KR102100311B1 - Vesicle composition, and external preparation for skin and cosmetic preparation each of which contains same - Google Patents

Abstract

(Task) To provide a vesicle composition excellent in aging stability and skin permeability, and excellent skin affinity when used, and an external preparation for skin and a cosmetic composition containing the same.
(Solution) The following components (A) to (D); (A) Phospholipids (B) One or two or more selected from cholesterol and phytosterols (C) Cationic surfactants (D) A vesicle composition containing a polypeptide mainly composed of a basic amino acid and an external preparation for skin and a cosmetic comprising the same .

Description

VESSICLE COMPOSITION AND SKIN EXTERMINATION AND COSMETIC COMPOSITIONING THE SAME TECHNICAL FIELD TECHNICAL FIELD OF WHICH CONTAINS SAME

The present invention, component (A) phospholipid (燐 脂質), component (B) cholesterol (cholesterol) and one or two or more selected from phytosterol (phytosterol), component (C) cationic surfactant (cationability 界面 活性) Iii), component (D) It relates to a vesicle composition containing a polypeptide mainly composed of a basic amino acid and an external preparation for skin and a cosmetic comprising the same.

Conventionally, as a method of blending a non-water-soluble active ingredient in a skin external preparation or cosmetic, a method of dispersing the water-insoluble active ingredient as a vesicle particle in a water-based solvent is widely used.

Normally, vesicles were produced by dispersing the vesicle main component and active ingredient in a water-based solvent, followed by sonication or high pressure treatment. In addition, the main component of the vesicle is composed of a surfactant, and the aging stability of the vesicle itself (long-term stability) was dependent on the molecular power of the surfactant. Therefore, the vesicle is easily affected by the external environment, and aggregation, etc. occurs, and thus the stability over time is not good. Therefore, the development of a vesicle with excellent stability over time has been required.

As an amphiphilic substance constituting the vesicle to improve the stability with time of the vesicle, for example, a natural origin of phospholipids as a raw material and the second acyl group (2 位 acyl base) is unsaturated Phospholipid derivatives, which are residues of fatty acids, are known (for example, see Patent Document 1).

In addition, as a technique for improving the stability over time of the vesicle, the average particle size is 100∼ using hydrogenated soybean phospholipids having a phosphatidyl choline content of 90% by weight or more and an iodine vaule of 0.1 or less. A cosmetic vesicle adjusted to 500 nm (for example, see Patent Document 2), a film-forming material of a vesicle selected from phospholipids, sucrose fatty acid esters and acyl amino acid salts As a vesicle composition containing one or two or more of the above and a water-soluble polymer, a vesicle composition (for example, refer to Patent Document 3) obtained by allowing a water-soluble polymer to be present at the time of vesicle formation and subjected to high pressure treatment is known. there was.

On the other hand, some of the active ingredients have low skin permeability, and there is a demand for a technology that can penetrate skin efficiently. For example, to a liposome composed of phospholipids, at least to a part of its structure, as a substance or a mixture that promotes the intracellular penetration of the active ingredient, the substance or a mixture thereof is of the formula RN (R ₁ R ₂ R ₃ Includes quaternary plant proteins in the form (wherein R is a symbol for a plant protein molecule; R ₁ and R ₂ are independently C1 to C6 hydrocarbon groups, and R ₃ is an alkyl group having 10 to 18 carbon atoms). By doing so, there is a technique to increase intracellular penetration (for example, see Patent Document 4).

Patent Document 1: Japanese Patent Application Publication No. 2008-88133 Patent Document 2: Japanese Patent Application Publication No. 2006-124378 Patent Document 3: Japanese Patent Application Publication No. 2008-94808 Patent Document 4: Japanese Patent No. 4950419

The present invention is to provide a cosmetic composition and an external preparation for skin and a cosmetic composition comprising the vesicle composition and excellent aging stability and skin permeability and excellent compatibility with skin when used.

As a result of repeated studies of the present inventors, a method of adding a water-soluble polymer in the production of a vesicle described in Patent Document 3 is insufficient with stability over time only by using a specific phospholipid described in Patent Document 2. , There was a case where the texture of the water-soluble polymer was constrained in terms of feeling. In addition, in the method of containing the quaternized plant protein described in Patent Document 4, there was a problem with respect to stability over time, such as odor discoloration.

As a result of repeated studies in view of these circumstances, the present inventors further combined a phospholipid, a polypeptide formed by one or two or more selected from cholesterol and phytosterol, and a polypeptide mainly composed of a basic amino acid, The polypeptide promotes the adsorption of vesicles in the stratum corneum, effectively penetrates the vesicle formed by phospholipids and one or two or more selected from cholesterol and phytosterols, and effectively penetrates the skin, and has affinity for the skin during use. We found that this became good.

However, when a vesicle formed by one or two or more selected from phospholipids, cholesterol, and phytosterols is combined with a polypeptide mainly composed of a basic amino acid, stability over time in cosmetics or external preparations for skin is deteriorated, resulting in problems such as aggregation. Occurred.

Therefore, as a result of further examination by the present inventors, by using a cationic surfactant in combination with a polypeptide mainly composed of one or two or more selected from phospholipids, cholesterol and phytosterols, and a basic amino acid, the cationic surfactant is obtained. Phospholipids, one or two or more selected from cholesterol and phytosterols, and improve the dispersibility of the vesicle comprising the polypeptide, not only improve the stability over time, but also improve the skin permeability and use of the vesicle. It was found that the skin affinity was also improved, and the present invention was completed.

