JP2015017053A - Vesicle dispersion composition, method for producing of vesicle dispersion composition, and external preparation for skin comprising vesicle dispersion composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vesicle dispersion composition in which a vesicle including an active ingredient comprising phospholipid and ceramide as a constitutional component is improved by increasing the persistence of a moisturizing effect derived from ceramide at an application site, and increasing the percutaneous absorption sustainability of the active ingredient included by the vesicle.SOLUTION: The above subject is solved by a vesicle dispersion composition containing a vesicle containing phospholipid and ceramide at least as a constitutional component, and polymer containing a constitutional unit induced from a specific monomer as an essential constitutional unit.

Description

  The present invention relates to a preparation technique useful for an external preparation for skin, and more particularly to a preparation technique using a vesicle dispersion composition.

  The skin has a function of preventing invasion of foreign substances that adversely affect the living body such as bacteria, viruses, chemical substances, etc., which are undesirable in the living body. In particular, the part that plays a central role in the function is the stratum corneum having a dense multi-layer structure of stratum corneum cells. On the other hand, in order to improve skin spots, wrinkles, and dryness, it is very important that chemicals such as whitening ingredients, anti-wrinkle ingredients, anti-inflammatory ingredients, and moisturizing ingredients extracted from plants reach the inside of the skin. However, since the percutaneous absorption of these components is suppressed by the function of preventing the invasion of foreign substances into the stratum corneum, technological development relating to formulations and techniques for promoting percutaneous absorption has been actively conducted in the past.

  For example, a method using a card house or network structure constructed by an oily gel (Patent Document 1), a method using ultrasonic waves as a driving force for percutaneous absorption (Patent Document 2), N-methyl-2-pyrrolidone, etc. A method using a solvent (Patent Document 3), a method using a transdermal absorption promoting component such as lauroyl sarcosine (Patent Document 4), a liposome having an inner aqueous phase inside a sphere having a phospholipid bilayer structure, Examples thereof include a method of encapsulating a drug in the internal aqueous phase of niosome and blending it into a skin external preparation (Patent Document 5). Although these techniques could improve the reach of the plant extract to the dermis, it was difficult to say that the reach was sufficient.

  In addition, as a preparation technique using vesicles, techniques for stably adding a poorly soluble component such as ceramide or phytosterol to an external preparation for skin are known (Patent Documents 6 and 7). Furthermore, a technique is also known in which a component having reactivity with water is encapsulated and stably contained in an aqueous preparation (Patent Document 8).

  On the other hand, when the percutaneous absorption of an active ingredient is improved with a percutaneous absorption enhancer or the like, there has been a problem that the barrier function of the skin is impaired. However, to solve this problem, by using a so-called “pseudo-biological polymer” having a biological component constituting the living body or a similar structure in the side chain, the active ingredient is applied to the skin without impairing the barrier function. It is solved by using a technique to act (Patent Document 9).

  Furthermore, as a technique for improving the sustainability of percutaneous absorption by sustained release, a technique using biocompatible hyaluronic acid-carrying nanoparticles is known, and the effect of penetration of hyaluronic acid into the skin is known. Cosmetics having a high moisturizing effect and having a sustained release effect have been developed (Patent Document 10).

JP 2000-103722 A JP 11-335271 A JP-A-10-265379 Japanese Patent Application Laid-Open No. 09-169637 JP 2004-143080 A JP 2006-199635 A Japanese Patent No. 3555777 JP 09-040543 A JP 2003-160462 A JP 2010-150151 A

  The present invention has been made under such circumstances, and is a new vesicle that enhances the persistence of the ceramide-derived moisturizing effect at the application site and enhances the percutaneous absorption persistence of the active ingredient contained in the vesicle. It is an object to provide a dispersion composition.

  In order to solve the above-mentioned problems, the present inventors have studied the constituents of vesicles and the dispersed phase, and as a result, have found that a new vesicle dispersion composition as shown below can solve the above problems. Was completed. That is, the present invention is as follows.

