HK1207986B - Vesicle composition, and external preparation for skin and cosmetic preparation each of which contains same - Google Patents

Description

Vesicle composition, and external preparation for skin and cosmetic containing the same

Technical Field

The present invention relates to a vesicle composition comprising a phospholipid as a component (a), 1 or 2 or more kinds of components (B) selected from cholesterol and phytosterol, a cationic surfactant as a component (C), and a polypeptide mainly composed of a basic amino acid as a component (D), and an external preparation for skin and a cosmetic containing the vesicle composition.

Background

Conventionally, as a method for blending a water-insoluble active ingredient in a skin external preparation or a cosmetic, a method of dispersing a water-insoluble active ingredient in the form of vesicle particles in an aqueous solvent has been widely used.

Generally, vesicles are produced by dispersing a vesicle main component and an active ingredient in an aqueous solvent, and then subjecting the resulting dispersion to ultrasonic treatment and high-pressure treatment. In addition, the vesicle main component is composed of a surfactant, and the long-term stability of the vesicle itself depends on the intermolecular force of the surfactant. Therefore, since the vesicles are susceptible to aggregation or the like due to the external environment, and thus have poor long-term stability, development of vesicles having excellent long-term stability has been desired.

As amphiphiles constituting vesicles for improving the long-term stability of the vesicles, phospholipid derivatives are known, for example, which are prepared from naturally-derived phospholipids as a raw material and have an acyl group at the 2-position as a residue of an unsaturated fatty acid (see, for example, patent document 1).

In addition, as techniques for improving the long-term stability of vesicles, there are known: a vesicle for cosmetics prepared by using hydrogenated soybean phospholipid having a phosphatidylcholine content of 90 wt% or more and an iodine value of 0.1 or less and adjusting the average particle diameter to 100 to 500nm (see, for example, patent document 2); further, a vesicle composition comprising 1 or 2 or more kinds of vesicle-forming substances selected from the group consisting of phospholipids, sucrose fatty acid esters and metal acylamino acids and a water-soluble polymer, which is obtained by allowing the water-soluble polymer to exist and subjecting the resultant to a high-pressure treatment at the time of vesicle formation (for example, see patent document 3), and the like.

On the other hand, active ingredients also have low skin permeability, and a technique capable of efficiently permeating the active ingredients into the skin is also desired. For example, there are the following techniques: the substance or mixture thereof for promoting intracellular penetration of the above effective components is prepared from phospholipid liposome, and is prepared by quaternizing to obtain compound of formula R-N (R)₁R₂R₃) Type (wherein R is a symbol of a plant protein molecule, R is₁And R₂Independently is a C1-C6 hydrocarbyl group, R₃An alkyl group having 10 to 18 carbon atoms) to enhance intracellular permeation (see, for example, patent document 4).

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open No. 2008-88133

Patent document 2: japanese patent laid-open publication No. 2006-124378

Patent document 3: japanese laid-open patent publication No. 2008-94808

Patent document 4: japanese patent No. 4950419

Disclosure of Invention

Problems to be solved by the invention

The present invention provides a vesicle composition having excellent long-term stability and skin permeability and further having excellent skin-friendly feeling when used, and an external preparation for skin and a cosmetic containing the same.

Means for solving the problems

As a result of intensive studies, the present inventors have found that the long-term stability is insufficient when only the specific phospholipid described in patent document 2 is used, and that the method of adding a water-soluble polymer to the vesicle in production of the vesicle described in patent document 3 may be restricted in terms of the feel of the water-soluble polymer due to the feeling of touch. Further, the method of patent document 4, which contains a plant protein quaternized with an amine compound, has a problem of long-term stability such as discoloration due to odor.

The present inventors have made intensive studies in view of such circumstances, and as a result, have found that by combining a phospholipid and 1 or 2 or more kinds of phospholipids selected from cholesterol and phytosterol with a polypeptide mainly composed of a basic amino acid, the polypeptide promotes the adsorption of the vesicles in the stratum corneum, and the vesicles containing the phospholipid and 1 or 2 or more kinds of phospholipids selected from cholesterol and phytosterol effectively permeate into the skin, and the skin-friendly feeling when used is improved.

However, when vesicles formed of a phospholipid and 1 or 2 or more kinds selected from cholesterol and phytosterol are combined with a polypeptide mainly composed of a basic amino acid, problems such as poor long-term stability and aggregation due to the poor long-term stability occur in cosmetics, skin preparations for external use, and the like.

