JP2008074780A - Method for controlling skin absorption part of liposome, and controlled release agent of liposome skin absorption - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for controlling the skin absorption part of liposome and a controlled release agent of skin absorption of the liposome used in the above method, and further, a skin preparation for external use containing the controlled release agent of skin absorption of the liposome. <P>SOLUTION: This method for controlling the skin absorption-arriving part of the liposome is provided by changing the content of phosphatidylcholine in phospholipid by 0 to 100 mass% in absorbing the liposome containing the phospholipid containing 0 to 100 mass% phosphatidylcholine as a membrane-constituting component into the skin. The controlled release agent of the liposome skin absorption for controlling the skin absorption-arriving part of the liposome consisting of the above liposome is provided. The skin preparation for external use containing the controlled release agent of the liposome skin absorption is also provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for controlling the skin absorption site of liposomes by changing the content of phosphatidylcholine in phospholipids used as membrane constituents of liposomes, and liposomes containing phospholipids of phosphatidylcholine having various contents as membrane constituents. It is related with the skin skin absorption control release agent which consists of.

Liposomes are closed vesicles composed of a lipid bilayer having an aqueous phase inside, and are used mainly as carriers of physiologically active substances in a wide range of fields such as pharmaceuticals and cosmetics.
When encapsulating a physiologically active substance or the like in a liposome and transdermally absorbing it, controlling the target site in the skin depending on the type of the physiologically active substance or the like of the encapsulated substance is effective in effectively exerting the medicinal effect.

  According to Takahashi et al., Hydrogenated soybean lecithin was prepared by increasing the total content of phosphotidylinositol and phosphatidylethanolamine to about 60% in phospholipids commonly used as liposome membranes. When the storage effect in the stratum corneum of tocopherol acetate was examined, it was reported that the effect increased compared with general hydrogenated soybean lecithin. It is explained that this effect is derived from the fact that phosphotidylinositol and phosphotidylethanolamine are more likely to stay in the upper stratum corneum than phosphotidylcholine (see Non-Patent Document 1).

  However, there is no disclosure or suggestion of a technique for controlling the target site in the skin during percutaneous absorption of liposomes. If the target site in the skin at the time of percutaneous absorption can be controlled with high accuracy, it will have high dermatological value.

Fragrance Journal, 2001-12, p. 51

  The present invention has been made in view of the above circumstances, and its object is to provide a method for controlling the skin absorption site of liposomes, a skin absorption control release agent for liposomes used in the method, and a skin absorption control release agent for liposomes. It is in providing the skin external preparation containing.

  As a result of diligent research to solve the above-mentioned problems, the present inventors used a phospholipid containing 0 to 100% by mass of phosphatidylcholine as a membrane constituent of the liposome, and changed the content of phosphatidylcholine in the phospholipid. It is possible to control the skin absorption site of the liposome, and the liposome is found to be a release agent capable of controlling the skin absorption of the liposome by the liposome containing the phospholipid of various contents of phosphatidylcholine as a membrane component, The present invention has been completed.

  That is, the present invention changes the content of phosphatidylcholine in the phospholipid in the range of 0 to 100% by mass when the liposome containing the phospholipid containing 0 to 100% by mass of phosphatidylcholine as a membrane component is absorbed into the skin. It is a method of controlling the skin absorption arrival site | part of the said liposome by carrying out.

  Furthermore, the present invention provides a phospholipid containing 0 to 100% by mass of phosphatidylcholine and a liposome containing one or more selected from the group consisting of a surfactant and a cholesterol ester as a membrane component. It is a method of controlling the skin absorption reaching site of the liposome by changing the content of phosphatidylcholine in the range of 0 to 100% by mass.

  In the above method, when one or more selected from the group consisting of a surfactant and a cholesterol ester are used in combination with a phospholipid as a membrane constituent component of the liposome, the control of the site of liposome absorption through the skin becomes more accurate.

  The surfactant in the method is preferably an acylmethyl taurate salt and / or a polyoxyethylene hydrogenated castor oil.