Specifically, the present invention provides the following components (A) to (D);

(A) Phospholipid

(B) One or two or more selected from cholesterol and phytosterol

(C) cationic surfactant

(D) a polypeptide mainly composed of basic amino acids

It is to provide a containing vesicle composition.

Moreover, this invention provides the said vesicle composition in which the said component (C) is a cationic surfactant which has an amino acid residue.

Moreover, this invention provides the said vesicle composition whose said component (C) is a mono-N-long chain acyl basic amino acid lower alkyl ester salt.

Moreover, this invention provides the said vesicle composition whose number average molecular weight of the said component (D) is 1500-10000.

Moreover, this invention provides the said vesicle composition in which the basic amino acid of the said component (D) is 1 or 2 types or more selected from arginine, lysine, and histidine.

Moreover, this invention provides the said vesicle composition whose ratio of the basic amino acid of the said component (D) is 60% mol or more.

Moreover, this invention provides the said vesicle composition whose said component (C) is N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate.

Moreover, this invention provides the said vesicle composition whose said component (D) is polylysine.

Moreover, this invention provides the said vesicle composition whose pH at 25 degreeC is in the range of 3.0-6.5.

Moreover, this invention provides the said vesicle composition whose ζ potential at 25 degreeC is 5-100.

It is also to provide an external preparation for skin and a cosmetic comprising the vesicle composition.

According to the present invention, by combining one or two or more selected from phospholipids, cholesterol, and phytosterols, a cationic surfactant, and a polypeptide mainly composed of a basic amino acid, excellent stability over time and skin permeability, and skin affinity when used It is possible to provide this excellent vesicle composition and an external preparation for skin and a cosmetic comprising the vesicle composition.

Fig. 1 is a photographic replacement photograph showing confocal laser microscope observation results in a three-dimensional skin model of the vesicle composition of the present technology.
FIG. 2 is a photographic diagram showing the results of observation of a confocal laser microscope in a three-dimensional skin model of the vesicle composition of Comparative Example.

The present technology, component (A) phospholipid (燐 脂質), component (B) cholesterol (cholesterol) and one or two or more selected from phytosterol (phytosterol), component (C) cationic surfactant (cationability 界面 活性) Iv), component (D) a vesicle composition containing a polypeptide mainly composed of a basic amino acid and a skin external preparation containing the same; and It is a cosmetic.

Hereinafter, the present technology (the present invention) will be described in detail. In addition, in this specification, "-" shall mean the range containing the numerical value before and after that.

The phospholipid of the component (A) used in the present technology is used as a component of the vesicle in the present technology, and is not particularly limited as long as it is used in ordinary cosmetics, external preparations for skin, and the like. Preferred specific examples include phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl glycerol, phosphatidyl inositol, phosphatidyl inositol, phosphatidyl inositol, sphingolipid And one or two or more selected from them.

Further, as the component (A), a composition containing one or two or more of the phospholipids as described above may be used. As the composition containing the phospholipids, for example, soybean lecithin (also referred to as "soybean phospholipid"), egg yolk lecithin (also referred to as "yellow yolk phospholipid") and their hydrogenated products, they can be removed by enzymatic treatment. And lysolecithin, which has been digested. Among them, it is preferably a hydrogenated phospholipid, and more preferably a hydrogenated soybean phospholipid.

These may be used alone or in combination of two or more appropriately selected as necessary.

Specific products include YSL-70 provided by YEM CO., LTD, NIOL lecinol S-10E provided by Nikko Chemicals, and Nisshin OilliO Group LBS-60BR provided by Group, and egg yolk lysolecithin LPC-1 provided by Kewpie.

Although the content of the component (A) in the present technology is not particularly limited, 0.01 to 5% by mass in the vesicle composition is preferred from the viewpoint of stability over time and compatibility with skin, and 0.05 to 4 mass% is more preferable from a viewpoint of stability with time, and 0.1-2 mass% is more preferable.

One or two or more selected from cholesterol and phytosterol of the component (B) used in the present technology contribute to the stability of the bimolecular film structure in vesicle formation, and by containing this, stability over time can be improved. . Cholesterol and phytosterol can also be used in combination.

Cholesterol is generally purified from natural products, and cholesterol purified from any natural product can be used in the present technology.

Phytosterols can be generally used as long as they are classified as phytosterols (vegetable sterols), and preferably contain camphorol, sitosteol, stigmastanol, etc. as components. Can be illustrated. These components can be obtained by extracting the germ or the like of the grains with an organic solvent and removing the water-soluble portion, but it is also possible to purchase and use commercially available ones.

In the present technology, the content of the component (B) is not particularly limited, but 0.01 to 5% by mass in the vesicle composition is preferred from the viewpoint of stability over time and skin affinity, and 0.05 to 3% by mass Is more preferable from the viewpoint of skin affinity, and more preferably 0.05 to 1% by mass.

Moreover, it is preferable to set the content mass ratio ratio of a component (A) and a component (B) from 1: 1 to 1: 1.

