order to achieve the above object, the polymersome formed by the alkylene oxide derivative having a specific structure has excellent base stability and exhibits an effect of improving rough skin. It has been found that it has safety and a smooth feeling of use without stickiness. Furthermore, the present inventors have found that it is possible to blend a large amount of low molecular weight and high polarity oils, which have been difficult to be blended into an aqueous base, into the polymersome, and have completed the present invention. It was.
That is, the polymersome according to the present invention uses a block-type alkylene oxide derivative represented by the following formula (I) as a membrane component.

(Chemical formula 1)
Y- [O (EO) a- (AO) b- (EO) c-R] k (I)
(In the formula, Y is a residue obtained by removing a hydroxyl group of a polyhydric alcohol having 3 to 6 hydroxyl groups, k is the number of hydroxyl groups of the polyhydric alcohol, EO is an oxyethylene group, and AO is an oxy of 3 to 6 carbon atoms. Each of which is added in the form of a block with an alkylene group, wherein a × k, b × k and c × k are the average number of moles of oxyethylene group, oxyalkylene group having 3 to 6 carbon atoms, and oxyethylene group, 0 ≦ a × k ≦ 100, 1 ≦ b × k ≦ 100, 0 ≦ c × k ≦ 100, where (a + c) × k> 1 In the formula (I), all oxyethylene groups and 3 to 3 carbon atoms The ratio of all oxyethylene groups in formula (I) to the total of 6 oxyalkylene groups is 10 to 80% by mass, and R is a hydrocarbon group having 1 to 4 carbon atoms.

In the polymersome, it is preferable that the AO group of the block-type alkylene oxide derivative represented by the formula (I) is an oxybutylene group.
In the polymersome, a in the block-type alkylene oxide derivative represented by the formula (I) is 0, and the addition order of AO and EO is (AO)-(EO) with respect to Y in the formula. It is preferable that
In the polymersome, it is preferable to enclose a water-soluble component in the internal pores.
In the polymersome, it is preferable to retain an oily component in the lamellar structure.
In the polymersome, it is preferable that the oil component contains a low molecular oil component and / or a highly polar oil component.
The external preparation for skin according to the present invention includes the polymersome.

Furthermore, the method for producing a polymersome according to the present invention includes the following steps (a) and (b).
(A) A step of mixing the block-type alkylene oxide derivative represented by the above formula (I) and a water-soluble alcohol.
(B) The process of dripping the said liquid mixture to an aqueous solvent, stirring.
In addition, in the production method, in the step (a), the blending amount of the block-type alkylene oxide derivative is preferably 0.1 to 20% by mass, and the blending amount of the water-soluble alcohol is preferably 0.1 to 50% by mass. It is.
In the production method, it is preferable that an oil component is further mixed in the step (a).
Moreover, it is suitable for the said manufacturing method that the compounding quantity of an oil-based component is 0.05-30 mass%.

  According to the present invention, the use of a block-type alkylene oxide derivative having a specific structure has an effect of improving skin roughness, safety, feeling of use, no particular stickiness, smooth skin, and stable base. Polymersomes with excellent properties can be obtained by a simple method. In addition, since the polymersome of the present invention can contain a large amount of low molecular weight and high polarity oil, which has been difficult to be incorporated into an aqueous base, it has a new function and feel for pharmaceuticals, cosmetics, foods, etc. It is possible to grant.

The polymersome according to the present invention is formed of a block-type alkylene oxide derivative having a specific structure and uses this as a membrane component.
The block-type alkylene oxide derivative constituting the polymersome of the present invention has a specific structure represented by the following formula (I).
(Chemical formula 2)
Y- [O (EO) a- (AO) b- (EO) c-R] k (I)

  In the alkylene oxide derivative represented by the above formula (I), Y is a residue excluding the hydroxyl group of the polyhydric alcohol having 3 to 6 hydroxyl groups, k is the number of hydroxyl groups of the polyhydric alcohol, and 3 to 6 It is. Examples of the compound having 3 to 6 hydroxyl groups include glycerin with k = 3, trimethylolpropane, hexylene glycol, erythritol with k = 4, pentaerythritol, xylitol with k = 5, sorbitol with k = 6 And inositol. The block-type alkylene oxide derivative used for the polymersome according to the present invention has, as a basic skeleton, a residue obtained by removing one or a mixture of two or more polyhydric alcohols having 3 to 6 hydroxyl groups.

  In the present invention, Y is more preferably a residue obtained by removing a hydroxyl group of a polyhydric alcohol having 3 to 4 hydroxyl groups, that is, it is preferable that 3 ≦ k ≦ 4 is satisfied. When k is 2 or less, the smoothness of the skin after using the polymersome tends to be inferior, and when k is 7 or more, a sticky feeling tends to occur.

  EO is an oxyethylene group having 2 carbon atoms. AO is an oxyalkylene group having 3 to 6 carbon atoms, and specific examples include an oxypropylene group, an oxybutylene group, an oxyisobutylene group, an oxy t-butylene group, an oxypentylene group, and an oxyhexylene group. . Preferred are an oxypropylene group and an oxybutylene group, and more preferred is an oxybutylene group.

  b × k is the average added mole number of AO, and 1 ≦ b × k ≦ 100, preferably 3 ≦ b × k ≦ 70. a × k and c × k are average added moles of EO, 0 ≦ a × k ≦ 100, 0 ≦ c × k ≦ 100, preferably 3 ≦ a × k ≦ 70, 3 ≦ c × k ≦ 70. Moreover, the preferable range of the average addition mole number of all the oxyethylene groups in the said formula (I) is 1 <(a + c) * k <= 200, More preferably, it is 6 <= (a + c) * k <= 140. AO becomes a hydrophobic site in the block-type alkylene oxide derivative according to the present invention, and when b × k is 0, it tends to be inferior in stability of polymersomes, and when it exceeds 100, it tends to be inferior in smoothness after use. is there. Moreover, when (a + c) × k is 0, the stability of the polymersome tends to be inferior, and when it exceeds 100, a sticky feeling tends to occur.

The ratio of the total EO in the said formula (I) with respect to the sum total of AO and EO in the said formula (I) is 10-80 mass%, More preferably, it is 20-70 mass%. If it is less than 10% by mass, it tends to be inferior in smoothness after use, and if it is more than 80% by mass, it tends to cause stickiness. On the other hand, if the amount is less than 10% by mass, the hydrophilic property of the block-type alkylene oxide derivative is insufficient, and if it is more than 80% by mass, the lipophilicity of the block-type alkylene oxide derivative is insufficient and the target polymersome may not be formed or formed. In some cases, the stability may be insufficient.
Moreover, it is preferable that the molecular weight of an alkylene oxide derivative is 800-5000. If the molecular weight is too small or too large, a sufficient amount of polymersomes may not be obtained, and the feeling in use may decrease.
Moreover, the addition form of AO and EO is a block form from a viewpoint of polymersome formation. The order of addition may be any of the order of (AO)-(EO), (EO)-(AO), and (EO)-(AO)-(EO) with respect to Y in the formula. Good. In the present invention, the order of (AO)-(EO) with respect to Y in the formula is particularly preferable. In the order of (AO)-(EO) with respect to Y in the formula, it corresponds to a in the formula being 0.