  The acylmethyl taurine salt in the above method is preferably a methyl stearoyl taurine salt.

  The phospholipid in the above method is preferably a hydrogenated phospholipid.

  Furthermore, the present invention comprises a liposome containing a phospholipid containing 0 to 100% by mass of phosphatidylcholine as a membrane component, and by changing the phosphatidylcholine content in the phospholipid in the range of 0 to 100% by mass, It is a liposome skin absorption control release agent for controlling the site of skin absorption.

  Furthermore, the present invention comprises a phospholipid containing 0-100% by mass of phosphatidylcholine and a phosphatidylcholine in the phospholipid, comprising a liposome containing as a membrane component one or more selected from the group consisting of a surfactant and a cholesterol ester. It is a liposome skin absorption control release agent for controlling the site of liposome absorption by changing the amount in the range of 0 to 100% by mass.

  In the release agent, when at least one selected from the group consisting of a surfactant and a cholesterol ester is used in combination with a phospholipid as a membrane constituent of the liposome, the control of the site of liposome absorption through the skin becomes more accurate. .

  The surfactant in the release agent is preferably an acylmethyl taurate salt and / or a polyoxyethylene hydrogenated castor oil.

  The acylmethyl taurine salt in the release agent is preferably a methyl stearoyl taurine salt.

  The phospholipid in the release agent is preferably a hydrogenated phospholipid.

  Furthermore, the present invention is a skin external preparation containing the liposome skin absorption control release agent.

  According to the present invention, by changing the content of phosphatidylcholine in the phospholipid of the liposome containing phospholipid as a membrane constituent component in the range of 0 to 100% by mass, the site of liposome absorption through skin can be controlled. it can. In particular, it is possible to control the absorption ratio of the receptor in the skin and the deep skin composed of the dermis. Further, the liposome used in the above method is useful as a skin absorption control release agent for liposomes for controlling the site of liposome absorption of the skin, particularly for controlling the absorption ratio of the skin receptors and dermis to the deep skin. It is. The liposome skin absorption control release agent is contained in an external preparation for skin and exhibits its effect.

  Hereinafter, the best mode for carrying out the present invention will be described in detail.

  In the present invention, phospholipid is used as a constituent of the liposome membrane. The phospholipid contains 0 to 100% by mass of phosphatidylcholine (lecithin), and other components include phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, sphingomyelin and the like. Therefore, for example, a phospholipid containing 0% by mass of phosphatidylcholine is a phospholipid made of phosphatidylethanolamine or the like other than phosphatidylcholine, and a phospholipid containing 100% by mass of phosphatidylcholine is a phospholipid made of phosphatidylcholine. The phospholipid in the present invention is not particularly limited as long as it is used for cosmetics, quasi drugs, pharmaceuticals and the like. In the present invention, phospholipid is a concept including natural phospholipids, phospholipid derivatives such as hydrogenated phospholipids, synthetic phospholipids, and the like. For the phosphatidylcholine, natural soybean lecithin, egg yolk lecithin and the like can be used.

  A commercially available product can be used as the phospholipid containing 0 to 100% by mass of the phosphatidylcholine. Examples of commercially available products include lucinol S-10EX (phosphatidylcholine content 90% by mass) and lucinol S-10E. (Phosphatidylcholine content 50% by mass), lucinol S-PIE (phosphatidylcholine content 20% by mass) (manufactured by Nikko Chemicals Co., Ltd.) and the like.

  The content of the phospholipid according to the present invention is preferably 0.5 to 10.0% by mass in the liposome. In this range, sufficient effects of the present invention can be obtained.