The cationic surfactant of the component (C) used in the present technology has the effect of improving the dispersibility of the vesicle and improving the skin permeability and the skin affinity when used.

The cationic surfactant of component (C) in the present technology is not particularly limited and can be used as long as it is used in ordinary cosmetics, external preparations for skin, and the like.

As component (C), for example, cetyl trimethylammonium chloride, cetyl trimethylammonium bromide, stearyl trimethylammonium chloride, stearyl trimethylammonium bromide, behenyl trimethylammonium chloride, behenyl trimethylammonium bromide, behenyl trimethylammonium methyl sulfate, Distearyl dimethylammonium chloride, dimethylammonium bromide, cetyl behenyl methylsulfate dimethylammonium, stearyl dimethylbenzylammonium chloride, dipalmitoyl ethylhydroxy ethylmoniummethosulfate, dicoyl ethylhydroxy ethyl Quaternary ammonium salts such as ammonium methosulfate (dicocoyl ethylhydroxy ethylmoniummethosulfate) and distearoyl ethylhydroxy ethylmoniummethosulfate; Mono-N-long-chain acyl basic amino acid lower alkyl such as stearoylcin butyl ester, hydrochloride, N-palm fatty acid acyl L-arginine ethyl, DL-pyrrolidone carboxylate, lauroyl-ornithine propyl ester, acetate, etc. Ester salts (mono-N-long chain acyl 鹽基 性 amino acid 低級 alkylester 鹽); Guanidine derivatives, such as decylguanidine acetate, 2-guanidinoethyl lauryl amide hydrochloride, and 2-guanidinobutyl stearoamide-DL-pyrrolidone carboxylate, etc. can be illustrated, From these, 1 type or 2 You can choose more than one species. In addition, examples of these salts include halogen, methosulfate, ethosulfate, and methophosphate.

Among these, in the present technology, quaternary ammonium salts and mono-N-long-chain acyl basic amino acid lower alkyl ester salts are preferred. In addition, among the quaternary ammonium salts, di-long chain acyl alkylhydroxy alkylammonium salts (e.g., dipalmitoyl ethylhydroxy ethylmonium methosulfate, dicocoyl ethylhydroxy ethylmonium methosulfate) And distearoyl ethylhydroxy ethylmonium methosulfate, etc.) are preferred.

The carbon number of the "long chain acyl" in the "dilong chain acyl alkylhydroxy alkyl ammonium salt" and "mono-N-long chain acyl basic amino acid lower alkyl ester salt" is preferably 10 to 30, and further It is preferably 8 to 22. In addition, "long-chain acyl" refers to mixed fatty acids of a plant type (for example, laurin-based fats and oils such as palm oil and palm kernel oil), or animal-based mixed fatty acids (for example, Uji) It may be derived from fatty acids (eg, beef fat). As a fatty acid which becomes a "long-chain acyl", for example, lauric acid, myristic acid, palmitic acid, linoleic acid, oleic acid, linolenic acid ( linolenic acid), stearic acid, and the like, and one or two or more of them can be selected and used. Moreover, in the case of "dilonged acyl", these may be the same or different.

Further, the number of carbon atoms of the "alkyl", "hydroxyalkyl" and "lower alkyl" is preferably 1 to 7, more preferably 1 to 5, and as the "alkyl" and "lower alkyl", for example Methyl, ethyl, propyl, and butyl.

In addition, examples of the "basic amino acid" include lysine, arginine, histidine, ornithine, and derivatives thereof.

Also, among the cationic surfactants, cationic surfactants having amino acid residues are preferred. The surfactant used in the present technology may be one having cationic properties in the vesicle composition. As the cationic surfactant having an amino acid residue, it is preferable that the amino acid residue is a basic amino acid residue. As a cationic surfactant having an amino acid residue, a surfactant having an L-arginine residue (also referred to as "L-arginine surfactant") is suitable. In the case of an L-arginine-based surfactant, an amphoteric surfactant may be used as long as it is cationic in the vesicle composition.

In addition, as a cationic surfactant having an amino acid residue in the present technology and as an L-arginine-based surfactant, for example, it is sold as AmiSafe LMA-60 (trade name: Ajinomoto Co., Inc.). N- [3-alkyl (C ₁₂ and C ₁₄ ) oxy-2-hydroxy propyl alcohol] -L-arginine hydrochloride 2% aqueous solution, but N-coil sold as CAE (trade name: manufactured by Ajinomoto)- And L-arginine ethyl ester pyrrolidone carboxylate. N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate is preferred. The use of one or two or more selected from these is preferable since it not only improves stability with time but also becomes a vesicle composition excellent in skin permeability.

The content of the component (C) in the present technology is not particularly limited, but 0.001 to 1.0 mass% in the vesicle composition is preferable from the viewpoint of stability with time and skin permeability, and more preferably 0.02 to 0.5 mass% , 0.005 to 0.5% by mass is more preferable from the viewpoint of skin permeability.

The polypeptide mainly composed of the basic amino acid of the component (D) used in the present technology has an effect of improving the skin penetration of the vesicle and the skin affinity when used. The basic amino acid is, for example, arginine, lysine, histidine and ornithine (usually using an L-type), and skin affinity is achieved when a polypeptide mainly composed of one or two or more selected from basic amino acids is used. It is preferable because it becomes an excellent vesicle composition. A polypeptide mainly composed of basic amino acids has a ratio of basic amino acids in the polypeptide of 60% mol or more, preferably 70% mol or more, more preferably 80% mol or more, and more preferably 90% mol or more.