  R is a hydrocarbon group having 1 to 4 carbon atoms. Examples of the hydrocarbon group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, and a tert-butyl group. It is done. In the present invention, a methyl group and an ethyl group are preferable. If the carbon number is greater than 5, the moisture retention effect, rough skin improvement effect or base stability tends to be inferior. In the block-type alkylene oxide derivative used for the polymersome according to the present invention, R may be the same or different in one molecule, and the block-type alkylene oxide derivative 1 having the same R in one molecule. It may be a seed or a mixture of two or more having different Rs.

  Specific examples of block-type alkylene oxide derivatives that can be used in the present invention include POB (15) POE (15) glyceryl trimethyl ether, POB (18) POE (18) glyceryl trimethyl ether, POB (18) POE (20) glyceryl trimethyl. Ether, POB (20) POE (22) glyceryl trimethyl ether, POB (25) POE (28) glyceryl trimethyl ether, POB (30) POE (30) glyceryl trimethyl ether, POB (30) POE (35) glyceryl trimethyl ether, POB (17) POE (28) glyceryl trimethyl ether, POB (27) POE (45) glyceryl trimethyl ether, POB (14) POE (34) glyceryl trimethyl ether, POB (22) PO (55) Glyceryl trimethyl ether, POB (19) POE (55) glyceryl trimethyl ether, POB (40) POE (80) glyceryl trimethyl ether, POB (80) POE (40) glyceryl trimethyl ether, POB (30) POE (30) ) Glyceryl triethyl ether, POB (30) POE (35) glyceryl triethyl ether, POB (14) POE (34) glyceryl triethyl ether, POB (30) POE (30) glyceryl tripropyl ether, POE (30) POP (30) Examples thereof include glyceryl trimethyl ether, POE (35) POP (40) glyceryl trimethyl ether, POE (41) POP (48) glyceryl trimethyl ether, and the like.

  The POE, POP, and POB are abbreviations for polyoxyethylene, polyoxypropylene, and polyoxybutylene, respectively, and may be abbreviated as follows. The number of moles added of POE, POP, and POB is expressed as the total number of moles added in the molecule, that is, (a + c) × k, b × k.

  Such a block-type alkylene oxide derivative can be produced by a known method. For example, it is obtained by subjecting a polyhydric alcohol having a hydroxyl group to addition polymerization of ethylene oxide and an alkylene oxide having 3 to 6 carbon atoms, and then subjecting an alkyl halide to an ether reaction in the presence of an alkali catalyst.

Next, the manufacturing method of the polymersome concerning this invention is demonstrated.
The polymersome according to the present invention is produced as a polymersome composition by thoroughly mixing the block-type alkylene oxide derivative having the above specific structure with a water-soluble alcohol, and then dropping the mixture into an aqueous solvent while stirring. be able to.
The mixed state of the block-type alkylene oxide derivative and the water-soluble alcohol only needs to confirm that the mixed solution is in a transparent one-phase state, and this is achieved, for example, by mixing at room temperature to 90 ° C. for about 1 to 30 minutes. can do.

  In the production method according to the present invention, the blending amount of the block-type alkylene oxide derivative is 0.1 to 20% by mass, more preferably 0.1 to 10% by mass with respect to the finally produced polymersome composition. is there. When the blending amount of the block-type alkylene oxide derivative is less than 0.1% by mass, the effect of the blending may not be sufficiently exhibited, and when it exceeds 20% by mass, a sticky feeling may occur. Moreover, it is preferable to set the compounding quantity of water-soluble alcohol so that it may become 0.1-50 mass% with respect to a polymersome composition.

  Examples of the water-soluble alcohol include lower alcohols, polyhydric alcohols, polyhydric alcohol polymers, dihydric alcohol alkyl ethers, dihydric alcohol alkyl ethers, dihydric alcohol ether esters, glycerin monoalkyl ethers, sugar alcohols, simple alcohols. Examples thereof include sugars, oligosaccharides, polysaccharides, and derivatives thereof, and one or more of these can be used.

  Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

  Examples of the polyhydric alcohol include divalent alcohols (for example, dipropylene glycol, 1,3-butylene glycol, ethylene glycol, trimethylene glycol, 1,2-butylene glycol, tetramethylene glycol, and 2,3-butylene glycol. , Pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trivalent alcohol (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohol (eg, diglycerin, 1 , 2,6-hexanetriol, etc.); pentavalent alcohol (eg, xylitol, triglycerin, etc.); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol) , Dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, triglycerin, tetraglycerin, polyglycerin, etc.); divalent alcohol alkyl ethers (for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether) , Ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether , Ethylene glycol di Divalent alcohol alkyl ethers (for example, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol) Monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene Dihydric alcohol ether ester (for example, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diazebate, ethylene glycol disuccine) Diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); glycerin monoalkyl ether Sugars (eg, maltotriose, erythritol, glucose, fructose, amylolytic sugar, maltose, amylolytic sugar reducing alcohol, etc.) Tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP / POE-butyl ether tripolyoxypropylene glycerin ether; POP-glycerin ether; POP-glycerin ether phosphate; POP / POE- Examples include pentane erythritol ether and polyglycerin.

  Examples of monosaccharides include tricarbon sugars (eg, D-glyceryl aldehyde, dihydroxyacetone, etc.); tetracarbon sugars (eg, D-erythrose, D-erythrose, D-threoose, erythritol, etc.) Pentoses (eg, L-arabinose, D-xylos, L-lyxose, D-arabinose, D-ribose, D-ribose, D-xylulose, L; -Xylose, etc .; hexose (eg, D-glucose, D-talose, D-psicose, D-galactose, D-fructose, L-galactose, L -Mannose, D-tagatose, etc.); heptose sugar (eg, aldoheptose, heproose, etc.); octose sugar (eg, octrose, etc.); deoxy sugar (eg, 2-deoxy- D-ribose, 6-deoxy-L-galactose, 6-deoxy-L Amino sugars (eg, D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.); uronic acids (eg, D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid, L-iduronic acid and the like).

  Examples of the oligosaccharide include sucrose, gnocyanose, umbelliferose, lactose, planteose, isolicnose, α, α-trehalose, raffinose, lycnose, umbilicin, stachyose, verbose course and the like.

  Examples of the polysaccharide include cellulose, quince seed, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate-tragacanth gum, keratan sulfate, chondroitin, xanthan gum, guar gum, dextran, kerato sulfate, locust bean gum, succinoglucan, etc. Is mentioned.

Other polyols include polyoxyethylene methyl glucoside (Glucam E-10), polyoxypropylene methyl glucoside (Glucam P-10) and the like.

In the production method of the polymersome composition of the present invention, the aqueous solvent represents water (for example, purified water, ion exchange water, tap water, etc.) or an aqueous solution of a water-soluble component, and the aqueous phase component in the system It corresponds to.
Examples of the water-soluble component include additives such as powders, humectants, thickeners, and preservatives that are usually blended in cosmetics and quasi drugs. In addition, when blending a water-soluble component with a high melting point, it can be pre-heated and uniformly dissolved in water. However, after the water-soluble component is dissolved, the aqueous solution is returned to room temperature and then the polymersome is produced. It is desirable to use it.

  In addition, since the internal pores of the polymersome formed in the aqueous solvent by the production method are filled with the aqueous solvent that is a dispersion medium of the polymersome, a drug or the like as a water-soluble component is dispersed or dissolved in the aqueous solvent. It is also possible to produce polymersomes in which the component is encapsulated in the internal pores. These water-soluble components can also be introduced into internal vacancies by generating polymersomes and then adding them to an aqueous solvent, or by dispersing the polymersomes generated in an aqueous solution of water-soluble components prepared at an appropriate concentration. It may be possible.