  In the present invention, the content of phosphatidylcholine in the phospholipid used as the membrane constituent of the liposome is adjusted in the range of 0 to 100% by mass. When liposomes containing phospholipids as membrane constituents are percutaneously absorbed into the skin, as will be demonstrated later by the content of the phosphatidylcholine, the absorption site in the range from the skin surface of the skin to the receptor should be different. Can do. As the phosphatidylcholine content in the phospholipid is increased, the liposomes are absorbed more in the direction of the skin deeper and the content of the phosphatidylcholine in the phospholipid is higher, the skin deep part consisting of the receptor and the dermis (hereinafter simply referred to as the skin deep part). ) Selectively absorbed. Conversely, as the content of phosphatidylcholine in the phospholipid is decreased, the absorption in the deep skin direction is suppressed, the absorption in the deep skin is less, the absorption in the skin surface direction is increased, and the epidermis and selectively It is absorbed by the surface portion on the surface side. Therefore, the control method which can control the skin absorption arrival site | part of a liposome is provided by changing content of the phosphatidylcholine in a phospholipid in 0-100 mass%. Moreover, the liposome which changed content of the phosphatidylcholine in such a phospholipid in the range of 0-100 mass% is useful as a skin absorption control release agent of a liposome for controlling the skin absorption arrival site | part of a liposome.

  In the present invention, one or more selected from the group consisting of a surfactant and a cholesterol ester can be used in combination with the phospholipid as a constituent of the liposome membrane. By using in combination with these, the control of the liposome absorption site of the liposome can be made more accurate.

  The surfactant used in combination with the phospholipid is not particularly limited, but a nonionic surfactant and an anionic surfactant are preferable.

  Examples of nonionic surfactants include sorbitan fatty acid esters (such as sorbitan monostearate and sorbitan sesquioleate), glycerin fatty acids (such as glyceryl monostearate), and propylene glycol fatty acid esters (such as propylene glycol monostearate). ), Hydrogenated castor oil derivative, glycerin alkyl ether, polyoxyethylene (hereinafter referred to as POE) sorbitan fatty acid esters (POE sorbitan monooleate, POE sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE sorbite monolaur) Rate), POE glycerin fatty acid esters (POE glycerin monoisostearate, etc.), polyethylene glycol (hereinafter referred to as PEG) fatty acid esters (PEG monoolee) , PEG distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / polyoxypropylene (hereinafter referred to as POP) alkyl. Examples include ethers (POE / POP2-decyltetradecyl ether, etc.), POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), sucrose fatty acid esters, alkyl glucosides and the like. One kind or two or more kinds of nonionic surfactants are arbitrarily selected and used.

  Of these, a POE hydrogenated castor oil derivative is preferably used in the present invention. Among these, a POE hydrogenated castor oil derivative having an average added mole number of POE of 40 to 80 is preferable. In particular, POE hydrogenated castor oil (hereinafter referred to as HCO, for example, when the average added mole number of POE is 60 is indicated as HCO-60) having an average added mole number of POE of 40 to 80 is preferable.

  Examples of anionic surfactants include, for example, fatty acid soap (eg, sodium laurate, sodium palmitate, etc.), alkyl sulfate (eg, potassium lauryl sulfate), alkyl sulfate triethanolamine ether, acylmethyl Taurine salts (for example, methyl stearoyl taurine salt, methyl oleoyl taurine salt, methyl stearoyl taurine sodium (hereinafter referred to as SMT), methyl oleoyl taurine sodium, etc.) are preferably used. Of these, acylmethyl taurine salts represented by SMT are particularly preferred.

  In the present invention, the cholesterol ester used in combination with the phospholipid is an ester of cholesterol and a higher fatty acid. The higher fatty acid is preferably a linear or branched saturated or unsaturated fatty acid having 12 to 24 carbon atoms, such as myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid. Linolenic acid, arachidonic acid, macadamia nut oil fatty acid. Of these, stearic acid, oleic acid, and palmitic acid are particularly preferable. Specific examples of cholesterol esters include cholesteryl laurate, cholesteryl myristate, cholesteryl palmitate, cholesteryl oleate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl linoleate, macadamia nut oil fatty acid cholesteryl, lauroyl glutamate di ( Cholesteryl / octyldodecyl) and the like.