Moreover, although the number average molecular weight of the polypeptide of component (D) varies with amino acids, 1500-10000 is preferable. In addition, the number average molecular weight of the polypeptide of component (D) can be calculated from a chart of high performance liquid chromatography (HPLC).

Also, among the polypeptides mainly composed of the basic amino acid, polylysine, polyhistidine and the like are preferred. The use of one or two or more selected from these is preferable because it is a vesicle composition excellent in skin penetration and skin affinity when used.

As a commercial product of the polypeptide, polylysine 10 represented by Polyepsilon-Lysine as an International Nomenclature Cosmetic Ingredient labeling names (an aqueous solution containing 10% polylysine (manufactured by Ichimarupharcos)), etc. can be used. You can.

The content of the component (D) in the present technology is not particularly limited, but 0.001 to 5.0% by mass in the vesicle composition is preferred from the viewpoint of skin permeability and temporal stability, and 0.005 to 1.0% by mass is stable over time. It is more preferable from a viewpoint, and 0.025 to 0.1 mass% is more preferable.

Moreover, the vesicle composition of this technology contains water in addition to the said components (A)-(D). Since water is used as a dispersion medium for the above components, it is an essential component as a vesicle composition. The content of water in the present technology is appropriately determined by a person skilled in the art depending on the content of components (A) to (D), but is preferably approximately 60 to 95% by mass in the vesicle composition. As such water, distilled water derived from plants such as purified water, hot spring water, rose water or lavender water can be used. One or two or more of them may be used.

In addition, in the process of forming the vesicle, it is necessary to keep the dispersibility of the components (A) to (D) (especially components (A) and (B)) satisfactory, for the purpose of improving the dispersibility of each component, Propylene glycol, 1,3-butylene glycol, dipropylene glycol, 1,2-pentanediol, glycerin, Polyhydric alcohols such as diglycerin and sorbitol may be added to the medium. It is preferable that content of the polyhydric alcohol in this technique is 1-20 mass% in a vesicle composition.

In addition, the vesicle composition of the present technology does not impair the effects of the present technology, alcohols, emulsions, surfactants, thickeners, powders, chelating agents other than the above components , pH adjusters, ultraviolet absorbers, plant-derived microorganism-derived extracts, moisturizers, anti-inflammatory agents, cell-activating agents, etc., may be variously added. In addition, various additives may be added at the time of vesicle production or may be added after vesicle production. In addition, the vesicle may be enclosed or not enclosed.

In addition, the vesicle composition of the present technology is preferable because it improves aging stability and skin permeability by increasing the ζ potential. The ζ potential is not particularly limited, but is preferably 5 to 100 (more preferably 7 or more and 80 or less, and more preferably 10 or more and 50 or less) because stability with time is more excellent. The ζ potential is a value measured at a temperature of 25 ° C. using an electrophoretic light scattering photometer LEZ-600 manufactured by Otsuka Electronics Co., Ltd.

In addition, the pH of the vesicle composition of the present technology is not particularly limited, but the pH at 25 ° C is within the range of 3.0 to 6.5 (suitably 3.5 to 5.0) in order to increase the ζ potential and improve the stability with time and skin penetration. It is preferred.

The method for manufacturing the vesicle composition of the present technology is not particularly limited, and can be produced by a general method. For example, the vortexing method (ADBangham, J.Mol.Biol., 13, 238 (1965)), sonication method (C.Huang, Biochem., 8, 344 (1969) ], Prevesicle method [H.Trauble, Neurosci.Res.Prog.Bull., 9, 273 (1971)], ethanol injection method [S.Batzri, Biochem.Biophys.Acta., 298, 1015 (1973) )], French press extrusion method (Y.Barenholz, FEBS Lett., 99, 210 (1979)], cholic acid method [Y.Kagawa, J.Biol.Chem. , 246, 5477 (1971), Triton X-100 batch method (WJGerritsen, Eur.J.Biochem., 85, 255 (1978)), Ca2 + fusion method [D.Papahadojopoulos, Biochem .Biophys.Acta., 394, 483 (1975)], ether injection method [D.Deazer, Biochem.Biophys.Acta., 443, 629 (1976)], annealing method [R.Lawaczeck, Biochem.Biophys .Acta., 443, 313 (1976)], freeze-thawing fusion method [M.Kasahara, J.Biol.Chem., 252, 7384 (1977)], W / O / W emulsion method [S.Matsumoto, J. Colloid Interface Sci., 62, 149 (1977)), reverse phase evaporation method ) [F.Szoka, Proc.Natl.Acad.Sci.USA, 75, 4194 (1978)], polyhydric alcohol or the like can be produced by method [Japanese Patent Application Laid-Open No. 60-7932 Patent places.

As a method for producing the vesicle composition of the present technology, for example, the above components (A) and (B) are used as the main membrane constituents of the vesicle particles, and these components (A), (B), and component ( And a mixture of C) and component (D), as well as other suitable optional components, which are appropriately heated, mixed, and cooled to obtain a vesicle composition. The temperature conditions when heating and mixing are preferably 60 to 100 ° C.