The present inventors have further studied and found that a cationic surfactant is used in combination with a phospholipid, 1 or 2 or more members selected from cholesterol and phytosterol, and a polypeptide mainly composed of a basic amino acid, whereby the cationic surfactant can improve the dispersibility of vesicles formed from the polypeptide and 1 or 2 or more members selected from cholesterol and phytosterol, and the phospholipid, and can improve the skin permeability of the vesicles and the skin-friendly feeling during use, and have completed the present invention.

That is, the present invention provides a vesicle composition comprising the following components (a) to (D):

(A) phosphatide,

(B) 1 or more than 2 selected from cholesterol and phytosterol,

(C) A cationic surfactant,

(D) A polypeptide mainly comprising a basic amino acid.

The present invention also provides the vesicle composition, wherein the component (C) is a cationic surfactant having an amino acid residue.

The present invention also provides the vesicle composition, wherein the component (C) is a lower alkyl ester salt of a mono-N-long chain acyl basic amino acid.

The present invention also provides the vesicle composition, wherein the number average molecular weight of the component (D) is 1500 to 10000.

The present invention also provides the vesicle composition, wherein the basic amino acid of the component (D) is 1 or 2 or more selected from arginine, lysine and histidine.

The present invention also provides the vesicle composition, wherein the proportion of the basic amino acid in the component (D) is 60 mol% or more.

The present invention also provides the vesicle composition, wherein the component (C) is N-cocoyl-L-arginine ethyl pyrrolidone carboxylate.

The present invention also provides the vesicle composition, wherein the component (D) is polylysine.

The present invention also provides the vesicle composition, wherein the pH at 25 ℃ is in the range of 3.0 to 6.5.

The present invention also provides the vesicle composition, which has a zeta potential at 25 ℃ of 5 to 100.

In addition, provided are an external preparation for skin and a cosmetic, which contain the above vesicle composition.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, a combination of a phospholipid, 1 or 2 or more selected from cholesterol and phytosterol, a cationic surfactant, and a polypeptide mainly composed of a basic amino acid can provide a vesicle composition having excellent long-term stability and skin permeability and further having excellent skin-friendly feeling in use, and a skin external agent and a cosmetic containing the vesicle composition.

Drawings

FIG. 1 is a photograph showing confocal laser microscope observations of a three-dimensional skin model of the vesicle composition of the present technology.

FIG. 2 is a photograph showing confocal laser microscope observation results of a three-dimensional skin model of the vesicle composition of the comparative example instead of using a photograph.

Detailed Description

The present technology relates to a vesicle composition comprising a phospholipid as a component (A), 1 or 2 or more kinds selected from cholesterol and phytosterol as a component (B), a cationic surfactant as a component (C), and a polypeptide mainly composed of a basic amino acid as a component (D), and to a skin external preparation and a cosmetic containing the vesicle composition.

The present technology (present invention) is explained in detail below. In the present specification, "to" means a range including numerical values before and after the range.

The phospholipid of the component (a) usable in the present technology is a phospholipid usable as a vesicle-constituting component in the present technology, and is not particularly limited as long as it can be used in general cosmetics, skin external preparations, and the like. Preferred specific examples include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, sphingomyelin, and the like, and 1 or 2 or more selected from them.

Further, the component (a) may be a composition containing 1 or 2 or more kinds of the above-mentioned phospholipids. Examples of the phospholipid-containing composition include soybean lecithin (also referred to as "soybean phospholipid"), egg yolk lecithin (also referred to as "egg yolk phospholipid"), hydrogenated products thereof, and lysolecithins obtained by enzymatically treating and lysolyzing the above-mentioned materials. Among them, hydrogenated phospholipids are preferable, and hydrogenated soybean phospholipids are more preferable.

Among them, 1 or 2 or more kinds of them can be used in combination as needed.

Specific examples of the commercial products include HSL-70 supplied by YMC Co., Ltd., Nikko Chemicals Co., Ltd., Nikkol Lecinol S-10E supplied by Nikkon OilliO Group, Ltd., Basis LS-60HR supplied by Nisshin OilliO Group, Ltd., yolk lysolecithin LPC-1 supplied by Kewpie Corporation, and the like.

The content of the component (a) in the present technology is not particularly limited, but is preferably 0.01 to 5% by mass in the vesicle composition from the viewpoint of long-term stability and skin-friendly feeling, more preferably 0.05 to 4% by mass, and even more preferably 0.1 to 2% by mass from the viewpoint of long-term stability.