Furthermore, the polymersome concerning this invention can mix | blend the oil component normally difficult to mix with a water phase component stably by hold | maintaining an oil-based component in the lamellar structure. In addition, it is thought that the creation of products with new properties and functions will be possible by setting a wide range of oil content.
Retaining the oil component in the polymersome is achieved by adding and mixing the oily component to be retained between the membranes when mixing the block-type alkylene oxide derivative and the water-soluble alcohol in the polymersome production method. can do.
The blending amount of the oil component is preferably set to 0.05 to 30% by mass with respect to the finally obtained polymersome composition.

The oil component to be retained in the polymersome of the present invention includes hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicone oils, liquid fats, solid fats, waxes, etc. that are usually used in cosmetics, quasi drugs, etc. 1 type, or 2 or more types of oily components can be used.
In particular, the polymersome of the present invention makes it possible to stably mix a large amount of a low molecular oil component or a high polarity oil component, which has been difficult to mix with an aqueous phase component. Here, the low molecular oil component is an oil component having a molecular weight of 500 or less, and the high polar oil component is an oil component having an IOB value of 0.15 or more. The IOB value refers to the ratio of the inorganic value (IV) to the organic value (OV) in the organic conceptual diagram, that is, “inorganic value (IV) / organic value (OV)”. An organic conceptual diagram is based on methane (CH ₄ ) as the source of all organic compounds, and all other compounds as derivatives of methane. Set and add the scores to obtain the organic and inorganic values, and plot them on a diagram with the organic value on the X axis and the inorganic value on the Y axis ("Organic Conceptual Diagram" -Fundamentals and Applications "(by Yoshio Koda, Sankyo Publishing, 1984), etc.).
In addition, as described above, since various oily components can be blended in a wide range of amounts, by setting the blending species and amount, for example, various kinds according to desired use feelings and functions such as a moisturizing effect and a rough skin preventing effect. New polymersomes can be produced.

  Examples of hydrocarbon oils include liquid paraffin, dodecane, isododecane, tetradecane, isotetradecane, hexadecane, isohexadecane, eicosene, isoeicosene, tridecane, tetradecane, hydrogenated polyisobutylene, docosane, ozokerite, squalane, pristane, paraffin, ceresin, squalene. , Petrolatum, microcrystalline wax and the like.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, toluic acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) ) And the like.

  Examples of higher alcohols include linear alcohols (eg, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol); branched chain alcohols (eg, monostearyl glycerin ether (batyl alcohol)) -2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyl decanol, isostearyl alcohol, octyldodecanol, etc.).

  Synthetic ester oils include, for example, isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, lactic acid Myristyl, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, monoisostearate N-alkyl glycol, neopentyl glycol dicaprate, Tripropylene glycol pivalate, diisostearyl malate, glycerin di-2-heptylundecanoate, diisostearate Lysine, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylolpropane, tetra-2-ethylhexanoic acid pentaerythritol, tri-2-ethylhexanoic acid glycerin, trioctanoic acid glycerin, triisopalmitic acid glycerin, tri Trimethylolpropane isostearate, cetyl 2-ethylhexanoate-2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleyl oleate, acetoglyceride, palmitic acid 2 -Heptylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl Laurate, di-2-ethylhexyl sebacate, myristic acid 2-hexyl decyl palmitate, 2-hexyldecyl, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, and triethyl citrate.

  Examples of the silicone oil include linear polysiloxanes (for example, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane); cyclic polysiloxanes (for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexa Siloxane etc.) Silicone resin, silicone rubber, various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc.), acrylic silicones forming a three-dimensional network structure Etc.

  Examples of liquid oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern castor oil, castor oil, linseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin and the like.

  Examples of the solid fat include cacao butter, palm oil, horse fat, hydrogenated palm oil, palm oil, beef tallow, sheep fat, hydrogenated beef tallow, palm kernel oil, pork fat, beef bone fat, owl kernel oil, hydrogenated oil, cattle Leg fats, moles, hydrogenated castor oil and the like.

  Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugarcane wax, lanolin fatty acid isopropyl, hexyl laurate, and reduced lanolin. Jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, and the like.

By the production method, the polymersome can be obtained as a polymersome composition dispersed in an aqueous solvent. Such a polymersome can be suitably used as a component of cosmetics or pharmaceuticals in the form of the composition. Of course, if possible, polymersomes dispersed in an aqueous solvent may be isolated and used.
In particular, when the polymersome or polymersome composition according to the present invention is incorporated into a known cosmetic / pharmaceutical base, a skin external preparation excellent in safety, feel in use, and base stability can be obtained. .
In addition, the skin external preparation containing polymersomes is a component generally used for skin external preparations usually used in cosmetics and quasi-drugs in the polymersome production method, for example, ionic surfactants, nonionic surfactants, Thickeners, etc., and water powders such as inorganic pigments and extender pigments, moisturizers, UV absorbers, chelating agents, preservatives, dyes, and fragrances in an aqueous phase as long as the effects of the present invention are not impaired. Or it can manufacture also by mix | blending suitably in an oil phase.

  Anionic surfactants include, for example, fatty acid soaps (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (eg, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosine acid (eg, sodium lauroyl sarcosine, etc.); higher fatty acid amide sulfonate (eg, sodium N-myristoyl-N-methyl taurate, palm Oil fatty acid methyl tauride sodium, lauryl methyl tauride sodium, etc .; phosphate ester salt (POE-oleyl ether sodium phosphate, POE-stearyl ether phosphate, etc.); sulfosuccinate (eg, Sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc .; alkyl benzene sulfonates (eg, sodium linear dodecyl benzene sulfonate, triso linear dodecyl benzene sulfonate) Ethanolamine, linear dodecyl benzene sulfonic acid, etc.); higher fatty acid ester sulfates (for example, hydrogenated coconut oil fatty acid sodium glycerin sulfate, etc.); N-acyl glutamate (for example, monosodium N-lauroyl glutamate, di-N-stearoyl glutamate) Sodium, N-myristoyl-L-monosodium glutamate, etc.); sulfated oil (eg funnel oil); POE-A Kill ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; higher fatty acid ester sulfonate; secondary alcohol sulfate ester; higher fatty acid alkylolamide sulfate ester; lauroyl monoethanolamide succinic acid Sodium; N-palmitoyl aspartate ditriethanolamine; sodium caseinate and the like.

  Examples of the cationic surfactant include quaternary ammonium salts such as cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, behenyldimethylhydroxyethylammonium chloride, stearyldimethylbenzylammonium chloride, and cetyltriethylammonium methylsulfate. Is mentioned. Also, stearic acid diethylaminoethylamide, stearic acid dimethylaminoethylamide, palmitic acid diethylaminoethylamide, palmitic acid dimethylaminoethylamide, myristic acid diethylaminoethylamide, myristic acid dimethylaminoethylamide, behenic acid diethylaminoethylamide, behenic acid dimethyl Aminoethylamide, stearic acid diethylaminopropylamide, stearic acid dimethylaminopropylamide, palmitic acid diethylaminopropylamide, palmitic acid dimethylaminopropylamide, myristic acid diethylaminopropylamide, myristic acid dimethylaminopropylamide, behenic acid diethylaminopropylamide, behenine Amidoamino such as dimethylaminopropylamide Compounds.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (for example, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt, etc.); betaine surfactants (for example, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine) , Sulfobetaine, etc.).