<1> A vesicle dispersion composition comprising a vesicle containing at least the following components A and B as components and a component C:
A) a phospholipid B) ceramide C) a polymer containing a structural unit derived from the monomer represented by the general formula (1) as an essential structural unit, and a structural unit derived from the monomer represented by the general formula (2) One or two or more polymers selected from the group consisting of polymers containing as essential constituent units

（一般式（１）中、Ｒ¹は水素原子またはメチル基を、Ｒ²はアミノ酸残基、ポリアミン残基又はアミノアルコール残基を表す。Ｘは酸素原子又はＮＨで表される基を表す。）

(In the general formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents an amino acid residue, a polyamine residue or an amino alcohol residue. X represents an oxygen atom or a group represented by NH. )

（一般式（２）中、Ｒ³は水素原子またはメチル基を表す。）

(In general formula (2), R ³ represents a hydrogen atom or a methyl group.)

<2> The vesicle dispersion composition according to <1>, wherein the phospholipid is lecithin.
<3> The vesicle dispersion composition according to <1> or <2>, further comprising a plant extract.
<4> A method for producing a vesicle dispersion composition according to any one of <1> to <3>,
(I) a step of dispersing the component C in an aqueous phase to obtain a dispersion; and
(Ii) a step of dispersing a vesicle containing at least the components A and B prepared in advance as constituents in the obtained dispersion to obtain a vesicle dispersion composition;
Manufacturing method.
<5> A skin external preparation containing the vesicle dispersion composition according to any one of <1> to <3> or the vesicle dispersion composition produced by the production method according to <4>.

  According to the present invention, vesicles containing an active ingredient containing phospholipids and ceramide as constituent components are dispersed in an aqueous phase containing a specific polymer, thereby enhancing the persistence of the ceramide-derived moisturizing effect at the application site. In addition, a vesicle dispersion composition in which the percutaneous absorption persistence of an active ingredient contained in the vesicle can be provided.

The vesicle dispersion composition according to this embodiment is characterized by containing a vesicle containing at least the following components A and B as components and component C.
A) phospholipids,
B) Ceramide,
C) A polymer containing a structural unit derived from the monomer represented by the general formula (1) as an essential structural unit and a structural unit derived from the monomer represented by the general formula (2) as an essential structural unit One or more polymers selected from the group consisting of polymers

（一般式（１）中、Ｒ¹は水素原子またはメチル基を、Ｒ²はアミノ酸残基、ポリアミン残基又はアミノアルコール残基を表す。Ｘは酸素原子又はＮＨで表される基を表す。）

(In the general formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents an amino acid residue, a polyamine residue or an amino alcohol residue. X represents an oxygen atom or a group represented by NH. )

（一般式（２）中、Ｒ³は水素原子またはメチル基を表す。）

(In general formula (2), R ³ represents a hydrogen atom or a methyl group.)

<1-1. Phospholipid>
The vesicle dispersion composition according to this embodiment contains phospholipid as an essential component. Phospholipid is used as a vesicle constituent component, stabilizes the vesicle structure, contributes to storage stability, and a vesicle composition containing the vesicle composition is excellent in skin penetration and moisturizing feeling.
Examples of the phospholipid include glycerophospholipid and sphingophospholipid.
Glycerophospholipid is a substance having a glycerophosphoric acid skeleton, and has a fatty acid ester, a long-chain alkyl ether, a vinyl ether or the like as a lipophilic group. Specifically, phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphadiylinositol, phosphatidylinositol polyphosphate, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidyl Examples include serine, lysophosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidic acid.
Sphingophospholipids have long-chain bases or long-chain fatty acids such as sphingosine and phytosphingosine, and phosphoric acid or phosphonic acid. Ceramide 1-phosphate derivatives (such as sphingomyelin), ceramide 1-phosphonic acid derivatives ( Ceramide aminoethylphosphonic acid and the like).

The phospholipid used in this embodiment may be a natural product extracted and purified from animals or plants, or may be chemically synthesized, and may be subjected to processing such as hydrogenation or hydroxylation. As a natural product, lecithin, which is an extract / purified product from soybean or egg yolk, is preferable because it is easy to obtain a commercial product.
The phospholipid content in the vesicle dispersion composition is usually 0.001 to 10% by mass, preferably 0.01 to 5.0% by mass, more preferably 0.01 to 1.0% by mass. is there. Within this range, the vesicle structure containing ceramide is stabilized, and the storage stability is improved.