  The content of one or more selected from the group consisting of a surfactant and a cholesterol ester is not particularly limited, but is preferably 5 to 80% by mass with respect to the phospholipid in the liposome. In this range, sufficient effects of the present invention can be obtained.

  As a constituent component of the liposome membrane, other known components may be further added within a range not impairing the effects of the present invention. Liposomes can encapsulate various lipophilic or hydrophilic components in the phospholipid membrane and the inner aqueous phase, respectively. For example, the lipophilic components that can be encapsulated in the phospholipid membrane include avocado oil, almond oil, olive oil, sesame oil, sasanqua oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil Vegetable oils such as cottonseed oil, peanut oil, jojoba oil, or vegetable waxes, isopropyl myristate, isopropyl palmitate, hexyl laurate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl 2-ethylhexanoate, Ester oils such as glyceryl tri-2-ethylhexanoate and trimethylolpropane trioctanoate, hydrophobic amino acids such as phenylalanine, tryptophan, isoleucine, leucine, proline, methionine, valine, alanine, and lipophilic derivatives thereof, retinol, retina Vitamin A such as le, retinoic acid and their lipophilic derivatives, provitamin A such as α-carotene, β-carotene and γ-carotene, vitamin D such as cholecalciferol and ergocalciferol and their parents Provitamin Ds such as oil derivatives, 7-dehydrocholesterol and ergosterol and lipophilic derivatives thereof, vitamin Es such as α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol and lipophilic derivatives thereof, phylloquinone , Menaquinone, menadione, etc., lipophilic vitamins such as vitamin K and their lipophilic derivatives, ubiquinone and its lipophilic derivatives, lipoic acid and its lipophilic derivatives, linoleic acid and its lipophilic derivatives, linolenic acid and its parent Oil derivatives, arachidonic acid and its lipophilic derivatives, etc. Lipophilic vitamin-like agents such as riboflavin butyrate, pyridoxine dicaprylate, pyridoxine dipalmitate, ascorbyl palmitate, ascorbyl dipalmitate, lipophilic derivatives of water-soluble vitamins, guaiazulene, ethyl guaiazulenesulfonate, glycyrrhetinic acid And lipophilic anti-inflammatory agents such as stearyl. These components can be used alone or in combination of two or more.

Moreover, as the hydrophilic component to be encapsulated in the inner aqueous phase, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol and glycerin, monosaccharides and oligosaccharides such as glucose, galactose, fructose, saccharose and maltose, Sugar alcohols such as inositol, sorbitol, maltitol, hydrophilic amino acids such as lysine, glutamine, asparagine, glutamic acid, aspartic acid, threonine, arginine, serine, pyrrolidone carboxylic acid and salts thereof, hydrophilic derivatives, vitamins such as thiamine B ₁ class and salts and hydrophilic derivatives thereof, riboflavin as vitamin B ₂ compounds and salts and hydrophilic derivatives thereof, nicotinic acid, nicotinic acid amide niacin acids and as well as hydrophilic derivatives of these salts, pyridoxine, pyrido Searle, vitamin B ₆ acids and salts thereof and hydrophilic derivatives thereof such as pyridoxamine, pantothenic acid and its salts and hydrophilic derivatives, biotin and its salts and hydrophilic derivatives, folic acid and its salts and hydrophilic derivatives, cobalamin as vitamin B ₁₂ And their salts and hydrophilic derivatives, hydrophilic vitamins such as ascorbic acid and its salts and hydrophilic derivatives, orotic acid and its salts and hydrophilic derivatives, carnitine and its salts and hydrophilic derivatives, hesperidin, erodidictin, rutin Hydrophilic vitamin-like agents such as vitamin Ps such as 2-hydroxycarboxylic acids such as glycolic acid, lactic acid, citric acid and their salts and hydrophilic derivatives, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, etc. Saccharides and their salts and hydrophilic derivatives Peptides such as soluble collagen, collagen hydrolyzate, elastin hydrolyzate, keratin hydrolyzate and their salts, and hydrophilic modification products, allantoin and its salts and hydrophilic derivatives, guaiazulene sulfonate, glycyrrhizic acid and its salts In addition, hydrophilic anti-inflammatory agents such as hydrophilic derivatives, extracts from plant polar solvents, and the like can be mentioned. These components are used alone or in combination of two or more.