  Examples of the lipophilic nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, Sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexyl); glycerin polyglycerin fatty acids (for example, mono-cotton oil fatty acid glycerin, mono-erucic acid glycerin, sesquioleate glycerin, monostearin) Glycerin acid, α, α′-oleic acid pyroglutamate glycerin, monostearate glycerin malate, etc.); propylene glycol fatty acid esters (for example, And propylene glycol monostearate); hardened castor oil derivatives; glycerin alkyl ethers and the like.

Examples of the hydrophilic nonionic surfactant include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan trioleate, POE-sorbitan tetraoleate, etc.); POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE-glycerin) Monostearate, POE-glycerol monoisostearate, POE-monooleate such as POE-glycerol triisostearate, etc.); POE-fatty acid esters (for example, POE-distearate, P E-monodiolate, ethylene glycol distearate, etc.); POE-alkyl ethers (for example, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-core) Stanol ether, etc.); Pluronic type (for example, Pluronic, etc.); POE • POP-alkyl ethers (for example, POE • POP-cetyl ether, POE • POP-2-decyltetradecyl ether, POE • POP-monobutyl ether, POE / POP-hydrogenated lanolin, POE / POP-glycerin ether, etc.); Tetra POE / tetra-POP-ethylenediamine condensates (for example, Tetronic, etc.); POE-castor oil hardened castor oil derivative For example, POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, POE-hardened castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearic acid diester, POE-hardened castor Oil maleic acid, etc.); POE-beeswax lanolin derivatives (eg POE-sorbite beeswax etc.); alkanolamides (eg coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide etc.); POE-propylene glycol fatty acid Examples include ester; POE-alkylamine; POE-fatty acid amide; sucrose fatty acid ester; alkylethoxydimethylamine oxide-trioleyl phosphate.

  Examples of thickeners include gum arabic, carrageenan, caraya gum, gum tragacanth, carob gum, quince seed (malmello), casein, dextrin, gelatin, sodium pectate, sodium alginate, methyl cellulose, ethyl cellulose, CMC, hydroxyethyl cellulose, hydroxypropyl Cellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, cellulose dialkyldimethylammonium sulfate, xanthan gum, magnesium aluminum silicate, bentonite, hectorite, silicate A1Mg (bee gum) Examples thereof include laponite and silicic anhydride.

  Examples of natural water-soluble polymers include plant-based polymers (for example, gum arabic, tragacanth gum, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, quince seed (malmello), alge colloid (guckweed extract), starch (Rice, corn, potato, wheat), glycyrrhizic acid); microbial polymers (eg, xanthan gum, dextran, succinoglucan, bullulan, etc.); animal polymers (eg, collagen, casein, albumin, gelatin, etc.), etc. Is mentioned.

  Semi-synthetic water-soluble polymers include, for example, starch polymers (eg, carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose polymers (methylcellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate) Hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, cellulose powder and the like); alginic acid polymers (for example, sodium alginate, propylene glycol alginate, etc.) and the like.

  Synthetic water-soluble polymers include, for example, vinyl polymers (eg, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer); polyoxyethylene polymers (eg, polyethylene glycol 20,000, 40). Acrylic polymer (for example, sodium polyacrylate, polyethyl acrylate, polyacrylamide, etc.); polyethyleneimine; cationic polymer, and the like.

  Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, sericite (sericite), muscovite, phlogopite, synthetic mica, saucite, biotite, permiculite, magnesium carbonate, calcium carbonate, Aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, Ceramic powder, metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate), boron nitride, etc .; organic powder (eg, polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, Styrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder, etc.); inorganic white pigment (eg, titanium dioxide, zinc oxide, etc.); inorganic red pigment (eg, , Iron oxide (Bengara), iron titanate, etc.); inorganic brown pigment (for example, γ-iron oxide, etc.); inorganic yellow pigment (for example, yellow iron oxide, loess); inorganic black pigment (for example, black) Iron oxide, low-order titanium oxide, etc.); inorganic purple pigments (eg, mango violet, cobalt violet, etc.); inorganic green pigments (eg, chromium oxide, chromium hydroxide, cobalt titanate, etc.); inorganic blue pigments (eg, For example, ultramarine, bitumen, etc .; pearl pigments (eg, titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated tar) , Colored titanium oxide coated mica, bismuth oxychloride, fish scale foil, etc.); metal powder pigments (eg, aluminum powder, copper powder, etc.); organic pigments such as zirconium, barium or aluminum lake (eg, red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401, Blue 404, etc. Organic pigment, Red No. 3, Red No. 104, Red No. 106, Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203 , Green No. 3 and Blue No. 1 etc.); natural pigments (eg chlorophyll, β-carotene etc.) and the like.

  Examples of the humectant include propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, Examples thereof include sodium lactate, bile salt, DL-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO adduct, Izayoi rose extract, yarrow extract, and merirot extract.

Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers (for example, paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester. N, N-dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA ethyl ester, etc.); anthranilic acid ultraviolet absorbers (for example, homomenthyl-N-acetylanthranylate, etc.); Salicylic acid UV absorbers (eg, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate); (For example, octylcinnamate, ethyl-4-isopropylcinnamate, methyl-2,5-diisopropylcinnamate, ethyl-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, propyl-p-methoxy Cinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate) -2-ethoxyethyl-p-methoxycinnamate, cyclohexyl -p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate-2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate, etc.); Benzo Enon UV absorbers (for example, -2,4-dihydroxybenzophenone-2-2'-dihydroxy-4-methoxybenzophenone-2-2'-dihydroxy-4,4'-dimethoxybenzophenone-2-2 ', 4,4 '
-Tetrahydroxybenzophenone-2-hydroxy-4-methoxybenzophenone-2-hydroxy-4-methoxy-4'-methylbenzophenone-2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone-2- Ethylhexyl-4′-phenyl-benzophenone-2-carboxylate-2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone, etc.); 3- (4′-methylbenzylidene) -d, l -Camphor, 3-benzylidene-d, l-camphor-2-phenyl-5-methylbenzoxazole-2-2'-hydroxy-5-methylphenylbenzotriazole-2- (2'-hydroxy-5'-t -Octylphenyl) benzotriazole-2- (2 '-Hydroxy-5'-methylphenylbenzotriazole;dibenzalazine;dianisoylmethane;4-methoxy-4'-tert-butyldibenzoylmethane; 5- (3,3-dimethyl-2-norbornylidene) -3-pentane-2 -ON etc. are mentioned.

  Examples of the sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, and tetrasodium edetate. Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyl triacetate and the like.

  Examples of amino acids include neutral amino acids (eg, threonine, cysteine, etc.); basic amino acids (eg, hydroxylysine, etc.) and the like. Examples of amino acid derivatives include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione and the like.

  Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, and the like. Is mentioned.

  Examples of the polymer emulsion include an acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin liquid, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

  Examples of the pH adjuster include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.

  Examples of vitamins include vitamins A, B1, B2, B6, C, E and derivatives thereof, pantothenic acid and derivatives thereof, biotin and the like.

Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters and the like.
Examples of the antioxidant assistant include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, and ethylenediaminetetraacetic acid.