Moreover, the content mass ratio of [component (A) + component (B)]: component (C) is preferably 1: 0.001 to 1, and more preferably 1: 0.01 to 0.4.

In addition, the content mass ratio of [component (A) + component (B)]: component (D) is preferably 1: 0.001 to 1, more preferably 1: 0.01 to 0.8, further preferably 1: 0.02 to 0.08.

In addition, the content mass ratio of component (D): component (C) is preferably 1: 0.01 to 10, more preferably 1: 0.1 to 5, and further preferably 1: 1 to 4.

As an example, the component (A) and the component (B) are dispersed and dissolved in an aqueous solvent such as purified water or polyhydric alcohol at 80 ° C, and the component (C) is added to the purified water and heated and dissolved at 80 ° C. It can be obtained by adding component (D) to purified water, heating at 80 ° C. and dissolving, mixing, and gradually cooling to 40 ° C.

In addition, confirmation of vesicle formation is confirmed by the presence or absence of a maltese cross image under orthogonal nicol using a polarizing microscope, or incineration using a high-intensity incineration X-ray scattering device SAX (manufactured by Anton Paar). It can be performed by confirming a peak by X-ray scattering spectrum measurement or the like. Confirmation of vesicle formation in the vesicle composition of the present technology was performed by observing a sample under orthogonal Nicole using a polarizing microscope (manufactured by Olympus Corporation) to confirm the presence or absence of a Maltese cross.

There are no particular restrictions regarding the use of the vesicle composition of the present technology. The vesicle composition of the present technology is used for the preparation of compositions for various applications such as external preparations for skin (for example, external preparations for pharmaceuticals and quasi-drugs), cosmetics, pharmaceuticals (oral, injection, etc.) and food. Can be used. The vesicle composition of the present technology is also excellent in heat resistance, and even when blended at the time of production, it is possible to obtain the expected effect in the present technology. These compositions may be liquid, semi-liquid (including gel-like and paste-like), solid, or any other form.

The vesicle composition of the present technology is characterized by having excellent skin permeability, and from that point of view, it is preferable to use it as an external preparation for skin or a cosmetic or when preparing them.

The vesicle composition of the present technology may be used as an external preparation for skin or as a cosmetic, or may be used as an external preparation for skin or a cosmetic by containing other ingredients. When other ingredients are included to form an external preparation for skin or a cosmetic, the content of the vesicle composition of the present technology in these products is not particularly limited, but is preferably 1.0 to 90% by mass, more preferably 3.0 to 50 It is mass%.

An example of a method for manufacturing an external preparation for skin or a cosmetic using the vesicle composition of the present technology is as follows. It is a method for preparing an external preparation for skin or a cosmetic product, including preparing the vesicle composition of the present technology and mixing the vesicle composition with an active ingredient.

The pH of the skin external preparation or cosmetic to be prepared is not particularly limited, but the difference between the pH at the time of preparing the vesicle composition and the pH of the skin external preparation or cosmetic to be produced is preferably smaller. When the difference is 1.0 or less, the shape of the vesicle is maintained even in an external preparation for skin or a cosmetic, and the dispersibility and dispersibility with time are maintained satisfactorily.

There is no particular limitation on the formulation of the external preparation for skin or cosmetic of the present technology. Liquid, semi-liquid and solid phases may be used. Examples include various external skin preparations or cosmetic products such as latex, cream, lotion, cosmetic liquid, pack, face wash, make-up cosmetic, and ointment. have. In addition, the skin external preparation or cosmetic of the present technology, in addition to the vesicle composition of the present technology, various ingredients commonly used in external skin preparations or cosmetics, namely alcohol, emulsion, surfactant, thickener, powder, chelating agent, pH adjuster, ultraviolet absorber, plant · Microorganism-derived extracts, moisturizers, anti-inflammatory agents, cell activators, and other medicinal agents, fragrances, and the like can be appropriately added within a range that does not impair the effectiveness of the present technology.

The efficacy of the vesicle in the external preparation for skin or cosmetic of the present technology is not particularly limited. Becyclocyclo made of phospholipids is characterized by excellent skin permeability. In addition, the active ingredient may be included in the vesicle, and in this aspect, the effect of the active ingredient in addition to the sustained-release property of the active ingredient will be obtained.

The present technology can also adopt the following structures.

[1] The following components (A) to (D);

(A) Phospholipid

(B) One or two or more selected from cholesterol and phytosterol

(C) cationic surfactant

(D) a polypeptide mainly composed of basic amino acids

Vesicle composition containing a.

[2] The vesicle composition according to the above [1], wherein the component (C) is a cationic surfactant having an amino acid residue.

[3] The vesicle composition according to the above [1] or [2], wherein the component (C) is a mono-N-long chain acyl basic amino acid lower alkyl ester salt.

[4] The vesicle composition according to any one of [1] to [3], wherein the number average molecular weight of the component (D) is 1500 to 10000.

[5] The vesicle composition according to any one of [1] to [4], wherein the basic amino acid of the component (D) is one or two or more selected from arginine, lysine and histidine.

[6] The vesicle composition according to any one of [1] to [5], wherein the ratio of the basic amino acid of the component (D) is 60% mol or more.

[7] The vesicle composition according to any one of [1] to [6], in which the component (C) is an N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate.

[8] The vesicle composition according to any one of [1] to [7], wherein the component (D) is polylysine.