<1-2. Ceramide>
The vesicle dispersion composition according to this embodiment contains ceramide as an essential component. By containing ceramide in the vesicle, the moisturizing effect is remarkably improved.
As the ceramide, any of ceramide type 1 to ceramide type 7 can be used. However, ceramide type 2 and ceramide type 3 are commercially available, and it is preferable to use such commercially available products. As a commercially available product of ceramide type 2, “ceramide TIC-001” (manufactured by Takasago Inc.), and as ceramide type 3, “ceramide III” (manufactured by Cosmo Farm) can be preferably exemplified. Other commercially available products of ceramide include, for example, “Ceramide I” (ceramide 1) manufactured by Cosmo Farm,
“Ceramide IIIB” (ceramide 3), “Ceramide VI” (ceramide 6) and the like can be preferably exemplified. These may contain a single species or in combination of two or more species.
The content of ceramide in the vesicle dispersion composition is usually 0.0001 to 10% by mass, preferably 0.001 to 5.0% by mass, more preferably 0.01 to 1.0% by mass. . The mass ratio of phospholipid to ceramide is usually 30:70 to 90:10, preferably 40:60 to 90:10, and more preferably 65:35 to 80:20. Within this range, the vesicle structure is stabilized, storage stability is improved, and a sufficient moisturizing effect is obtained.

<1-3. Polymer>
The vesicle dispersion composition according to this embodiment includes, as an essential component, a polymer containing a structural unit derived from a monomer represented by the general formula (1) as an essential structural unit and a monomer represented by the general formula (2) 1 type, or 2 or more types of polymers selected from the group which consists of a polymer which contains the structural unit derived from as an essential structural unit is contained.

（一般式（１）中、Ｒ¹は水素原子またはメチル基を、Ｒ²はアミノ酸残基、ポリアミン残基又はアミノアルコール残基を表す。Ｘは酸素原子又はＮＨで表される基を表す。）

(In the general formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents an amino acid residue, a polyamine residue or an amino alcohol residue. X represents an oxygen atom or a group represented by NH. )

（一般式（２）中、Ｒ³は水素原子またはメチル基を表す。）

(In general formula (2), R ³ represents a hydrogen atom or a methyl group.)

By containing the polymer, the vesicle dispersion composition according to this embodiment enhances the persistence of the ceramide-derived moisturizing effect at the application site and also enhances the percutaneous absorption persistence of the active ingredient contained in the vesicle. it can. This is because the polymer is present outside the vesicle comprising phospholipids and ceramide as a constituent component, so that the polymer serves to coat the vesicle from above at the application site, and the application site and the vesicle are sufficiently in contact with each other. It is because it can be made.
Further, since the polymer is present outside the vesicle comprising phospholipid and ceramide as constituent components, the repulsion due to the charge of the polymer prevents the vesicles from being united with each other. Dispersion stability is improved. Then, as a result of the improvement of the stability, it is possible to sufficiently and continuously absorb the ceramide having a moisturizing effect and the active ingredient in the vesicle.

<1-3-1. Polymer containing structural unit derived from monomer represented by general formula (1) as essential structural unit>
R ² in the polymer containing a structural unit derived from the monomer represented by the general formula (1) used in this embodiment as an essential structural unit is an amino acid residue, a polyamine residue or an amino alcohol residue; An amino acid residue is preferred.
The amino acid residue is not particularly limited as long as it is a commonly known amino acid, and examples thereof include glycine residue, alanine residue, glutamine residue, lysine residue, arginine residue, etc., preferably lysine residue. It is a group.
The polyamine residue is not particularly limited as long as it is an amine having two or more amino groups that may be substituted with alkyl groups in the same molecule, and diamine, triamine, tetraamine, or these amino groups are alkyl groups. And the like. Among these, diamine or a compound in which the amino group is substituted with an alkyl group is preferable, and among diamines, ethylenediamine, 1,4-diamino-n-butane, 1,6-diamino- n-hexane and the like.
The amino alcohol residue is not particularly limited as long as it is an organic compound having an amino group which may be substituted with an alkyl group in the same molecule and an alcoholic hydroxyl group. An ethanolamine residue and a trimethylaminoethanol residue are preferable.
In addition, since R ¹ is a hydrogen atom or a methyl group, the essential constituent unit of the polymer is
Contains a (meth) acryloyl group. X is a group represented by an oxygen atom or NH, and X is determined by whether R ² is an amino acid residue, a polyamine residue or an amino alcohol residue.
Examples of the polymer containing a structural unit derived from the monomer represented by the general formula (1) as an essential structural unit include poly (meth) acryloyl lysine, among which polymethacryloyl lysine is preferable.