  Other ingredients that can be blended include, for example, preservatives (ethyl paraben, butyl paraben, etc.); anti-inflammatory agents (eg, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, etc.); Extract, placenta extract, saxifrage extract, arbutin, etc.); various extracts (eg, buckwheat, auren, shikon, peonies, assembly, birch, sage, loquat, carrot, aloe, mallow), iris, grape, yokuinin, loofah, lily , Saffron, senkyo, ginger, hypericum, onionis, garlic, capsicum, chimpi, toki, seaweed, etc.), activator (for example, royal jelly, photosensitizer, cholesterol derivative, etc.); blood circulation promoter (for example, nonenyl acid valenylamide, nicotine) Acid Gyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, gingerone, cantalis tincture, ictamol, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandrate, cinnarizine, trazoline, acetylcholine, verapamil, cephalanthin , Γ-oryzanol, etc.); antiseborrheic agents (eg, sulfur, thianthol, etc.); anti-inflammatory agents (eg, tranexamic acid, thiotaurine, hypotaurine, etc.) and the like.

  Next, the present invention will be described more specifically with reference to examples. The present invention is not limited thereby. Unless otherwise specified, all blending amounts are shown in mass%.

First, an evaluation method used in each example and comparative example will be described.
Evaluation (1): Polymersome formation ability Whether or not polymersomes (vesicle structure) were formed in each of the obtained samples was determined by the following method. Judgment criteria are as follows.
○: Particles having a size of 50 to 500 nm were confirmed by dynamic light scattering measurement, and inclusion (*) of a water-soluble dye was confirmed by absorbance measurement. Also, no turbidity / precipitation was observed.
X: Vesicle particles of 50 to 500 nm were not confirmed by dynamic light scattering measurement. Or even if it was recognized, turbidity and precipitation were recognized simultaneously.

(*) Encapsulation experiment of water-soluble dye: When preparing the target composition, bromophenol blue, which is a water-soluble dye, was added in addition to the components described under conditions of pH 6 or higher. After the obtained composition was dialyzed, the absorbance of the obtained dialyzate was measured. In the absorbance measurement, when clear absorption is observed at around 600 nm, it can be confirmed that the water-soluble dye is encapsulated, that is, a polymersome (vesicle) structure is formed.
The dynamic light scattering measurement and the inclusion experiment are simple evaluation methods. In addition, the formation of polymersomes and vesicles can be confirmed by confirming the presence or absence of a Maltese cross image by observation with a polarizing microscope or by observation with a transmission electron microscope. It is also possible to confirm.

Evaluation (2): No stickiness The actual use test of each test example was conducted by 10 professional panels on the non-stickiness on the skin during and after use. The evaluation criteria are as follows.
A: Eight or more panelists recognized that there was no stickiness during and after use.
○: 6 or more and less than 8 panelists recognized that there was no stickiness during use and after use.
Δ: 3 or more and less than 6 panelists recognized that there was no stickiness during and after use.
X: Less than 3 panelists recognized that there was no stickiness during use and after use.

Evaluation (3): Smoothness With regard to the smoothness of the skin after use, an actual use test of each test example was conducted by 10 professional panels. The evaluation criteria are as follows.
A: Eight or more panelists recognized that there was smoothness after use.
○: 6 or more and less than 8 panelists recognized that there was smoothness after use.
Δ: 3 or more and less than 6 panelists recognized that there was smoothness after use.
X: Less than 3 panelists recognized that there was smoothness after use.

Evaluation (4): Moisturizing effect feeling With respect to the presence or absence of the moisturizing effect feeling after 120 minutes of use, an actual use test of each test example was carried out by 10 professional panelists. The evaluation criteria are as follows.
A: Eight or more professional panelists recognized that there was a moisturizing effect.
○: 6 or more and less than 8 professional panelists recognized that there was a moisturizing effect.
(Triangle | delta): 3 or more and less than 6 professional panelists recognized having a moisturizing effect feeling.
X: Less than three professional panelists recognized that there was a moisturizing effect.

Evaluation (5): Rough skin improvement effect test The rough skin improvement effect test of each test example was carried out by a panel of 10 people with rough skin on the face (part: cheek). In the test method, different test samples were applied to the left and right cheeks for one week, and the determination was made the next day after the period. The evaluation criteria are as follows.
A: Eight or more panelists recognized that rough skin was improved.
○: 6 or more panelists and less than 8 panelists recognized that rough skin was improved.
Δ: 3 or more and less than 6 panelists recognized that the rough skin was improved.
X: Less than 3 panelists recognized that the rough skin was improved.

Evaluation (6): Skin irritation test A 24-hour occlusion patch was applied to the inner side of the upper arm of 10 panelists, and then the average value was calculated according to the following criteria. The evaluation criteria are as follows.
0: No abnormality is observed at all.
1: Slight redness is observed.
2: Redness is recognized.
3: Redness and papules are observed.
Evaluation criteria for the skin irritation test are as follows.
A: Average value of 10 panel members: 0 or more and less than 0.15 B: Average value of 10 panel members: 0.15 or more and less than 0.2 Δ: Average value of 10 panel members: 0.2 or more and less than 0.3 × ... Average value of 10 panelists: 0.3 or more

Evaluation (7): Base stability For the polymersome composition of each test example, after filling the transparent glass bottle immediately after production and leaving at 50 ° C. for 4 weeks, the base stability was evaluated by visual observation based on the following criteria. Was done.
<Evaluation criteria>
○: Transparent or translucent ×: Cloudiness or separation

  Next, synthesis examples of block-type alkylene oxide derivatives used for production of polymersomes according to the present invention will be shown. Various alkylene oxide derivatives can be produced according to such synthesis examples.

<Synthesis Example 1>
Synthesis of polyoxybutylene (30 mol) polyoxyethylene (30 mol) trimethylglyceryl ether (block type alkylene oxide derivative) 92 g of glycerin and 18 g of potassium hydroxide as a catalyst were charged into the autoclave, and the air in the autoclave was replaced with dry nitrogen. Then, the catalyst was completely dissolved at 140 ° C. with stirring. Next, 2160 g of butylene oxide was dropped with a dropping device and stirred for 2 hours. Subsequently, 1320 g of ethylene oxide was dropped with a dropping device and stirred for 2 hours. Next, 400 g of potassium hydroxide was charged and the inside of the system was replaced with dry nitrogen, and then 300 g of methyl chloride was injected at a temperature of 80 to 130 ° C. and reacted for 5 hours. Thereafter, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid and adjusted to pH 6 to 7, and treated at a reduced pressure of -0.088 MPa (gauge pressure) at 100 ° C. for 1 hour in order to remove the contained water. Further, filtration was performed to remove the salt generated after the treatment, and a block-type alkylene oxide derivative was obtained.
Samples that were sampled and reacted before reacting with methyl chloride had a hydroxyl value of 49, the alkylene oxide derivative 1 had a hydroxyl value of 0.4, and the ratio of the number of hydrogen atoms to the number of terminal methyl groups was 0.008. An atom is converted to a methyl group.