[9] The vesicle composition according to any one of [1] to [8], wherein the pH is within the range of 3.0 to 6.5 at 25 ° C.

[10] The vesicle composition according to any one of [1] to [9], wherein the ζ potential is 5 to 100 at 25 ° C.

[11] The vesicle composition according to any one of [1] to [10], wherein the content of (A) is 0.01 to 5% by mass.

[12] The vesicle composition according to any one of [1] to [11], wherein the content of (B) is 0.01 to 5% by mass.

[13] The vesicle composition according to any one of [1] to [12], wherein the content of (C) is 0.001 to 1% by mass.

[14] The vesicle composition according to any one of [1] to [13], wherein the content of (D) is 0.001 to 5.0% by mass.

[15] [The component (A) + the component (B)]: The content mass ratio of the component (C) is as described in any one of [1] to [14], in which the content ratio is 1: 0.001 to 1. Vesicle composition.

[16] [The component (A) + the component (B)]: The content ratio of the component (D) is as described in any one of [1] to [15], wherein the content mass ratio of the component is 1: 0.001 to 1 Vesicle composition.

[17] The vesicle composition according to any one of [1] to [16], wherein the content ratio of the component (D): component (C) is 1: 0.01 to 10.

[18] The vesicle composition according to any one of [1] to [17], which is obtained by heating and mixing the components (A) to (D) and cooling.

[19] The above obtained by mixing the component (A) and the component (B) by heating in an aqueous solvent, adding the dissolved aqueous solvent by heating the components (C) and (D), and heating and mixing. [1] ]-[18] The vesicle composition according to any one of items. It is preferable to blend an pharmacologically acceptable additive (suitably a medicinal ingredient) upon heating mixing.

[20] An external preparation for skin or a cosmetic comprising the vesicle composition according to any one of [1] to [19] above.

[21] An external preparation for skin or a cosmetic comprising the vesicle composition according to any one of [1] to [19] above and a pharmacologically acceptable additive. The content of the vesicle composition is preferably 1 to 90%.

<Example>

Hereinafter, examples and test examples are given to specifically describe the present technology (the present invention), but the present technology (the present invention) is not limited to these examples.

Examples 1-11 and Comparative Examples 1-3: Vesicle composition

The vesicle composition of the composition shown in Table 1 and Table 2 was prepared by the following manufacturing method, and the "aging stability", "skin permeability", and "skin affinity" of each sample were evaluated by the methods shown below. And the results are shown in Table 1 and Table 2 together.

[Table 1]

[Table 2]

Note 1: GSL-70 (manufactured by YEM Corporation)

Note 2: Nisui Marine Cholesterol (manufactured by Nippon Suisan)

Note 3: 25-ＮＢＤ Ｃｈｌｏｒｅｓｔｅｒｏｌ (made by Avanti Polar Lipids)

Note 4: Phytosterol (Eisai Food & chemical)

Note 5: DEVARTV A-56 / G (manufactured by Cognis)

Note 6: Polylysine 10 (manufactured by Ichimarupacos: molecular weight: about 5000)

Note 7: CAE (made by Ajinomoto)

(Manufacturing method)

A: Components 1 to 6 were heated to 80 ° C to obtain a solution.

Components 7 to 9 and components 10 to 11 were respectively added to the solution obtained in B: A while maintaining at 75 ° C, and a dispersion was obtained by a disper mixer.

The dispersion obtained in C: B was gradually cooled to 40 ° C to obtain a vesicle composition.

[pH measurement]

The pH of each sample was measured at 25 ° C using a pH meter of a glass electrode (manufactured by HORIBA).

[ζ potential measurement]

The zeta potential of each sample was measured at 25 ° C using an electrophoretic light scattering photometer LEZ-600 manufactured by Otsuka Electronics Co., Ltd. The measurement was carried out three times and the results were expressed as the average value.

[Vicicle verification test]

Using a polarizing microscope (manufactured by Olympus), each sample immediately after preparation was observed under orthogonal nicotine to confirm the presence or absence of a Maltese cross.

[Stability over time]

With respect to aging stability, the aging stability of the vesicle was evaluated by observing a Maltese cross image with a polarizing microscope. Specifically, it was observed that the sample was allowed to stand at 50 ° C for one month based on the state immediately after preparation of each sample, and the following four-step judgment criteria (A) were used for the quantity of maltese crosses to be confirmed. It was judged.

(A) Level 4 judgment criteria

(Judgment): (Evaluation)

◎: The quantity of Maltese cross can be checked by more than 80%

○: The quantity of Maltese crosses can be checked between 60% and 80%.

△: The quantity of the Maltese cross can be checked from 30% to less than 60%

×: Less than 30% of Malta crosses can be checked

[Skin permeability]

A three-dimensional skin model (TESTSTINI LSE) manufactured by TOYOBO is placed on an aluminum tray so that PPS (pH7.4) is wetted on the dermis side, and fluorescent cholesterol (25-NBD Chloresterol, The above-mentioned Examples 1 to 11 and Comparative Examples 1 to 3 labeled with Avanti Polar Lipids) were applied to 5 μg / cm ² , respectively, and allowed to stand for 4 hours. After that, the three-dimensional skin model was taken out and frozen, and was taken as a thin layered section and photographed with a confocal laser microscope (ＦＶ-1000, manufactured by Olympus). The degree of penetration of the fluorescent material into the stratum corneum was calculated by the following equation, and was determined using the four-step judgment criteria in (B) below. In addition, the degree of penetration was calculated at 10 locations and their average values were calculated. In addition, all of the vesicle compositions were prepared with an average particle diameter of about 200 nm using a mini-extruder (manufactured by Avanti Polar Lipids).