The 1 or 2 or more selected from the group consisting of cholesterol and phytosterol as the component (B) usable in the present technology contributes to the stability of the bilayer membrane structure in vesicle formation, and can improve the long-term stability by containing it. Cholesterol and phytosterols may also be used in combination.

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

The phytosterol may be any substance generally classified as a phytosterol (plant sterol), and examples of the constituent components include campesterol, sitosterol, stigmastanol, and the like. The component may be obtained by extracting germ of grain with organic solvent and removing water-soluble part, or may be purchased and used as a commercial product.

The content of the component (B) in the present technology is not particularly limited, and is preferably 0.01 to 5% by mass in the vesicle composition from the viewpoint of long-term stability and skin-friendly feel, more preferably 0.05 to 3% by mass, and still more preferably 0.05 to 1% by mass from the viewpoint of skin-friendly feel.

In addition, the ratio of the content ratios of the component (a) and the component (B) is preferably set to 1: 0.01-1: 1.

the cationic surfactant of component (C) usable in the present technology has the effect of improving the dispersibility of vesicles and further providing skin permeability and a skin-friendly feel during use.

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

Examples of the component (C) include quaternary ammonium salts such as cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, behenyltrimethylammonium chloride, behenyltrimethylammonium bromide, behenyltrimethylammonium methylsulfate, distearyldimethylammonium chloride, dioleyldimethylammonium bromide, cetylbehenyldimethylammonium methylsulfate, stearyldimethylbenzylammonium chloride, dipalmitoylethyl ammonium methylsulfate, dicocoylethyl ammonium methylsulfate, distearoylethyl hydroxyethyl ammonium methylsulfate; mono-N-long chain acyl basic amino acid lower alkyl ester salts such as stearyl lysine butyl ester hydrochloride, N-coconut oil fatty acid acyl-L-arginine ethyl ester DL-pyrrolidone carboxylate, lauroyl-ornithine propyl ester acetate, and the like; and guanidine derivatives such as decyl guanidine acetate, 2-guanylethyl lauramide hydrochloride, and 2-guanylbutyl stearamide, DL-pyrrolidone carboxylate, and 1 or 2 or more kinds of them can be selected from them. Examples of the salts thereof include halogen, methyl sulfate, ethyl sulfate, metaphosphate, and the like.

Among them, quaternary ammonium salts and mono-N-long chain acyl basic amino acid lower alkyl ester salts are preferable in the present technology. Further, among the quaternary ammonium salts, di-long chain acyl alkyl hydroxyalkyl ammonium salts (for example, dipalmitoylethyl ammonium methyl sulfate, dicocooylethyl hydroxyethyl ammonium methyl sulfate, distearoyl ethyl hydroxyethyl ammonium methyl sulfate and the like) are preferable.

The carbon number of the "long chain acyl group" in the "di-long chain acyl alkyl hydroxyalkyl ammonium salt" and the "mono-N-long chain acyl basic amino acid lower alkyl ester salt" is preferably 10 to 30, more preferably 8 to 22. The "long-chain acyl group" may be a substance derived from a plant-based mixed fatty acid (e.g., lauric oils such as coconut oil fatty acid and palm kernel oil fatty acid) or a substance derived from an animal-based mixed fatty acid (e.g., tallow oil fatty acid). Examples of the fatty acid to be the "long chain acyl group" include lauric acid, myristic acid, palmitic acid, linoleic acid, oleic acid, linolenic acid, stearic acid, and the like, and 1 or 2 or more species of these may be selected and used. In addition, in the case of "dilong chain acyl groups", they may be the same or different.

The "alkyl group", hydroxyalkyl group "and lower alkyl group" preferably have 1 to 7 carbon atoms, more preferably 1 to 5 carbon atoms, and examples of the "alkyl group" and lower alkyl group include methyl group, ethyl group, propyl group and butyl group.

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

Further, among the above cationic surfactants, those having an amino acid residue are also preferable. The surfactant used in the present technology may be any surfactant that has 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. The cationic surfactant having an amino acid residue is preferably a surfactant having an L-arginine residue (also referred to as "L-arginine-based surfactant"). In the case of an L-arginine-based surfactant, the surfactant may be any amphoteric surfactant as long as it is cationic in the vesicle composition.