<Synthesis Example 2>
Synthesis of polyoxyethylene (57 mol) trimethylglyceryl ether (alkylene oxide derivative) 92 g of glycerin and 18 g of potassium hydroxide as a catalyst were charged into an autoclave, and the air in the autoclave was replaced with dry nitrogen. The catalyst was completely dissolved. Next, 2508 g of ethylene oxide was dropped with a dropping device and stirred for 2 hours. Next, 400 g of potassium hydroxide was charged and the inside of the system was replaced with dry nitrogen, and then 300 g of methyl chloride was injected at a temperature of 80 to 130 ° C. and reacted for 5 hours. Thereafter, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid and adjusted to pH 6 to 7, and treated at a reduced pressure of -0.088 MPa (gauge pressure) at 100 ° C. for 1 hour in order to remove the contained water. Further, filtration was performed to remove the salt generated after the treatment, and an alkylene oxide derivative was obtained.
Samples which were sampled and reacted before reacting with methyl chloride had a hydroxyl value of 66, and the alkylene oxide derivative 1 had a hydroxyl value of 0.60.009, and the ratio of the number of hydrogen atoms to the number of terminal methyl groups was almost completely hydrogen atoms. Has been converted to a methyl group.

<Synthesis Example 3>
Synthesis of polyoxybutylene (30 mol) polyoxyethylene (30 mol) glyceryl ether (block type alkylene oxide derivative) 92 g of glycerin and 18 g of potassium hydroxide as a catalyst were charged into the autoclave, and the air in the autoclave was replaced with dry nitrogen. Thereafter, the catalyst was completely dissolved at 140 ° C. with stirring. Next, 2160 g of butylene oxide was dropped with a dropping device and stirred for 2 hours. Subsequently, 1320 g of ethylene oxide was dropped with a dropping device and stirred for 2 hours. Thereafter, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid and adjusted to pH 6 to 7, and treated at a reduced pressure of -0.088 MPa (gauge pressure) at 100 ° C. for 1 hour in order to remove the contained water. Further, filtration was performed to remove the salt generated after the treatment, and a block-type alkylene oxide derivative was obtained.

<Synthesis Example 4>
Synthesis of polyoxybutylene (30 mol) polyoxyethylene (30 mol) tributyl glyceryl ether (block type alkylene oxide derivative) 92 g of glycerol and 18 g of potassium hydroxide as a catalyst were charged into the autoclave, and the air in the autoclave was replaced with dry nitrogen. Then, the catalyst was completely dissolved at 140 ° C. with stirring. Next, 2160 g of butylene oxide was dropped with a dropping device and stirred for 2 hours. Subsequently, 1320 g of ethylene oxide was dropped with a dropping device and stirred for 2 hours. Next, after charging 800 g of potassium hydroxide and replacing the inside with dry nitrogen, 1200 g of butyl chloride was injected at a temperature of 80 to 130 ° C. and reacted for 5 hours. Thereafter, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid and adjusted to pH 6 to 7, and treated at a reduced pressure of -0.088 MPa (gauge pressure) at 100 ° C. for 1 hour in order to remove the contained water. Further, filtration was performed to remove the salt generated after the treatment, and a block-type alkylene oxide derivative was obtained.
Samples which were sampled and reacted before reacting with methyl chloride had a hydroxyl value of 50, the alkylene oxide derivative 1 had a hydroxyl value of 1.5, and the ratio of the number of hydrogen atoms to the number of terminal butyl groups was 0.03, indicating that hydrogen was almost completely removed. Atoms are converted to butyl groups.

<Synthesis Example 5>
Synthesis of polyoxybutylene (30 mol) and polyoxyethylene (30 mol) glyceryl ether (random type alkylene oxide derivative) 92 g of glycerin and 18 g of potassium hydroxide as a catalyst were charged into the autoclave, and the air in the autoclave was replaced with dry nitrogen. Thereafter, the catalyst was completely dissolved at 140 ° C. with stirring. Next, a mixture of 2160 g of butylene oxide and 1320 g of ethylene oxide was dropped with a dropping device and stirred for 2 hours. Next, 400 g of potassium hydroxide was charged and the inside of the system was replaced with dry nitrogen, and then 300 g of methyl chloride was injected at a temperature of 80 to 130 ° C. and reacted for 5 hours. Thereafter, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid to adjust to pH 6 to 7, and treated at a reduced pressure of -0.088 MPa (gauge pressure) at 100 ° C for 1 hour in order to remove the contained water. Further, filtration was performed to remove the salt generated after the treatment, and a random alkylene oxide derivative was obtained.

  Samples which were sampled before being reacted with methyl chloride and purified had a hydroxyl value of 47, the resulting random alkylene oxide derivative 5 had a hydroxyl value of 0.5, and the ratio of the number of hydrogen atoms to the number of terminal methyl groups was 0.011. The hydrogen atom is almost completely converted to a methyl group.

The block-type alkylene oxide derivative used in the following test examples has a structure represented by the following formula (II). For example, when b ¹ + b ² + b ³ = 30, c ¹ + c ² + c ³ = 30, (BO) ₃₀ (EO) ₃₀

  First, the polymersome composition of the test example which consists of a mixing | blending composition described in Table 1 was manufactured, and the evaluation test was done about said evaluation (1)-(7).

Manufacturing method (1)-(5) is mixed at room temperature until it becomes a transparent one phase state, The obtained liquid mixture is dripped in the liquid mixture of (6)-(11), stirring, and a composition Got.

As shown in Table 1, Test Example 1-1 using a block-type alkylene oxide derivative formed a polymersome, and obtained excellent evaluation in all of stability, safety, and use feeling.
On the other hand, in Test Examples 1-2 and 1-3 using a general nonionic surfactant in place of the block-type alkylene oxide derivative, formation of polymersomes was not observed, and any evaluation was conducted in Test Example 1. It was inferior to -1. In particular, in Test Example 1-2, the rough skin improving effect and stickiness were poor, and in Test Example 1-3, the base stability tended to be inferior.
From the above, it is clear that the present invention is a polymersome excellent in use feeling, stability and safety obtained by using a block type alkylene oxide derivative having a specific structure as a membrane component.

  Subsequently, the above evaluations (1) to (7) were performed on test examples of the formulations shown in Table 2 below, and an alkylene oxide derivative suitable for the present invention was specified.

The production methods (1) to (12) and (19) are mixed at room temperature until a transparent one-phase state is obtained, and the obtained mixed solution is mixed into the mixed solution of (13) to (18) and (20). The composition was obtained by dropwise addition with stirring.

As shown in Table 2, test examples 2-1 to 2-5, which are block polymers of BO and EO, and R ^{1 to} R ³ are methyl groups, form polymersomes, and exhibit stability, safety, and feel in use. Excellent evaluation was obtained in all of the above.
On the other hand, Test Example 2-6 using an alkylene oxide derivative in which the (EO) a (AO) b (EO) c portion was formed only with an oxyethylene group did not form a polymersome, and improved use feeling and rough skin effect. Test Example 2-7 using an alkylene oxide derivative that is particularly poor in point and having only an oxybutylene group does not form polymersomes, is inferior in use feeling and base stability, and has an effect of improving rough skin and smoothing skin. It was not enough.

  Furthermore, in Test Example 2-8 using a block-type alkylene oxide derivative whose terminal is hydrogen, although polymersomes were formed, it is not preferable in terms of use feeling, rough skin improvement effect and skin irritation. In Test Example 2-9 using a block-type alkylene oxide derivative having a hydrocarbon group having 6 carbon atoms at the end, although polymersomes were formed, it was insufficient in terms of base stability. In addition, Test Example 2-10 using a random alkylene oxide derivative did not form polymersomes and was inferior in base stability.