  The liposome according to the present invention can be prepared using a known method without particular limitation. For example, the membrane component is dissolved or dispersed in water together with other active components such as polyhydric alcohol, if necessary, and the inclusion component in the liposome. In the dispersion, it is preferable to increase the dispersion by, for example, heating (for example, 80 to 90 ° C.), high-speed stirring (for example, a stirring speed of 3000 rpm or more with a homomixer) and the like. Next, this aqueous dispersion is finely dispersed using a high-pressure mixer (for example, a microfluidizer, an APV homogenizer, etc.) to form liposomes, and an aqueous liposome dispersion is obtained.

  Liposomes encapsulating an oily core containing an oil-soluble physiologically active substance are prepared by, for example, dissolving an oil-soluble physiologically active substance in an oily component and adding a liposome membrane component such as phospholipid to this and stirring. Then, it can prepare as an aqueous dispersion by adding water and stirring well. For stirring, ultrasonic waves may be used as necessary.

  Further, the membrane component and the aqueous solution are stirred at a temperature higher than the phase transition temperature of the membrane component, or the membrane component is glycerin, diglycerin, propylene glycol, dipropylene glycol, polyethylene glycol, 1,3- Mixed with water-soluble non-volatile organic solvent such as polyhydric alcohols such as butylene glycol, diethylene glycol monoethyl ether, sorbitol, maltitol, glyceryl esters such as glyceryl monoacetate, glyceryl diacetate, glycerophosphate, It can also be prepared by dispersing in an aqueous solution. Further, ultrasonic treatment may be added to the obtained liposome suspension.

  Other methods for producing liposomes include a thin film method, reverse layer evaporation method, ethanol injection method, dehydration-rehydration method and the like.

  The liposome skin absorption control release agent according to the present invention has a wide range of applications and can be applied in various fields. For example, cosmetics including quasi-drugs, pharmaceuticals and the like can be mentioned.

  The liposome skin absorption control release agent according to the present invention is blended in a skin external preparation and exhibits an excellent effect. Liposomes are generally present as aqueous dispersions and are optionally diluted in water. In the skin external preparation, it is optionally diluted with water in the skin external preparation. The liposome in the present invention is a concept including an optionally diluted liposome aqueous dispersion present in the skin external preparation.

  In the external preparation for skin according to the present invention, components usually used in external preparations for skin such as cosmetics and pharmaceuticals including quasi-drugs, such as oils, surfactants, powders, coloring materials, water, alcohols, thickeners, Chelating agents, silicones, antioxidants, ultraviolet absorbers, humectants, fragrances, various medicinal ingredients, preservatives, pH adjusters, neutralizing agents, and the like are appropriately blended as necessary.

  Examples of the external preparation for skin according to the present invention include pharmaceuticals (ointment etc.), quasi-drugs (ointment etc.) and cosmetics [milky lotion, cream, gel, essence (beauty liquid), hair cosmetics, body cosmetics, etc.]. Widely applicable to form.

  Hereinafter, the present invention will be specifically described with reference to examples. Prior to the description of the examples, the effect test method used in the present invention will be described.

1. Transdermal absorbability (1) Test method and evaluation Pork skin coated with a sample added with fluorescent substance 4MUS (4-Methylumbelliferyl sulfate potassium salt) is set in a Franz diffusion cell and left at 32 ° C for 24 hours. 4MUS contained therein was decomposed with Sulfatase (Type IV from Limpets) and then quantified by fluorescence detection to measure the amount of absorption of the fluorescent substance. The measured skin sites were the receptor, dermis, and epidermis, and the fluorescent substances present on the tape affixed to the skin were measured and taken as the outermost absorption in the epidermis.