Further, among the cationic surfactants having an amino acid residue in the present technology, examples of the L-arginine-based surfactant include: as アミセーフLMA-60 (trademark, Ajinomoto Co., manufactured by Inc.) commercially available N- [ 3-alkyl (C)₁₂And C₁₄) Oxo-2-hydroxypropanol]A 2% aqueous solution of L-arginine hydrochloride, and N-cocoyl-L-arginine ethyl pyrrolidone carboxylate which has been sold as CAE (trademark, Ajinomoto co., inc.) and is preferably N-cocoyl-L-arginine ethyl pyrrolidone carboxylate. When 1 or 2 or more selected from them are used, not only the long-term stability is improved, but also a vesicle composition having excellent skin permeability is obtained, and therefore, it is preferable.

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

The polypeptide mainly composed of a basic amino acid of the component (D) usable in the present technology has an effect of improving both the skin permeability of vesicles and the skin feel during use. Basic amino acids are, for example, arginine, lysine, histidine, ornithine and the like (usually, L-form is used), and when 1 or 2 or more kinds of polypeptides selected from basic amino acids are used as the main component, it is preferable because it is a vesicle composition having excellent skin-friendly feeling. The polypeptide mainly containing a basic amino acid means that the proportion of the basic amino acid in the polypeptide is 60 mol% or more, preferably 70 mol% or more, more preferably 80 mol% or more, and still more preferably 90 mol% or more.

The number average molecular weight of the polypeptide of the component (D) varies depending on the amino acid, and is preferably 1500 to 10000. The number average molecular weight of the polypeptide of component (D) can be calculated from a High Performance Liquid Chromatography (HPLC) chart.

Further, among the polypeptides composed mainly of basic amino acids, polylysine, polyhistidine, and the like are preferable. When 1 or 2 or more selected from them are used, a vesicle composition excellent in skin permeability and skin-friendly feeling upon use is obtained, and therefore, it is preferable.

As a commercially available product of the polypeptide, polylysine 10 (a 10% polylysine-containing aqueous solution (ICHIMARU PHARCOS Co., Ltd.)) expressed by the INCI name (International Nominaturechemical aggregating labeling peptides) as Polyepsilon-Lysine, and the like can be used.

The content of the component (D) in the present technology is not particularly limited, but is preferably 0.001 to 5.0% by mass in the vesicle composition from the viewpoint of skin permeability and long-term stability, more preferably 0.005 to 1.0% by mass, and even more preferably 0.025 to 0.1% by mass from the viewpoint of long-term stability.

The vesicle composition of the present technology contains water in addition to the above-mentioned components (A) to (D). Water can be used as a dispersion medium for the above components, and is an essential component of the vesicle composition. The content of water in the present technology is appropriately determined by those skilled in the art according to the content of the components (a) to (D), and is preferably approximately 60 to 95% by mass in the vesicle composition. As such water, steam distilled water derived from plants such as purified water, hot spring water, rose water, lavender water, or the like can be used. Among them, 1 or 2 or more species can be used.

In addition, in the process of forming vesicles, it is necessary to maintain the dispersibility of the components (a) to (D) (particularly, the components (a) and (B)) well, and for the purpose of improving the dispersibility of each component, a polyhydric alcohol such as propylene glycol, 1, 3-butanediol, dipropylene glycol, 1, 2-pentanediol, glycerin, diglycerin, or sorbitol may be added to the medium. The content of the polyol in the present technology in the vesicle composition is preferably 1 to 20% by mass.

In addition, various drugs such as alcohols, oils, surfactants, thickeners, powders, chelating agents, pH adjusting agents, ultraviolet absorbers, extracts derived from plants and microorganisms, moisturizers, anti-inflammatory agents, cell activators, and perfumes may be added to the vesicle composition of the present technology within the range that does not impair the effects of the present technology. The various additives may be added during or after the production of the vesicles. Alternatively, it may or may not be encapsulated in vesicles.

Further, the vesicle composition of the present technology is preferable because it has high zeta potential, and therefore, it has high long-term stability and high skin permeability. The zeta potential is not particularly limited, but is preferably 5 to 100 (more preferably 7 or more and 80 or less, and still more preferably 10 or more and 50 or less) because long-term stability is more excellent. The zeta potential is a value measured at a temperature of 25 ℃ using an electrophoretic light scattering photometer LEZ-600 manufactured by Otsuka Electronics co.

The pH of the vesicle composition of the present technology is not particularly limited, and since the zeta potential is increased to improve the long-term stability and skin permeability, the pH at 25 ℃ is preferably in the range of 3.0 to 6.5 (preferably 3.5 to 5.0).