The polymer containing the structural unit derived from the monomer represented by the general formula (1) as an essential structural unit may be a homopolymer obtained by polymerizing only the monomer as the essential structural unit.
Such homopolymers are already commercially available, and examples thereof include PM lysine (polymethacryloyl lysine (molecular weight 50,000 to 200,000); manufactured by Gifu Shellac Co., Ltd.).

  In addition, a polymer containing a structural unit derived from the monomer represented by the general formula (1) as an essential structural unit may share any other monomer as a structural unit as long as the effect of the essential structural unit is not hindered. It may be a polymerized copolymer. In that case, the content of the essential constituent unit in the copolymer is usually 50% by mass or more, and preferably 60% by mass or more. In addition, in a vesicle dispersion composition, a seed | species can also be contained among the said homopolymer and the said copolymer, and it can also contain in combination of 2 or more type.

  Examples of the optional monomer include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, octyl (meth) acrylate, and lauryl (meth) acrylate. , Alkyl (meth) acrylates such as stearyl (meth) acrylate, styrene, vinyl alcohol and the like.

  The homopolymer or copolymer can be produced by polymerizing the monomer of the essential constituent unit, or the monomer of the essential constituent unit and any monomer according to a conventional method. As such a polymerization method, for example, as described in JP-A-2001-200009, emulsion polymerization is carried out in an aqueous medium in the presence of a polymerization initiator such as azobisbutyronitrile and a nonionic surfactant. For example, dissolving the monomer in water-containing ethanol or water-containing isopropanol, and performing solution polymerization using a polymerization initiator such as azobisbutyronitrile.

  The molecular weight of the polymer containing the structural unit derived from the monomer represented by the general formula (1) as an essential structural unit is usually 10,000 to 1,000,000, preferably 30,000 to 500,000. If it is in the said range, it has a moderate viscosity and is excellent in a moisturizing effect sustainability and percutaneous absorption sustainability.

  The content of the polymer containing the structural unit derived from the monomer represented by the general formula (1) as an essential structural unit in the vesicle dispersion composition is usually 0.001 to 5.0% by mass. Yes, preferably 0.005-3.0 mass%, more preferably 0.05-2.0 mass%. Within this range, the structural stability and dispersion stability of the vesicle are improved, and a sufficient moisturizing effect and sustained percutaneous absorption can be obtained.

<1-3-2. Polymer Containing Structural Unit Derived from Monomer Represented by General Formula (2) as an Essential Structural Unit>
The polymer containing the structural unit derived from the monomer represented by the general formula (2) used in this embodiment as an essential structural unit contains a phosphorylcholine group in the essential structural unit. Since R ³ is a hydrogen atom or a methyl group, the essential structural unit of the polymer is
Contains a (meth) acryloyl group. That is, the essential structural unit contained in the polymer is 2- (meth) acryloyloxyethyl phosphorylcholine, preferably 2-methacryloyloxyethyl phosphorylcholine.

The polymer containing the structural unit derived from the monomer represented by the general formula (2) as an essential structural unit may be a homopolymer obtained by polymerizing only the monomer as the essential structural unit.
Such homopolymers are already commercially available. For example, lipid HM or lipid HM-500 (both methacryloyloxyethyl phosphorylcholine homopolymer (molecular weight 50,000 to 200,000); manufactured by NOF Corporation) Is mentioned.

  In addition, a polymer containing a structural unit derived from the monomer represented by the general formula (2) as an essential structural unit may share any other monomer as a structural unit as long as the effect of the essential structural unit is not hindered. The copolymer may be a polymerized copolymer. In that case, the content of the essential constituent unit in the copolymer is usually 50% by mass or more, preferably 60% by mass or more. In addition, in a vesicle dispersion composition, a seed | species can also be contained among the said homopolymer and the said copolymer, and it can also contain in combination of 2 or more type.

  When the polymer containing the structural unit derived from the monomer represented by the general formula (2) as an essential structural unit is a copolymer, examples of the optional monomer include the above <1-3-1>. Any of the described monomers can be used. Moreover, the said homopolymer or copolymer can be manufactured, for example with the manufacturing method etc. which were described in said <1-3-1>.

  Examples of the copolymer include (meth) acryloyloxyethyl phosphorylcholine / butyl (meth) acrylate copolymer, (meth) acryloyloxyethyl phosphorylcholine / stearyl (meth) acrylate copolymer, and the like. Such copolymers are already commercially available, and examples thereof include lipid PMB (2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer (molecular weight 600,000); manufactured by NOF Corporation).