  Next, production examples of liposomes will be given. Using the components listed in Table 1 and Table 2, liposomes were produced by the following method. In Tables 1 and 2, the ratio of each component used is shown in mass% (total amount of compounding is 100 mass%).

(Production method)
(1) All the blended components were weighed, and components other than purified water were added to the purified water with stirring at room temperature and dispersed.
(2) Thereafter, the mixture was heated to 80 to 90 ° C. and stirred at high speed with a homomixer to enhance dispersion.
(3) Next, the dispersion liquid of the above item (2) was finely dispersed using a high-pressure mixer (microfluidizer) to form liposomes.
(4) Next, this dispersion was cooled to room temperature to obtain a liposome dispersion.

In Table 1,
(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)
(Note 2) Lucinol S-10E (phosphatidylcholine content 50% by mass) (manufactured by Nikko Chemicals)
(Note 3) Lucinol S-PIE (Phosphatidylcholine content 20% by mass) (manufactured by Nikko Chemicals)

In Table 2,
(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)
(Note 2) Lucinol S-10E (phosphatidylcholine content 50% by mass) (manufactured by Nikko Chemicals)
(Note 3) Lucinol S-PIE (Phosphatidylcholine content 20% by mass) (manufactured by Nikko Chemicals)

  An effect test was performed on the liposomes of Examples 1 to 13, and the amount of fluorescent substance absorbed at each skin site was measured. As test samples, liposomes produced by adding a fluorescent substance 4MUS to the liposome components of Examples 1 to 13 listed in Tables 1 and 2 were used. The evaluation results are shown in Tables 3 and 4. In the table, the ratio (%) of the total skin absorption amount to the application amount and the absorption amount of each part (% in the total skin absorption amount) were shown.

  As can be seen from Table 3 and Table 4, the liposome (Example 1) having a phospholipid (lucinol S-10EX) containing 90% by mass of phosphatidylcholine as a membrane component has a large amount of absorption to the receptor in the skin, Over 90% of the total absorbed amount is absorbed in the deep part of the skin consisting of the receptor and the dermis. From this, it can be seen that liposomes having phosphatidylcholine-rich phospholipid as a membrane component are selectively absorbed in the deep part of the skin.

  In addition, a liposome (Example 2) containing a phospholipid (lucinol S-10E) having a low phosphatidylcholine content (lucinol S-10E content of 50% by mass) as compared with lucinol S-10EX is a receptor in the skin. The amount of absorption into the dermis is smaller than that of the liposome of Example 1, and the receptor in the skin and the absorption reaching the deep part of the skin consisting of the receptor and the dermis are suppressed, and the absorption to the shallower part is selectively performed. I understand that

  Furthermore, a liposome (Example 3) comprising a phospholipid (lucinol S-PIE) having a lower phosphatidylcholine content as compared to lucinol S-10E (phosphatidylcholine content 20 mass%) as a membrane constituent is a receptor in the skin. And the absorption amount to the skin deep part which consists of dermis is still smaller compared with the liposome of Example 2, On the other hand, the absorption amount to an epidermis and a tape part becomes large compared with the liposome of the said Examples 1-2. Thus, it can be seen that the absorption to a shallow site in the skin, particularly the epidermis and the tape part, is selectively performed.

  Since the absorption amount of the liposome of Example 2 into the epidermis and the tape part is smaller than that of the liposome of Example 3, the liposome of Example 2 is selectively absorbed into the intermediate deep part in the skin. It can be seen that

  In Examples 4 to 13, the ratio (%) of the total skin absorption amount to the coating amount when phospholipid and one or more selected from the group consisting of surfactant and cholesterol ester are used in combination as a constituent of the liposome membrane In addition, the absorption amount of each part (% of the total skin absorption amount) is shown.

  According to these, the tendency similar to Examples 1-3 is seen. That is, a liposome containing 90% by mass of phosphatidylcholine (Lucinol S-10EX) and cholesteryl stearate, cholesteryl oleate, HCO-60 and SMT as membrane components (Examples 4 to 6 and 11) ) Has a large amount of absorption to the receptor in the skin, and more than 90% of the total absorption is absorbed in the deep skin composed of the receptor and the dermis.