The method for producing the vesicle composition of the present technology is not particularly limited, and can be produced by a usual method. For example, it can be produced by the following method: vortex method [ A.D.Bangham, J.mol.biol.,13,238(1965)]Sonication [ 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 [ Y.Barenholz, FEBSLett.,99,210(1979)]Cholic acid removal method [ Y.Kagawa, J.biol.chem.,246,5477(1971)]TritonX-100 batch method [ W.J.Gerritsen, Eur.J.biochem.,85,255(1978)]、Ca²⁺Fusion method [ D.Papapapapadojoulos, biochem. biophysis. acta.,394,483(1975)]Ether injection method [ D.Deazer, biochem.Biophys.acta.,443,629(1976)]Heat treatment (annealing) [ R.Lawaczeck, biochem.Biophys.acta.,443,313(1976)]Freeze-thaw 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))]Polyol process [ Japanese unexamined patent publication No. Sho 60-7932 ]]And the like.

Examples of the method for producing the vesicle composition of the present technology include the following methods: the vesicle composition can be obtained by using the above-mentioned component (a) and the above-mentioned component (B) as the main film-constituting components of the vesicle particles, blending these components (a) and (B), the component (C) and the component (D), and other optional components as appropriate, heating and mixing them, and then cooling them. The temperature condition for heating and mixing is preferably 60 to 100 ℃.

Further, [ component (a) + component (B) ]: the content ratio of the component (C) is preferably 1: 0.001 to 1, more preferably 1: 0.01 to 0.4.

Further, [ component (a) + component (B) ]: the content ratio of the component (D) is preferably 1: 0.001 to 1, more preferably 1: 0.01 to 0.8, preferably 0.02 to 0.08.

Further, component (D): the content ratio of the component (C) is preferably 1: 0.01 to 10, more preferably 0.1 to 5, and still more preferably 1: 1 to 4.

As an example thereof, the compound (a) and the compound (B) are dispersed and dissolved in an aqueous solvent such as purified water or polyhydric alcohol at 80 ℃, a substance obtained by adding the compound (C) to purified water and dissolving the compound by heating at 80 ℃ is added thereto and mixed, a substance obtained by adding the compound (D) to purified water and dissolving the compound by heating at 80 ℃ is added and mixed, and then the mixture is slowly cooled to 40 ℃.

The method for confirming blister formation may be performed by: confirming the existence of a Maltese cross image under the crossed Nicol prism by using a polarized light microscope; peaks and the like measured by a small-angle X-ray scattering spectrum were confirmed using a high-brightness small-angle X-ray scattering apparatus SAXS (manufactured by Anton Paar). The confirmation of the vesicle formation of the vesicle composition of the present technology was performed by observing the sample under crossed nicols using a polarized light microscope (manufactured by Olympus Corporation) and confirming the presence or absence of a Maltese cross image.

There is no particular limitation on the use of the vesicle compositions of the present technology. The vesicle composition of the present technology can be used for the production of compositions for various applications such as skin external preparations (for example, skin external preparations for pharmaceuticals and quasi drugs), cosmetics, pharmaceuticals (for oral administration, injection, etc.), foods, and the like. The vesicle composition of the present technology is also excellent in heat resistance, and can exhibit the effects expected in the present technology even when it is blended at the time of production thereof. These compositions may be in any form such as liquid, semi-liquid (including gel and paste), solid, and the like.

The vesicle composition of the present technology has a characteristic of excellent skin permeability, and from this viewpoint, it is preferably used as an external preparation for skin or a cosmetic, or used in the production thereof.

The vesicle composition of the present technology can be used as it is as an external preparation for skin or a cosmetic, or can be used as an external preparation for skin or a cosmetic by adding other components thereto. When the vesicle composition of the present technology is incorporated into an external preparation for skin or a cosmetic preparation containing other ingredients, the content of the vesicle composition in these preparations is not particularly limited, but is preferably 1.0 to 90% by mass, more preferably 3.0 to 50% by mass.

An example of a method for producing an external preparation for skin or a cosmetic product using the vesicle composition of the present technology is as follows. The method for producing the vesicle composition of the present technology and the skin external preparation or cosmetic preparation comprising mixing the vesicle composition with an active ingredient or the like are included.

The pH at 25 ℃ of the produced external preparation for skin or cosmetic is not particularly limited, but it is preferable that the difference between the pH at the time of producing the vesicle composition and the pH of the finally produced external preparation for skin or cosmetic is small, and specifically, when the difference is 1.0 or less, the shape of the vesicle is maintained in the external preparation for skin or cosmetic, and the dispersibility and the long-term dispersibility can be maintained well.