  The molecular weight of the polymer containing the structural unit derived from the monomer represented by the general formula (2) as an essential structural unit is usually 10,000 to 1,000,000, preferably 30,000 to 500,000. If it is in the said range, it has a moderate viscosity and is excellent in a moisturizing effect sustainability and percutaneous absorption sustainability.

  Further, the content of the polymer containing the structural unit derived from the monomer represented by the general formula (2) as an essential structural unit in the vesicle dispersion composition is usually 0.001 to 5.0% by mass. Yes, preferably 0.005-3.0 mass%, more preferably 0.05-2.0 mass%. Within this range, the structural stability and dispersion stability of the vesicle are improved, and a sufficient moisturizing effect and sustained percutaneous absorption can be obtained.

<1-4. Vesicle dispersion composition>
In the vesicle dispersion composition according to this embodiment, the vesicle having a lipid bilayer structure having phospholipid and ceramide as constituents is a constituent unit derived from the monomer represented by the general formula (1) as an essential constituent unit. And an aqueous phase containing one or two or more polymers selected from the group consisting of a polymer containing as a required constituent unit a polymer derived from the monomer represented by formula (2) as an essential constituent unit It is dispersed in the inside. The appearance varies depending on the composition and blending amount, but is either transparent, translucent or opaque. Moreover, although it is a viscous liquid form from a low-viscosity liquid, this may also exhibit a gel form by the composition and compounding quantity.
Since the vesicle dispersion composition according to this embodiment is excellent in moisturizing effect and durability of percutaneous absorption, it is preferably used for external preparations for skin such as pharmaceuticals and cosmetics, and particularly preferably used for cosmetics.

<1-5. Active ingredient>
The vesicle dispersion composition according to this embodiment can contain an active ingredient. Examples of these active ingredients include plant extract, whitening ingredient, anti-inflammatory ingredient and the like as follows.

<1-5-1. Plant extract>
The aspect in which the vesicle dispersion composition which concerns on this embodiment contains a plant extract is also preferable. The plant extract is not particularly limited as long as it is generally used for pharmaceuticals, cosmetics and the like. For example, akebi extract, asunaro extract, asparagus extract, avocado extract, achacha extract, almond extract, arnica extract, aloe extract, apricot extract, ginkgo biloba extract, fennel extract, ages extract, enmiso extract, oxon extract, agar extract, auren Extract, ginseng extract, hypericum extract, nettle extract, orange extract, oyster extract, cuckoo extract, chamomile extract, carrot extract, kawara mugi extract, licorice extract, kiwi extract, cucumber extract, guava extract, cucumber extract, gardenia extract, kumazasa extract, clara Extract, walnut extract, grapefruit extract, black rice extract, chlorella extract, mulberry extract, ghetto extract, gentian Kiss, Genno pepper extract, Black tea extract, Burdock extract, Rice extract, Rice fermented extract, Rice bran fermented extract, Rice germ oil, Cowberry extract, Salvia extract, Soap extract, Sasa extract, Hawthorn extract, Sansha extract, Salamander extract, Shiitake extract, Giant extract, lion extract, perilla extract, linden extract, citrus extract, peony extract, ginger cucumber extract, ginger root extract, birch extract, cedar extract, stevia extract, stevia fermented product, crocodile extract, hawthorn essence, elderberry extract, yarrow Extract, mint extract, sage extract, mallow extract, nematode extract, assembly extract, Sorakuhi extract, Daiou extract, soybean extract , Tiso extract, thyme extract, dandelion extract, tea extract, clove extract, chimpi extract, bonito tea extract, pepper extract, touki extract, citrus extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic Extract, Novara extract, Hibiscus extract, Bakumondo extract, Lotus extract, Parsley extract, Birch extract, Hamamelis extract, Butterberry extract, Cypress extract, Biwa extract, Buffalo dandelion extract, Buffalo extract, Bukcho extract, Butcher bloom extract, Grape extract, Grape seed extract , Loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, maroonnier extract, mizubasho Extract, Mukuroji Extract, Melissa Extract, Mozuku Extract, Peach Extract, Cornflower Extract, Eucalyptus Extract, Yukinoshita Extract, Yuzu Extract, Lily Extract, Yokuinin Extract, Artemisia Extract, Lavender Extract, Green Tea Extract, Apple Extract, Rooibos Tea Extract, Ganoderma Extract, Lettuce Extract , Lemon extract, forsythia extract, forsythia extract, rose extract, rosemary extract, roman chamomile extract, royal jelly extract, bitumen extract and the like.
Content of the plant extract in a vesicle dispersion composition is 0.001-20 mass% normally, Preferably it is 0.005-15 mass%, More preferably, it is 0.01-10 mass%.