Penetration degree (%) = thickness of fluorescent cholesterol penetrated / thickness of the entire stratum corneum × 100

Figure 1 shows the results of confocal laser microscopy in the three-dimensional skin model of the vesicle composition of Example 1 of the present technology (the present invention), the tip of the white arrow indicates the lowest layer of the stratum corneum. The left side of FIG. 1 is a photograph of a thin layered slice, and the white portion of the right side photo is a photograph showing fluorescent cholesterol that has penetrated the thin layered slice in the same region as the left side photograph.

Figure 2 shows the results of confocal laser microscopy in the three-dimensional skin model of the vesicle composition of Comparative Example 1, the tip of the white arrow indicates the lowest layer of the stratum corneum. The left side of Fig. 2 is a photograph of the thin section, and the white part of the photo on the right is a photograph showing fluorescent cholesterol that has penetrated the thin section in the same region as the photo on the left.

As can be seen from Figures 1 and 2, the vesicle composition of the present technology (the present invention) was superior in penetration of fluorescent cholesterol in the entire stratum corneum compared to the comparative example.

In addition, the vesicle composition of the present technology is also excellent in thermal stability, and even when there is a heating step in the production of the products of Examples 13 to 16 (specifically, a cosmetic or an external preparation for skin), the vesicle composition of the present technology in the obtained product The function of can be exhibited satisfactorily.

(B) Level 4 judgment criteria

(Judgment): (Evaluation)

◎: Penetration degree is over 50%

○: Penetration degree is more than 40% but less than 50%

△: Penetration degree is more than 30% but less than 40%

×: Penetration degree is less than 30%

[Skin affinity]

For each sample, 20 panelists specialized in cosmetic evaluation evaluated the skin affinity felt when applied to the inner side of the upper arm, and the panel was evaluated in 6 steps according to the following absolute evaluation, and the panel was rated for each sample. The average value was calculated from the total and judged according to the following four-step judgment criteria.

Absolute evaluation criteria

(Rating): (Evaluation)

6 points: Strong skin affinity

5 points: Feel the skin affinity

4 points: Feels a little skin affinity

3 points: Moderate

2 points | pieces: It does not feel much skin affinity

1 point: Does not feel skin affinity

4th Step Criteria

(Judgment): (Average point of rating)

◎: 5 points or more

○: 3.5 points or more and 5 points or less

△: More than 2 points and less than 3.5 points

×: 2 or less points

As is clear from the results of Tables 1 and 2, the vesicle compositions of Examples 1 to 11 of the present technology (the present invention) were excellent in both stability over time, skin permeability, and skin affinity. On the other hand, Comparative Example 1 in which neither N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate nor polylysine was contained was insufficient in skin permeability and skin affinity. In Comparative Example 2, which did not contain the N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate, in particular, the aging stability of the vesicle was poor, so that aggregation occurred, and a satisfactory point in terms of skin affinity was not obtained. Comparative Example 3 without polylysine was not particularly satisfactory in terms of skin permeability.

Example 12: Vesicle composition

(ingredient) (%)

1. Hydrogenated soybean phospholipid (Note 1) 1.0

2. Cholesterol (Note 2) 0.25

3. Glyyrrhetinic acid stearyl (Note 8) 0.1

4. Dipropylene glycol 10.0

5. Purified water 30.0

6. Polylysine 10% aqueous solution (Note 6) 0.5

7. Citric Acid 0.11

8. N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate (Note 7) 0.1

9. Residual water

Note 8: Ciogretinol (manufactured by Maruzen Pharmaceuticals)

(Manufacturing method)

A: Components 1 to 4 were heated to 80 ° C to obtain a solution.

Components 5 to 7 and components 8 to 9 were respectively added to the solution obtained in B: A while maintaining at 75 ° C, and a dispersion was obtained by a disper mixer.

The dispersion obtained in C: B was gradually cooled to 40 ° C to obtain a vesicle composition.

The vesicle composition of Example 12 was excellent in both stability over time, skin permeability, and skin affinity.

Example 13: Beauty liquid

(ingredient) (%)

1. Isostearyl alcohol 0.5

2. Hydrogenated soybean phospholipid (Note 1) 1.5

3. Glyceryl monostearate 0.5

4. Cetyl isooctanoate 5.0

5. Behenyl alcohol 0.5

6. Glycerin 12.0

7. 1,3-butylene glycol 8.0

8. Residual water

9. Xanthan gum 0.1

10. Hydroxypropyl methylcellulose (Note 9) 0.1

11. Vesicle composition 20.0 described in Example 12

12. Phenoxy Ethanol 0.3

13. Flavor 0.2

(Note 9) METLOSEE 65SＨ4000 (Shin-etsu chemical co., Ltd. Product)

(Manufacturing method)

A: Components 1 to 5 are dissolved at 70 ° C and mixed uniformly.