The formulation of the skin external preparation or cosmetic of the present technology is not particularly limited. And may be any of liquid, semi-liquid, solid, etc. Examples thereof include: various skin external preparations or cosmetics such as lotion, cream, lotion, essence (serum), pack, cleanser, makeup cosmetics, ointment, etc. In addition, various ingredients generally used in skin external preparations or cosmetics, that is, alcohols, oils, surfactants, thickeners, powders, chelating agents, pH adjusters, ultraviolet absorbers, extracts derived from plants or microorganisms, moisturizers, anti-inflammatory agents, cell activators, and other various drugs, perfumes, and the like can be appropriately added to the skin external preparations or cosmetics of the present technology, in addition to the vesicle composition of the present technology, within a range that does not impair the effects of the present technology.

The function of the vesicles in the skin external preparation or cosmetic of the present technology is not particularly limited. It is a vesicle formed of phospholipid and has a characteristic of excellent skin permeability. In this mode, the above-described functions can be obtained, and the effect of the sustained release of the active ingredient can also be obtained.

The present technology can also adopt the following scheme.

[1] A vesicle composition comprising the following components (A) to (D):

(A) phosphatide,

(B) 1 or more than 2 selected from cholesterol and phytosterol,

(C) A cationic surfactant,

(D) A polypeptide mainly comprising a basic amino acid.

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

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

[4] The vesicle composition according to any one of the above [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 the above [1] to [4], wherein the basic amino acid of the component (D) is 1 or 2 or more selected from arginine, lysine and histidine.

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

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

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

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

[10] The vesicle composition according to any one of the above [1] to [9], which has a zeta potential at 25 ℃ of 5 to 100.

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

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

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

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

[15] The vesicle composition according to any one of the above [1] to [14], wherein [ the component (A) + the component (B) ]: the content ratio of the component (C) is 1: 0.001 to 1.

[16] The vesicle composition according to any one of the above [1] to [15], wherein [ the component (A) + the component (B) ]: the content ratio of the component (D) is 1: 0.001 to 1.

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

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

[19] The vesicle composition according to any one of the above [1] to [18], which is obtained by mixing the component (A) and the component (B) in an aqueous solvent under heating, and then mixing the aqueous solvent in which the components (C) and (D) are dissolved under heating. When the mixture is heated, a pharmacologically acceptable additive (preferably, a pharmacologically effective ingredient) is preferably added.

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

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

Examples

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 and the like.

Examples 1 to 11 and comparative examples 1 to 3: vesicle compositions

The vesicle compositions having the compositions shown in tables 1 and 2 were produced by the following production methods, and the results of the evaluation and judgment of the "long-term stability", "skin permeability" and "skin-friendly feel" of each sample by the methods shown below are shown in tables 1 and 2.

[ Table 1]

(％)

[ Table 2]

(％)

Note 1: HSL-70(YMC Co., manufactured by Ltd.)

Note 2: nissui Marine cholestrol (Nippon Suisan Kaisha, Ltd.)

Note 3: 25-NBD Chlororeterol (manufactured by Avanti Polar Lipids Co., Ltd.)

Note 4: phytosterols (Eisai Food & Chemical Co., Ltd., manufactured by Ltd.)

Note 5: DEHYQUART AU-56/G (manufactured by Cognis corporation)

Note 6: polylysine 10(ICHIMARU PHARCOS Co., Ltd., molecular weight of about 5000, manufactured by Ltd.)

And 7, note: CAE (Ajinomoto Co., manufactured by Inc.)

(production method)

A: heating the components 1-6 to 80 ℃ to form a solution.

B: while keeping at 75 ℃, components 7 to 9 and 10 to 11 were added to the solution obtained in A, respectively, and a dispersion was obtained by a dispersion mixer.

C: the dispersion from B is slowly cooled to 40 ℃ to provide the vesicle composition.

[ measurement of pH ]

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

[ zeta potential measurement ]

The zeta potential of each sample was measured at 25 ℃ using an electrophoretic light scattering photometer LEZ-600 manufactured by Otsuka Electronics co., ltd. The measurement was performed 3 times, and the results were expressed as the average value thereof.

[ confirmation test of vesicles ]

Each of the samples was observed under crossed Nicol using a polarizing microscope (manufactured by Olympus Corporation) to confirm the presence or absence of a Maltese cross image.

[ Long-term stability ]

Regarding the long-term stability, the long-term stability of the vesicles was evaluated by observing a Maltese cross image using a polarized light microscope. Specifically, the number of confirmed maltese cross images was determined by observing the state of each sample after standing at 50 ℃ for 1 month, based on the state of each sample immediately after production, and using the following (i) 4-stage criterion.