<1-5-2. Whitening ingredients>
The embodiment in which the vesicle dispersion composition according to this embodiment contains a whitening component is also preferable. The whitening component is not particularly limited as long as it is generally used for pharmaceuticals, cosmetics and the like. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethylascorbic acid, tranexamic acid, arbutin, 2-[(triphenylmethyl) oxy] ethanol, 1- (triphenylmethyl) piperidine, N -(P-toluyl) cysteic acid,
N- (p-methoxybenzoyl) cysteic acid and the like can be mentioned. Some of these whitening components are already on the market, or they can be obtained by synthesis. For example, 3-O-ethylascorbic acid can be synthesized by a known method described in JP-A-8-134055. There are also commercially available products (“VC ethyl” manufactured by Nippon Seika Co., Ltd.), and these can be obtained and used. 2-[(Triphenylmethyl) oxy] ethanol and 1- (triphenylmethyl) piperidine are disclosed in Patent Document WO 2010-074052 as N- (p-toluyl) cysteic acid and N- (p-methoxybenzoyl). Cysteinic acid is WO20
Since the synthesis method is disclosed in the pamphlet of No. 10-058730, it can be synthesized according to the disclosure.
Content of the whitening component in a vesicle dispersion composition is 0.001-25 mass% normally, Preferably it is 0.005-20 mass%, More preferably, it is 0.01-15 mass%.

<1-5-3. Anti-inflammatory component>
It is also preferable that the vesicle dispersion composition according to this embodiment includes an anti-inflammatory component. Examples of the anti-inflammatory component include clarinone, grabridine, glycyrrhizic acid, glycyrrhetinic acid, and the like, and preferred are glycyrrhizic acid and its salt, glycyrrhetinic acid alkyl and its salt, and glycyrrhetic acid and its salt.
Content of the anti-inflammatory component in a vesicle dispersion composition is 0.001-25 mass% normally, Preferably it is 0.005-20 mass%.

<2. Method for producing vesicle dispersion composition>
Another embodiment of the present embodiment is a method for producing the vesicle dispersion composition described above.
The production method according to this embodiment is represented by (i) a polymer containing a structural unit derived from a monomer represented by the general formula (1) as an essential structural unit in the aqueous phase and the general formula (2). A step of dispersing one or two or more polymers selected from the group consisting of polymers containing a structural unit derived from a monomer as an essential structural unit to obtain a dispersion; and (ii) the obtained dispersion And a step of dispersing a vesicle containing at least the components A and B prepared in advance as a constituent component to obtain a vesicle dispersion composition.

  As described above, the manufacturing method according to this embodiment includes a two-step process. When this is a one-step process, that is, when a mixed solution containing at least the above-described phospholipid, ceramide, and polymer is prepared without previously preparing a vesicle containing at least phospholipid and ceramide as components, This is because the components form a complex and a normal vesicle dispersion composition cannot be prepared.

  In the step of obtaining the dispersion liquid in (i) above, for example, it can be prepared by appropriately using a known preparation method. In the step (ii), in the step of obtaining a vesicle containing at least phospholipid and ceramide as constituent components, a known preparation method can be used as appropriate. In the step of dispersing the vesicle in the dispersion obtained in the step (i), the dispersion and the vesicle are heated to 40 ° C. to 100 ° C., the vesicle is added to the dispersion, and the mixture is stirred. Can be dispersed.

<3-1. Skin preparations>
Another embodiment of the present embodiment is a skin external preparation containing the vesicle dispersion composition described above or the vesicle dispersion composition produced by the production method described above.
Inclusion of the vesicle dispersion composition in an external preparation for skin enhances the persistence of the ceramide-derived moisturizing effect at the site of application, and allows percutaneous absorption of an active ingredient such as a plant extract or whitening ingredient contained in the vesicle. More lasting.
The vesicle dispersion composition according to this embodiment can be blended into a lotion, an emulsion, or a face wash. In the present specification, the external preparation for skin is not particularly limited as long as it is externally applied to the skin, and examples thereof include cosmetics including quasi-drugs, and external items for skin. Cosmetics are particularly preferred.
The external preparation for skin according to this embodiment may take any of the conventionally known emulsion dosage forms, essence dosage forms, cream dosage forms, and powder-containing dosage forms. As the cosmetic, any of basic cosmetics, hair cosmetics, and makeup cosmetics can be applied, but it is particularly preferable to apply to basic cosmetics. In the external preparation for skin according to this embodiment, the content of the vesicle dispersion composition is usually 0.1 to 50% by mass, preferably 0.5 to 40% by mass, more preferably 1 to 30% by mass. %.