  As a result of the above results and further studies, in the present invention, a block type alkylene oxide derivative having 3 to 4 carbon oxyalkylene groups and oxyethylene groups, which is an average of oxyalkylene groups and oxyethylene groups The added mole numbers are 1 ≦ b × k ≦ 100 and 1 <(a + c) × k ≦ 200, respectively, and the ratio of the oxyethylene group to the total of the oxyalkylene group having 3 to 4 carbon atoms and the oxyethylene group is 10 to 10. A block-type alkylene oxide derivative which is 80% by mass and R is a hydrocarbon group having 1 to 4 carbon atoms which may be the same or different is preferable.

  Next, in order to investigate a suitable blending amount of the block-type alkylene oxide derivative having a specific structure in the production of the polymersome according to the present invention, a polymersome composition comprising the blending composition described in Table 3 was produced, and the above evaluation ( An evaluation test was performed on 1) to (6).

The production methods (1) to (5) and (11) are mixed at room temperature until a transparent one-phase state is obtained, and the obtained mixed solution is subjected to (6) to (10), (12) and (13). The mixture was added dropwise with stirring to give a composition.

From Table 3, the polymersome according to the present invention has an effect of improving skin roughness in the range of 0.1 to 20% by mass of the block type alkylene oxide derivative having a specific structure, and has excellent safety and use feeling. It has been confirmed that it works. In particular, the moisturizing effect feeling and skin roughness improving effect increased depending on the blending amount of the block type alkylene oxide derivative having a specific structure.
On the other hand, Test Example 3-1, in which the blending amount of the block-type alkylene oxide derivative was 0.01% by mass, did not form polymersomes, and the moisturizing effect and the effect of improving skin roughness were insufficient.

  From the above results, in the present invention, the blending amount of the block-type alkylene oxide derivative having a specific structure is preferably 0.1 to 20% by mass with respect to all the components used for producing the polymersome composition. In particular, the blending amount is more preferably 0.1 to 10% by mass in terms of lack of stickiness and smoothness.

  Next, in order to investigate a suitable blending amount of the water-soluble alcohol in the production of the polymersome according to the present invention, a polymersome composition having the blending composition described in Table 4 was produced, and the above evaluations (1) to (7) ) Was evaluated.

The production methods (1) to (3) and (7) are mixed at room temperature until a transparent one-phase state is obtained, and the obtained mixed solution is subjected to (4) to (6), (8) and (9). The mixture was added dropwise with stirring to give a composition.

As shown in Table 4, Test Examples 4-2 to 4-6, in which 0.1 to 50% by mass of a water-soluble alcohol (dipropylene glycol) was blended with respect to the composition during production, formed polymersomes and used All evaluations of touch, safety, and stability were high.
On the other hand, in Test Example 4-1, which did not contain a water-soluble alcohol, formation of polymersome was not observed, and the base stability was poor. In addition, Test Example 4-7 in which the blending amount of the polyol which is a water-soluble alcohol was 60% by mass was inferior in use feeling such as non-stickiness and smoothness, and some skin irritation was felt. Was insufficient.
From the above results, in the present invention, the blending amount of the water-soluble alcohol is preferably 0.1 to 50% by mass with respect to all the components used for producing the polymersome composition.

  Next, in order to investigate a suitable blending amount of the oil component to be retained in the lamellar structure of the polymersome according to the present invention, a polymersome composition having the blending composition shown in Table 5 was produced and evaluated. In Table 5, regarding the smoothness and moisturizing effect feeling based on Test Example 5-1, “low effect: ×” “same effect: Δ” “highly effective: ○” “very effective” High: indicated by “◎”.

The production methods (1) to (3) and (7) are mixed at room temperature until a transparent one-phase state is obtained, and the obtained mixed solution is subjected to (4) to (6), (8) and (9). The mixture was added dropwise with stirring to give a composition.

Test Examples 5-1 to 5-6 in Table 5 all formed polymersomes and were superior in usability, safety and stability as compared to the case where polymersomes were not formed. Test Examples 5-3 to 5-6 containing 0.05% by mass or more of the component (tripropylene glycol pivalate) have higher results in smoothness and moisturizing effect than Test Example 5-1 containing no oil component. showed that.
On the other hand, as in Test Example 5-1, polymersomes are formed without the addition of oily components, and the effects of polymersomes are exerted. However, the moisturizing effect and skin roughness improving effect of the oily components are inferior to those of the test examples. It was. The oil component showed a relatively high effect with a blending ratio of only 0.01% by mass as in Test Example 5-2, but in order to obtain a higher moisturizing effect in the present invention, a blending ratio of 0.05 to 30% by mass Was considered preferred.

※製造工程
Ａ：ブロック型アルキレンオキシド誘導体、エタノール、トリ−２−エチルヘキサン酸グリセリンおよび香料を秤量・攪拌し、均一透明な混合液を得た。その他の配合成分を十分に溶解させた水相を攪拌しながらこの混合液を滴下し、ポリマーソーム組成物を得た。
Ｂ：すべての配合成分をイオン交換水中に秤量・攪拌することにより、組成物を得た。 Next, in order to investigate the suitable manufacturing process of this polymersome, the polymersome composition which consists of a mixing | blending composition described in Table 6 was manufactured, and the evaluation test was done about said evaluation (1)-(7).

* Production process A: A block-type alkylene oxide derivative, ethanol, glycerin tri-2-ethylhexanoate and a fragrance were weighed and stirred to obtain a uniform transparent mixed solution. While stirring the aqueous phase in which other compounding components were sufficiently dissolved, this mixed solution was dropped to obtain a polymersome composition.
B: A composition was obtained by weighing and stirring all the blended components in ion-exchanged water.

As shown in Table 6, in Test Example 6-1 produced in Step A, an average particle size (about 100 nm) was small, and a polymersome composition having a transparent to translucent appearance was obtained. Evaluations (1) to (7 ) Was excellent in both evaluations.
In Test Example 6-2 produced in Step B, an emulsion composition having a large average particle diameter and a cloudy appearance was obtained, and polymersomes were not formed. The base stability as an emulsion of Test Example 6-2 was remarkably inferior to that of those having polymersomes formed.
Further, in Test Example 6-2, a temporary moisturizing effect and an improvement effect on rough skin were recognized by the addition of the oil component, but since the oil content in the emulsion was insufficiently dispersed, the feeling of use such as stickiness and smoothness was observed. Deterioration was also observed at the same time.

  From the above results, in the production of the polymersome according to the present invention, the block-type alkylene oxide derivative having a specific structure, a part or all of the water-soluble alcohol, and the oil component are sufficiently mixed, and then the mixed solution is mixed with an aqueous solvent. It is preferable to provide a step of dropping while stirring.

  Next, in order to examine the suitable blending amount of the oil component in the present polymersome composition and its effect when compared with the emulsion composition, a polymersome composition comprising the blending composition described in Table 7 was manufactured, Evaluation tests were performed for evaluations (1) to (7).