  In addition, compared with Example 1, the liposomes of Examples 4 to 6 and 11 are more effective in the skin than the liposomes to which any of cholesteryl stearate, cholesteryl oleate, HCO-60 and SMT is not added as a membrane component. It can be seen that the absorption amount of the receptor to the receptor and the selective reaching absorption to the deep part of the skin composed of the receptor and the dermis (the amount exceeding 90% of the total absorption amount is absorbed) are clearer. Therefore, it can be seen that when one or more selected from the group consisting of surfactants and cholesterol esters are used in combination with phospholipids as membrane constituents of liposomes, the control of liposome skin absorption reaching sites becomes more accurate. .

  In addition, a phospholipid (lucinol S-10E) having a lower phosphatidylcholine content than lucinol S-10EX (phosphatidylcholine content 50% by mass) and any one of HCO-60, cholesteryl stearate and sodium methyloleoyl taurine Liposomes (Examples 7, 8 and 12) as membrane constituents have an absorption amount to the receptor in the skin and an absorption amount to the deep skin composed of the receptor and dermis as compared with the liposomes of Examples 4 to 6 and 11. It can be seen that the absorption in the skin deeply consisting of the receptor in the skin and the receptor and the dermis is suppressed, and absorption at a shallower site is selectively performed. In addition, it is the same as that of Example 2 that the liposomes of Examples 7, 8 and 12 are selectively absorbed into the intermediate deep part in the skin.

  Furthermore, from the comparison with Example 2, the liposomes of Examples 7, 8 and 12 were more effective in accepting the receptor and the liposomes compared with liposomes to which any one of HCO-60, cholesteryl stearate and sodium methyloleoyl taurine was not added as a membrane constituent. It can be seen that the selective absorption into a site shallower than the deep part of the dermis (an intermediate deep part in the skin) becomes clearer. From now on, when one or more selected from the group consisting of a surfactant and a cholesterol ester are used in combination with phospholipids as membrane constituents of liposomes, it is possible that the control of the site of liposome absorption through the skin becomes more accurate. I understand.

  Furthermore, the phosphatidylcholine content is less than lucinol S-10E (phosphatidylcholine content 20% by mass), and any one of cholesteryl stearate, SMT, and HCO-80 is used as a membrane component. The liposomes (Examples 9, 10 and 13) absorb less to the receptor in the skin and to the skin deep part consisting of the receptor and the dermis than the liposomes of Examples 7, 8 and 12, and the skin It can be seen that absorption to the deep part of the skin composed of the inner receptor and the receptor and the dermis is further suppressed, and absorption to a shallower site is performed. In particular, the liposomes of Examples 9, 10 and 13 have a clearly higher absorption amount to the epidermis and the tape part than the liposomes of Examples 4 to 8 and 11 to 12, and the epidermis and tape in the skin. It can be seen that absorption into a shallow region called a region is selectively performed.

  In addition, compared with Example 3, compared with liposomes to which any one of cholesteryl stearate, SMT, and HCO-80 is not added as a membrane constituent, selective absorption to the shallow part of the skin consisting of the epidermis and the tape part is more. You can see that it is clear. From now on, when one or more selected from the group consisting of a surfactant and a cholesterol ester are used in combination with phospholipids as membrane constituents of liposomes, it is possible that the control of the site of liposome absorption through the skin becomes more accurate. I understand.

  From the above, it is clear that the absorption rate to the receptor and the dermis is higher, the higher the phosphatidylcholine content in the phospholipid, the higher the absorption rate. Is transferred to a shallow part of the skin, and it can be seen that the site of liposome absorption through the skin can be controlled by the content of phosphatidylcholine in the phospholipid. Therefore, it is useful as a method for controlling the site of skin absorption of the liposome by changing the content of the phosphatidylcholine in the range of 0 to 100% by mass, and as a skin absorption control release agent for the liposome used in the method. It is clear.