<3-2. Ingredients>
In the external preparation for skin according to this embodiment, in addition to the above-mentioned active ingredients, optional ingredients that are usually used in cosmetics and external preparations for skin can be contained. Examples of such optional components include hydrocarbons such as liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax, oleic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behen. Acids, higher fatty acids such as undecylenic acid, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, higher alcohols such as cetostearyl alcohol, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane Cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, etc. Oils such as silicone oils such as siloxane, amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, and fluorine-modified polysiloxane, fatty acid soap (sodium laurate, sodium palmitate, etc.), lauryl Anionic surfactants such as potassium sulfate, alkyl sulfate triethanolamine ether, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, betaine surfactants (alkyl betaines, amide betaines, Amphoteric surfactants such as sulfobetaine), imidazoline-based amphoteric surfactants (such as 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt), and acylmethyl taurine Surfactants, sorbitan fatty acid esters (such as sorbitan monostearate, sorbitan sesquioleate), glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hydrogenated castor oil Derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polystearic acid polyoxyethylene sorbitan, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid esters (POE) -Glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE) -Octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil, Hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), nonionic surfactants such as sucrose fatty acid ester, alkyl glucoside, polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, Maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, 1,2-octanedi Polyhydric alcohols such as alcohol, moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxy Ethyl cellulose, carboxymethyl cellulose, methyl hydroxypropyl cellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato sulfate , Locust bean gum, succinoglucan, caronic acid, chitin, chitosan, carboxymethyl chitin, cold Tenki, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, thickener such as sodium polyacrylate, polyethylene glycol, bentonite, surface may be treated, mica, talc, kaolin, synthetic mica , Calcium carbonate, magnesium carbonate, silicic anhydride (silica), powders such as aluminum oxide, barium sulfate, surface may be treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen Inorganic pigments such as titanium oxide and zinc oxide, surface may be treated, pearl agents such as titanium mica, fish phosphorus foil, bismuth oxychloride, may be raked, red No. 202, red 228 No., Red No. 226, Yellow No. 4, Blue No. 404, Yellow No. 5, Red No. 505, Red 230, red 223, orange 201, red 213, yellow 204, yellow 203, blue 1, green 201, purple 201, red 204, organic dyes, polyethylene powder, polymethacrylic acid Organic powders such as methyl, nylon powder, organopolysiloxane elastomer, paraaminobenzoic acid UV absorber, anthranilic acid UV absorber, salicylic acid UV absorber, cinnamic acid UV absorber, benzophenone UV absorber, Sugar-based UV absorber, 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 4-methoxy-4′-t-
Ultraviolet absorbers such as butyldibenzoylmethane, lower alcohols such as ethanol and isopropanol, vitamin A or its derivatives, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or its derivatives Vitamin B ₁₂ such as vitamin B ₁₂ , vitamin B ₁₅ or a derivative thereof, α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, Preferred examples include vitamins such as pyrroloquinoline quinone.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example, it cannot be overemphasized that this invention is not limited only to a following example.

<Examples 1-4 and Comparative Examples 1-3>
A vesicle dispersion composition of the present invention was prepared based on the formulation described in Table 1. That is, component (a) was heated and stirred at 90 ° C. to obtain a uniform solution. Then, after stirring using a disper, it cooled to room temperature and the vesicle dispersion liquid was prepared. The component (b) was stirred and mixed at room temperature to obtain a uniform solution, and the vesicle dispersion was added thereto, and finally a vesicle dispersion composition (hereinafter also simply referred to as “vesicles 1 to 7”) was prepared. . In addition, the molecular weight of polymethacryloyl lysine is 50,000 to 200,000, and the molecular weight of polymethacryloyloxyethyl phosphorylcholine is 50,000 to 200,000. The numbers in the table represent mass%.