(i) 4-level judgment reference

(judgment): (evaluation)

◎ it was confirmed that the number of Maltese cross images was 80% or more

○ it was confirmed that the number of Maltese cross images was 60% or more but less than 80%

△ it was confirmed that the number of Maltese cross images was 30% or more but less than 60%

X: the number of Maltese cross images was confirmed to be less than 30%

[ skin Permeability ]

A three-dimensional skin model (TESTSKIN LSE) manufactured by Toyobo Co., Ltd. was placed on an aluminum plate in such a manner that PBS (pH7.4) was wetted to the dermis side, and the three-dimensional skin model was coated with 5. mu.g/cm in each of examples 1 to 11 and comparative examples 1 to 3, which were labeled with fluorescent cholesterol (25-NBD Chlororesterol, Avanti Polarlipids Co., Ltd.)²And left to stand for 4 hours. Then, the three-dimensional skin model was removed, frozen, and then sliced into thin sections, which were photographed by a confocal laser microscope (FV-1000, Olympus corporation). The degree of penetration of the fluorescent substance into the horny layer was calculated from the following formula, and the judgment was made using the following (ii)4 th-order judgment criterion. The degrees of penetration in 10 places were calculated, and the average value of the degrees was calculated. The vesicle composition was prepared using a micro-extruder (Avanti Polar Lipids Co., Ltd.) so that the average particle diameter was about 200 nm.

Degree of permeation (%) (% of fluorescent cholesterol permeation/thickness of whole horny layer × 100

FIG. 1 shows the confocal laser microscopy observations of a three-dimensional skin model of the vesicle composition of example 1 of the present technology (invention), the tips of the white arrows representing the lowest layer of the stratum corneum. In FIG. 1, the left side shows a photograph of a thin section, and the white portion of the right side shows fluorescent cholesterol permeating the thin section at the same position as that of the left side.

FIG. 2 shows the results of confocal laser microscope observation of a three-dimensional skin model of the vesicle composition of comparative example 1, with the tip of the white arrow representing the lowermost layer of the stratum corneum. In FIG. 2, the left side is a photograph of a thin section, and the white portion of the right side is a photograph showing fluorescent cholesterol permeating the thin section at the same position as that of the left side.

As is clear from FIGS. 1 and 2, the vesicle composition of the present technology (invention) is superior in the penetration of fluorescent cholesterol into the whole stratum corneum as compared with the comparative examples.

The vesicle composition of the present technology is also excellent in thermal stability, and even when a heating step is present in the production of the products of examples 13 to 16 (specifically, cosmetics, external preparations for skin, etc.), the function of the vesicle composition of the present technology can be exhibited well in the obtained products.

(ii) 4-level judgment reference

(judgment): (evaluation)

◎ penetration degree of more than 50%

○ the penetration degree is more than 40% and less than 50%

△ the penetration degree is more than 30% and less than 40%

X: the penetration degree is less than 30 percent

[ skin-friendly feeling ]

The skin-friendly feeling felt when applied to the inner side of the wrist was evaluated to 6 grades for each sample by the cosmetic evaluation panel 20 according to the following absolute evaluation, and the average value was calculated from the total scores of the panel for each sample and was judged by the following 4-grade judgment criteria.

Reference for absolute evaluation

(score): (evaluation)

And 6, point: fully feel skin-friendly feeling

And 5, point: feeling of skin-friendly feeling

And 4, point: slightly feel skin-friendly

And 3, point: general feeling

And 2, point: the skin-friendly feeling is not felt too much

Point 1: no skin-friendly feeling was felt

4-level judgment reference

(judgment): (average score of scores)

◎ score more than 5

○ is more than 3.5 minutes and less than 5 minutes

△ that is more than 2 points and less than 3.5 points

X: 2 min or less

As is clear from the results in tables 1 and 2, the vesicle compositions of examples 1 to 11 of the present technology (invention) are all excellent in long-term stability, skin permeability and skin-friendly feeling. In contrast, comparative example 1, which did not contain N-cocoyl-L-arginine ethyl pyrrolidone carboxylate and polylysine, was insufficient in skin penetration and skin-friendly feel. The vesicles of comparative example 2, which did not contain N-cocoyl-L-arginine ethyl pyrrolidone carboxylate, were particularly poor in long-term stability, aggregated, and not satisfactory in terms of skin-friendly feel. Comparative example 3 containing no polylysine was not satisfied particularly in terms of skin permeability.