  The formulation example of the external preparation for skin based on this invention is shown below. All the external preparations for skin had an excellent effect as a liposome skin absorption control release agent. In addition, manufacture was manufactured according to the manufacturing method of the liposome of the said Examples 1-13.

[Formulation example 1] Toner lotion component Amount (% by mass)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
HCO-60 1.0
Phospholipid (Note 1) 4.0
Ethanol 10.0
Purified water residue

(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)

[Formulation Example 2] lotion component blending amount (% by mass)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
SMT 1.0
Phospholipid (Note 2) 4.0
Ethanol 10.0
Purified water residue

(Note 2) Lucinol S-10E (phosphatidylcholine content 50% by mass) (manufactured by Nikko Chemicals)

[Formulation example 3] lotion component blending amount (% by mass)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
HCO-60 1.0
Phospholipid (Note 3) 4.0
Ethanol 10.0
Purified water residue

(Note 3) Lucinol S-PIE (Phosphatidylcholine content 20% by mass) (manufactured by Nikko Chemicals)

[Formulation Example 4] lotion component blending amount (% by mass)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
HCO-80 1.5
POE (20) sorbitan monolaurate 0.5
Phospholipid (Note 1) 7.0
Ethanol 10.0
Purified water residue

(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)

[Formulation Example 5] lotion component content (mass%)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
Methyl oleoyl taurine sodium 0.5
Phospholipid (Note 1) 5.0
Ethanol 10.0
Purified water residue

(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)

[Formulation Example 6] lotion component content (mass%)
Glycerin 8.0
1,3-butylene glycol 3.0
Oleyl alcohol 0.1
Cholesteryl palmitate 1.5
Phospholipid (Note 1) 3.0
Ethanol 10.0
Purified water residue

(Note 1) Lucinol S-10EX (phosphatidylcholine content 90% by mass) (manufactured by Nikko Chemicals)

Claims (11)

  When the liposome containing phospholipid containing 0 to 100% by mass of phosphatidylcholine as a membrane component is absorbed into the skin, the content of phosphatidylcholine in the phospholipid is changed within the range of 0 to 100% by mass. A method of controlling the skin absorption site.   The content of phosphatidylcholine in the phospholipid when the skin contains a phospholipid containing 0 to 100% by mass of phosphatidylcholine and a liposome containing one or more selected from the group consisting of a surfactant and a cholesterol ester as a membrane component A method for controlling the site of the liposomes to reach skin absorption by changing the pH in the range of 0 to 100% by mass.   The method according to claim 2, wherein the surfactant is an acylmethyl taurine salt and / or a polyoxyethylene hydrogenated castor oil.   The method according to claim 3, wherein the acylmethyl taurine salt is a methyl stearoyl taurine salt.   The method according to any one of claims 1 to 4, wherein the phospholipid is a hydrogenated phospholipid.   A liposome containing a phospholipid containing 0 to 100% by mass of phosphatidylcholine as a membrane component, and the phosphatidylcholine content in the phospholipid is changed in a range of 0 to 100% by mass to control the site of liposome absorption by skin. Liposomes skin absorption control release agent.   The phosphatidylcholine content in the phospholipid is 0-100 mass, comprising phospholipids containing 0-100 mass% of phosphatidylcholine and liposomes containing one or more selected from the group consisting of surfactants and cholesterol esters as membrane constituents. A lipodermal skin absorption control release agent for controlling the site of liposome skin absorption by changing in the range of%.   The liposome skin absorption control release agent according to claim 7, wherein the surfactant is an acylmethyl taurine salt and / or polyoxyethylene hydrogenated castor oil.   9. The liposome skin absorption control release agent according to claim 8, wherein the acylmethyl taurine salt is methyl stearoyl taurine salt.   10. The liposome skin absorption control release agent according to any one of claims 6 to 9, wherein the phospholipid is a hydrogenated phospholipid.   The skin external preparation containing the skin absorption control release agent of the liposome as described in any one of Claims 6 thru | or 10.