B: Components 6-10 are uniformly mixed at 70 ° C.

C: B is added to A to emulsify at 70 ° C.

D: C was cooled to 40 ° C, components 11 to 13 were added, and uniformly mixed to obtain a cosmetic liquid.

The cosmetic liquid of Example 13 was a cosmetic liquid having excellent skin permeability and stability over time of the vesicle, and excellent skin affinity and moisturizing effect.

Example 14: Water-type eye cream

(ingredient) (%)

1.Glyceryl monostearate 3.5

2. Monostearic acid polyethylene glycol (40 mol) 2.0

3. Liquid paraffin 3.0

4. Vaseline 8.0

5. Tri 2-ethylhexanoate glyceryl 5.0

6. Dimethyl Polysiloxane 1.0

7. Cetostearyl alcohol 2.0

8. Behenyl Alcohol 2.0

9. 1,3 Butylene glycol 5.0

10. Xanthan gum 0.1

11. Refining water balance

12. Sodium Edetate 0.05

13. Methyl paraoxybenzoate 0.1

14. Vesicle composition 5.0 as described in Example 1

15. Fragrance 0.1

(Manufacturing method)

A: Components 1 to 8 are dissolved by heating to 70 ° C.

B: Components 9 to 13 were dissolved by heating to 70 ° C, and then added to A to emulsify.

After cooling C: B to room temperature, components 14-15 were added to obtain an oil-in-water eye cream.

The oil-in-water type eye cream of Example 14 was an oil-in-water type eye cream having excellent skin permeability and stability over time of the vesicle, and excellent skin affinity and moisturizing effect.

Example 15: Cosmetic water

(ingredient) (%)

1. Glycerin 5.0

2. 1,3-butylene glycol 5.0

3. Succinic acid 0.07

4. Sodium succinate 0.07

5. Mono oleic acid

     Polyoxyethylene (20 mol) sorbitan 1.2

6. Ethanol 8.0

7. Methyl paraoxybenzoate 0.1

8. Flavoring 0.05

9. Vesicle composition of Example 2 5.0

10. Residual water

11.kojic acid 0.5

(Manufacturing method)

A: Components 5 to 8 are mixed and dissolved.

B: Components 1-4 and 10-11 are mixed and dissolved.

A was added to C: B and mixed, and component 9 was further added and mixed to obtain a lotion.

The lotion of Example 15 was excellent in skin permeability and stability over time of the vesicle, and was excellent in skin affinity and moisturizing effect.

Example 16: Oil-in-water emulsion (水中 油 型 乳液)

(ingredient) (%)

1.Squalane 5.0

2. Decamethyl cyclopentasiloxane 5.0

3. Polyoxyethylene (60) hardened castor oil 2.0

4. Cetostearyl alcohol 0.5

5. 1,3-butylene glycol 7.0

6. Glycerin 5.0

7. Acrylic acid-methacrylate alkyl copolymer (Note 10) 0.2

8. methyl paraoxybenzoate 0.05

9. Triethanolamine 0.2

10. Sodium edetate 0.02

11. Refining water balance

12. Flavoring 0.02

13. Vesicle composition 10.0 of Example 6

14. Dipropylene glycol 7.0

15. Purified water 10.0

Note 10: Pemulen TR-2 (manufactured by NOVEON)

(Manufacturing method)

A: Components 1 to 6 are dissolved by heating at 70 ° C.

B: Components 7-11 are heated at 70 ° C, then added to A to emulsify.

C: B is cooled to room temperature.

Components 12 to 15 were added to D: C to obtain an oil-in-water emulsion.

The oil-in-water emulsion of Example 16 was excellent in skin permeability and stability over time of the vesicle, and was excellent in skin affinity and moisturizing effect.

Claims (11)

The following components (A) to (D);
(A) 0.01 to 5% by mass of phospholipids
(B) One or two or more selected from cholesterol and phytosterol 0.01 to 5% by mass
(C) One or two kinds selected from quaternary ammonium salts and mono-N-long chain acyl basic amino acid 低級 alkylester 鹽 0.001 to 1.0% by mass
(D) Polypeptide 0.001 to 5.0% by mass of a polypeptide having a ratio of basic amino acids of 90% mol or more in the polypeptide.
Vesicle composition containing (vesicle 組成 物).
According to claim 1,
A vesicle composition having a number average molecular weight of the component (D) of 1500-10000.
According to claim 1,
The basic composition of the component (D), arginine (arginine), lysine (lysine) and histidine (histidine) selected from one or two or more vesicle composition.
According to claim 1,
The above component (C) is dipalmitoyl ethylhydroxy ethylmoniummethosulfate or N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate (N-cocoyl-L-arginin ethylester pyrrolidone carboxylate) Phosphoric vesicle composition.
According to claim 1,
A vesicle composition wherein the component (D) is polylysine.
According to claim 1,
The component (D): component (C) contains a mass ratio of 1: 0.01 to 10 vesicle composition.
According to claim 1,
A vesicle composition having a pH at 25 ° C in the range of 3.0 to 6.5.
According to claim 1,
Vesicle composition having a ζ potential of 5 to 100 at 25 ° C.
An external preparation for skin comprising the vesicle composition of any one of claims 1 to 8.
A cosmetic comprising the vesicle composition according to any one of claims 1 to 8.
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