Example 12: vesicle compositions

Note 8: STEARYL GLYCYRRHETINATE (Maruzen Pharmaceuticals Co., Ltd.)

(production method)

A: heating the components 1-4 to 80 ℃ to form a solution.

B: while keeping the temperature at 75 ℃, components 5 to 7 and 8 to 9 are added to the solution A, respectively, and a dispersion is obtained by a dispersion mixer.

C: the dispersion from B is slowly cooled to 40 ℃ to provide the vesicle composition.

The vesicle composition of example 12 was all excellent in long-term stability, skin permeability and skin-friendly feeling.

Example 13: essence liquid

(Note 9) METOLOSE 65SH4000(Shin-Etsu Chemical Co., Ltd., manufactured by Ltd.)

(production method)

A: heating the components 1-5 to 70 ℃, and uniformly dissolving and mixing.

B: the components 6-10 are mixed uniformly at 70 ℃.

C: b was added to A and emulsification was carried out at 70 ℃.

D: and cooling the C to 40 ℃, and adding the components 11-13 for uniformly mixing to obtain the essence.

The essence of example 13 is excellent in skin permeability and long-term stability of vesicles, and is excellent in skin-friendly feeling and moisturizing effect.

Example 14: oil-in-water eye cream

(production method)

A: heating the components 1-8 to 70 ℃ for heating and dissolving.

B: the components 9-13 are dissolved by heating at 70 ℃, and then added to the solution A for emulsification.

C: and cooling the B to room temperature, and adding 14-15 of the components to obtain the oil-in-water eye cream.

The oil-in-water eye cream of example 14 is excellent in skin permeability and long-term stability of vesicles, and is excellent in skin feel and moisturizing effect.

Example 15: toning lotion

(production method)

A: mixing and dissolving the components 5-8.

B: mixing and dissolving the components 1-4 and 10-11.

C: adding A into B, mixing, and further adding component 9, and mixing to obtain cosmetic water.

The lotion of example 15 was excellent in skin permeability and long-term stability of vesicles, and also excellent in skin feel and moisturizing effect.

Example 16: oil-in-water emulsion

Note 10: pemulen TR-2 (manufactured by Noveon, Inc)

(production method)

A: heating and dissolving the components 1-6 at 70 ℃.

B: heating the components 7-11 at 70 deg.C, and adding into A for emulsification.

C: and cooling the B to room temperature.

D: adding 13-16 of the components into the C to obtain an oil-in-water emulsion.

The oil-in-water emulsion of example 16 is excellent in skin permeability and long-term stability of vesicles, and is excellent in skin feel and moisturizing effect.

Claims (9)

1. A vesicle composition comprising the following components (A) to (D):

0.01 to 5 mass% of (A) a phospholipid,

0.01 to 5% by mass of (B) 1 or 2 or more selected from the group consisting of cholesterol and phytosterol,

0.001 to 1.0 mass% of (C) a cationic surfactant,

0.001 to 5.0 mass% of (D) a basic amino acid, wherein the proportion of the basic amino acid in the polypeptide is 60 mol% or more,

component (D): the content ratio of the component (C) is 1: 0.01 to 10 parts by weight of a binder,

wherein the component (C) is one or two selected from quaternary ammonium salts and mono-N-long chain acyl basic amino acid lower alkyl ester salts, the carbon number of the long chain acyl is 10-30, and the carbon number of the lower alkyl is 1-7.

2. A vesicle composition according to claim 1 wherein component (D) has a number average molecular weight of from 1500 to 10000.

3. The vesicle composition of claim 1, wherein the basic amino acid of component (D) is 1 or more selected from arginine, lysine and histidine.

4. A vesicle composition according to any one of claims 1-3 wherein ingredient (C) is dipalmitoylethyl hydroxyethylammonium methyl sulfate or N-cocoyl-L-arginine ethyl ester pyrrolidone carboxylate.

5. A vesicle composition according to any one of claims 1 to 3 wherein ingredient (D) is polylysine.

6. A vesicle composition according to any one of claims 1 to 3 having a pH at 25 ℃ in the range of from 3.0 to 6.5.

7. A vesicle composition according to any one of claims 1 to 3 having a zeta potential at 25 ℃ of from 5 to 100.

8. A skin external agent comprising a vesicle composition according to any one of claims 1 to 7.

9. A cosmetic product comprising a vesicle composition according to any one of claims 1-7.