<Examples 5 to 8>
In Examples 1 to 4, the components (I) and (B) listed in Table 1 were heated at 90 ° C. and mixed with stirring to obtain a solution. Then, after stirring using a disper, it cooled to room temperature and finally prepared a vesicle dispersion composition (hereinafter also simply referred to as “vesicles 8 to 11”).

<Test Example 1 Transdermal absorbability evaluation of vesicle dispersion composition>
Three parts of 1 cm × 1 cm were provided in the inner part of the forearm of the volunteer paneler, 7 μL of the vesicles 1 to 11 prepared above were applied to each, and allowed to stand at 20 ° C. for 1 hour, and then impregnated with tetrahydrofuran (THF). Site 1 was wiped off with absorbent cotton, and this absorbent cotton was extracted three times with 100 ml of THF, and the recovered amount of centauridin derived from yarrow contained in the extract was quantified by high performance liquid chromatography. The percutaneous absorption rate was calculated using the following equation, where the amount of centerurein contained in the applied vesicle was W0 and the amount of centerureidine recovered was Wi. The same measurement was performed at the remaining vesicle application site after 3 hours and 6 hours. The results are shown in Table 3.
Percutaneous absorption rate = {(W0−Wi) / W0} × 100

<Test Example 2 Measurement of TEWL recovery rate>
The inner side of the forearm of a volunteer paneler was washed with water, dried, and the transdermal water transpiration (TEWL) was measured using a tevameter (Tewameter TM210 Courage + Khazaka). Thereafter, after treatment with a 0.1% aqueous solution of sodium lauryl sulfate (hereinafter also referred to as “SLS”) and washing with water again, vesicles 1 to 11 were applied, and the same after 6 hours, 12 hours and 24 hours. The site TEWL was measured. The value of the vesicle application site when TEWL before SLS treatment was set to 100 was determined as the recovery rate. The results are shown in Table 4. The closer the number is to 100, the more TEWL is recovered.

<Test Example 3 Evaluation of Storage Stability>
Vesicles 1 to 11 were stored at 40 ° C. for 1 month, the appearance was observed with the naked eye, and the particle size of the vesicles was measured with a Coulter counter. The results are shown in Table 5 in comparison with those immediately after the preparation of the vesicle dispersion composition.

<Examples 9 to 12>
According to the formulation of Table 6, creams and emulsions, which are external preparations for skin of the present invention, were prepared. That is, component (a) was heated to 75 ° C. and mixed with stirring. While continuing to stir at 75 ° C., component (b) was slowly added. Then, while continuing stirring, after adding component (c), emulsifying using a homomixer, adding component (2), cooling to room temperature, adding component (e), cream And an emulsion was obtained. In addition, the numerical value in Table 6 represents the mass%.
For the creams and emulsions of Examples 9 to 12, the percutaneous absorption rate and the TEWL recovery rate were measured in the same manner as in Test Examples 1 and 2. The results are shown in Table 7 and Table 8.

  The present invention relates to a preparation technique useful for an external preparation for skin, and more specifically, can be applied to a preparation technique using a vesicle dispersion composition.

Claims (5)

A vesicle dispersion composition comprising: a vesicle containing at least the following components A and B as constituent components; and component C.
A) a phospholipid B) ceramide C) a polymer containing a structural unit derived from the monomer represented by the general formula (1) as an essential structural unit, and a structural unit derived from the monomer represented by the general formula (2) One or two or more polymers selected from the group consisting of polymers containing as essential constituent units

(In the general formula (1), R ¹ represents a hydrogen atom or a methyl group, R ² represents an amino acid residue, a polyamine residue or an amino alcohol residue. X represents an oxygen atom or a group represented by NH. )

(In general formula (2), R ³ represents a hydrogen atom or a methyl group.)   The vesicle dispersion composition according to claim 1, wherein the phospholipid is lecithin.   Furthermore, the vesicle dispersion composition of Claim 1 or 2 containing a plant extract. A method for producing a vesicle dispersion composition according to any one of claims 1 to 3,
(I) a step of dispersing the component C in an aqueous phase to obtain a dispersion; and
(Ii) a step of dispersing a vesicle containing at least the components A and B prepared in advance as constituents in the obtained dispersion to obtain a vesicle dispersion composition;
Manufacturing method.   The skin external preparation containing the vesicle dispersion composition of any one of Claims 1-3, or the vesicle dispersion composition manufactured by the manufacturing method of Claim 4.