※製造工程
Ａ：ブロック型アルキレンオキシド誘導体、ジプロピレングリコール、ピバリン酸トリプロピレングリコール、パラメトキシ桂皮酸２−エチルヘキシルおよび香料を秤量・攪拌し、均一透明な混合液を得た。その他の配合成分を十分に溶解させた水相を攪拌しながらこの混合液を滴下し、ポリマーソーム組成物を得た。
Ｃ：ピバリン酸トリプロピレングリコール、パラメトキシ桂皮酸２−エチルヘキシルおよび香料を秤量・攪拌し、均一透明な混合油溶液を得た。ブロック型アルキレンオキシド誘導体およびジプロピレングリコールを含むすべての配合成分をイオン交換水中に十分に溶解させた水相を攪拌しながらこの混合油溶液を徐々に添加し、さらにホモミキサーにて乳化・攪拌し、エマルション組成物を得た。

* Production process A: A block-type alkylene oxide derivative, dipropylene glycol, tripropylene glycol pivalate, 2-ethylhexyl paramethoxycinnamate and a fragrance were weighed and stirred to obtain a uniform transparent mixed solution. While stirring the aqueous phase in which other compounding components were sufficiently dissolved, this mixed solution was dropped to obtain a polymersome composition.
C: Tripropylene glycol pivalate, 2-ethylhexyl paramethoxycinnamate and fragrance were weighed and stirred to obtain a uniform transparent mixed oil solution. The mixed oil solution is gradually added while stirring the aqueous phase in which all the ingredients including the block-type alkylene oxide derivative and dipropylene glycol are sufficiently dissolved in ion-exchanged water, and the mixture is further emulsified and stirred with a homomixer. An emulsion composition was obtained.

As shown in Table 7, in Test Examples 7-1 to 7-3 produced in Step A, a polymersome composition having a transparent to translucent appearance was obtained. For any evaluation of evaluations (1) to (7) Was also excellent. There was a tendency that the moisturizing effect and the effect of improving rough skin were improved by increasing the amount of the blended oil.
On the other hand, in Test Examples 7-4 to 7-6 produced in Step C, emulsion compositions having a cloudy appearance were obtained. All of the blended oils were highly polar oils, and the base stability as an emulsion was extremely inferior. Moreover, although Test Examples 7-4 to 7-6 tended to improve the moisturizing effect and the effect of improving skin roughness by increasing the amount of the blended oil as in the polymer composition, the stability of the emulsion was insufficient. Therefore, the oil content could not be spread uniformly on the skin, and a tendency to be slightly inferior to the effect of the polymersome composition was observed, and further deterioration in the feeling of use such as stickiness and smoothness was simultaneously observed.

  From the above results, in the present invention, by using a polymersome having a block type alkylene oxide derivative having a specific structure as a membrane component, a large amount of highly polar oil that cannot be achieved with an emulsion using the same component is stably blended. In addition, it is clear that an increase in the blending amount of the oil can provide an excellent feeling of use that could not be achieved in the past.

  Although the example of a skin external preparation which mix | blended the polymersome of this invention is given to the following, the technical scope of this invention is not limited by these. The obtained external preparation for skin had good safety and use feeling and high base stability.

Formulation Example 1 Lotion
(mass%)
Ethanol 10
Dipropylene glycol 1
Polyethylene glycol 1000 1
Jojoba oil 0.01
Glyceryl tri-2-ethylhexanoate 0.5
POB (25) POE (28) Trimethyl glyceryl ether 0.95
N-stearoyl-L-glutamate sodium 0.1
Citric acid 0.05
Sodium citrate 0.2
Potassium hydroxide 0.4
Dipotassium glycyrrhizinate 0.1
Arginine hydrochloride 0.1
L-ascorbic acid 2-glucoside 2
Ogon Extract 0.1
Yukinoshita extract 0.1
Nettle extract 0.1
Tranexamic acid 1
Edetate trisodium 0.05
2-Ethylhexyl paramethoxycinnamate 0.01
Preservative Appropriate amount of perfume Appropriate amount of purified water Residue

(Production method)
POB (25) POE (28) Trimethyl glyceryl ether, ethanol, glyceryl tri-2-ethylhexanoate, jojoba oil, 2-ethylhexyl paramethoxycinnamate, and fragrance were weighed and stirred to obtain a uniform transparent mixed solution. While stirring the aqueous phase in which other compounding components were sufficiently dissolved, this mixed solution was dropped to obtain a polymersome composition.

Formulation Example 2 Hairist
(mass%)
Isohexadecane 0.1
Camellia oil 0.3
Ethanol 5
Glycerin 2
Dipropylene glycol 1
1,3-butylene glycol 1
Alkyltrimethylammonium chloride (77%) 0.5
POB (18) POE (20) Trimethyl glyceryl ether 1
Preservative Appropriate amount Purified water Residual fragrance Appropriate amount

(Production method)
POB (18) POE (20) trimethyl glyceryl ether, ethanol, dipropylene glycol, isohexadecane, camellia oil and perfume were weighed and stirred to obtain a uniform transparent mixed solution. While stirring the aqueous phase in which other compounding components were sufficiently dissolved, this mixed solution was dropped to obtain a polymersome composition.

Claims (11)

A polymersome comprising a block-type alkylene oxide derivative represented by the following formula (I) as a membrane component.
(Chemical formula 1)
Y- [O (EO) a- (AO) b- (EO) c-R] k (I)
(In the formula, Y is a residue obtained by removing a hydroxyl group of a polyhydric alcohol having 3 to 6 hydroxyl groups, k is the number of hydroxyl groups of the polyhydric alcohol, EO is an oxyethylene group, and AO is an oxy of 3 to 6 carbon atoms. Each of which is added in the form of a block with an alkylene group, wherein a × k, b × k and c × k are the average number of moles of oxyethylene group, oxyalkylene group having 3 to 6 carbon atoms, and oxyethylene group, 0 ≦ a × k ≦ 100, 1 ≦ b × k ≦ 100, 0 ≦ c × k ≦ 100, where (a + c) × k> 1 In the formula (I), all oxyethylene groups and 3 to 3 carbon atoms The ratio of all oxyethylene groups in formula (I) to the total of 6 oxyalkylene groups is 10 to 80% by mass, and R is a hydrocarbon group having 1 to 4 carbon atoms. The polymersome according to claim 1, wherein the AO group of the block-type alkylene oxide derivative represented by the formula (I) is an oxybutylene group. In the block type alkylene oxide derivative represented by the formula (I), a is 0, and the addition order of AO and EO is (AO)-(EO) with respect to Y in the formula. The polymersome according to claim 1 or 2.   The polymersome according to any one of claims 1 to 3, wherein a water-soluble component is encapsulated in the internal pores.   The polymersome according to any one of claims 1 to 4, wherein an oily component is retained in the lamella structure.   The polymersome according to claim 5, wherein the oily component contains a low molecular oil component and / or a high polar oil component.   An external preparation for skin, comprising the polymersome according to any one of claims 1 to 6. The manufacturing method of the polymersome characterized by including the process of following (a) and (b).
(A) A step of mixing the block-type alkylene oxide derivative represented by the above formula (I) and a water-soluble alcohol.
(B) The process of dripping the said liquid mixture in an aqueous solvent, stirring.   The said (a) process WHEREIN: The compounding quantity of a block-type alkylene oxide derivative is 0.1-20 mass%, and the compounding quantity of water-soluble alcohol is 0.1-50 mass%, It is characterized by the above-mentioned. A method for producing polymersomes.   The method for producing a polymersome according to claim 8 or 9, wherein an oily component is further mixed in the step (a).   The method for producing a polymersome according to claim 10, wherein the blending amount of the oil component is 0.05 to 30% by mass.