JP2022189546A - Compositions that enhance lipid fluidization - Google Patents

Abstract

To provide compositions that promote the penetration and percutaneous absorption of an active ingredient into the skin without disrupting the lipid structure of the skin.SOLUTION: Provided are: a composition that enhances the fluidization of the lipid structure of the skin, the composition characterized by containing a lipid peptide type compound in which a peptide moiety formed by repeating at least two or more identical or different amino acids is bound to a lipid moiety consisting of an aliphatic group having 10 to 24 carbon atoms; a method for enhancing the fluidization of the lipid structure of the skin; and use of an agent for skin application consisting of the composition for enhancing the fluidization of the lipid structure of the skin.SELECTED DRAWING: None

Description

The present invention relates to compositions that enhance the fluidization of skin lipids, in particular compositions containing lipid peptides.

The stratum corneum, which is the outermost tissue of the skin, prevents water evaporation, retains essential water in the body, and plays a major role in the barrier function of the skin to prevent harmful substances from entering from outside the body. Among them, intercellular lipids mainly composed of ceramide, cholesterol and fatty acids are considered to play an important role in the barrier function. The intercellular lipids form a multi-layered structure called a lamellar structure, and methods for confirming the state (structural) change include X-ray diffraction, infrared absorption, Raman spectroscopy, electron spin resonance, and differential scanning calorimetry. Measurement and the like are known (Non-Patent Document 3 and Patent Document 1).

Since this barrier function is a major obstacle to permeation of physiologically useful ingredients through the skin, research to overcome this obstacle is still being vigorously conducted (Non-Patent Document 1 and Non-Patent Documents 2).
In Non-Patent Documents 1 and 2, the penetration enhancer of the active ingredient (physiologically useful ingredient) influences the structure of the intercellular lipid by various mechanisms, thereby promoting the penetration of the ingredient. It has been reported. On the other hand, it is widely known that the collapse of the intercellular lipid structure leads to undesirable deterioration of the barrier function (for example, Patent Document 2). There is a need for an enhancer that can enhance the penetration of the skin.

Lipid peptides are known to take the form of fibers and the like and self-assemble in water or mixed aqueous solutions (Patent Document 2, Non-Patent Documents 4 and 5). Furthermore, there is a report that when a useful component (eg, ivermectin) is contained in the gel formed by the self-assembled structure, its penetration is promoted (Non-Patent Document 6).

JP 2010-237098 A Japanese Patent No. 5727932

Adv. Drug Delivery Rev. 2004, 56, 603-618. Int. J. Pharm. 2013, 447, 12-21. Int. J. Pharm., 1995, 125, 265-282. Phys. Chem. Chem. Phys. 2015, 17, 26724-26730. Phys. Chem. Chem. Phys. 2015, 17, 2192-2198. Chem. Pharm. Bull. 2018, 66, 327-333.

As described above, lipid peptides take the form of fibers or the like in water or a mixed aqueous solution and self-assemble. , reported that the permeation of the active ingredient into the skin was promoted. However, until now, sufficient studies have not been conducted on how the self-assembled structure of lipid peptides affects the skin penetration promotion mechanism of active ingredients.

An object of the present invention is to provide a composition that promotes penetration and percutaneous absorption of an active ingredient into the skin without disrupting the lipid structure of the skin.

The present inventors discovered that a composition containing at least one lipid peptide-type compound penetrates into the skin while the compound forms a self-assembled structure, thereby disrupting the lipid structure of the skin. The present inventors have found that it enhances the fluidization of the lipid structure of the skin and promotes the penetration and percutaneous absorption of active ingredients into the skin, thereby completing the present invention.

（式中、Ｒ^１は炭素原子数９乃至２３の脂肪族基を表し、Ｒ^２は水素原子、又は炭素原子数１若しくは２の分岐鎖を有し得る炭素原子数１乃至４のアルキル基を表し、Ｒ^３は－（ＣＨ_２）_ｎ－Ｘ基を表し、ｎは１乃至４の数を表し、Ｘはアミノ基、グアニジノ基、－ＣＯＮＨ_２基、又は窒素原子を１乃至３個有し得る５員環基若しくは６員環基又は５員環と６員環から構成される縮合複素環基を表す。）

（式中、Ｒ^４は炭素原子数９乃至２３の脂肪族基を表し、Ｒ^５乃至Ｒ^７はそれぞれ独立して水素原子、炭素原子数１若しくは２の分岐鎖を有し得る炭素原子数１乃至４のアルキル基、又は－（ＣＨ_２）_ｎ－Ｘ基を表し、ｎは１乃至４の数を表し、Ｘはアミノ基、グアニジノ基、－ＣＯＮＨ_２基、又は窒素原子を１乃至３個有し得る５員環基若しくは６員環基又は５員環と６員環から構成される縮合複素環基を表す。）

（式中、Ｒ^８は炭素原子数９乃至２３の脂肪族基を表し、Ｒ^９乃至Ｒ^１２はそれぞれ独立して水素原子、炭素原子数１若しくは２の分岐鎖を有し得る炭素原子数１乃至４のアルキル基、又は－（ＣＨ_２）_ｎ－Ｘ基を表し、ｎは１乃至４の数を表し、Ｘはアミノ基、グアニジノ基、－ＣＯＮＨ_２基、又は窒素原子を１乃至３個有し得る５員環基若しくは６員環基又は５員環と６員環から構成される縮合複素環基を表す。）
第４観点として、前記組成物が、前記脂質ペプチド化合物が自己組織化構造を形成した状態で皮膚内部へ浸透することを特徴とする、第１観点乃至第３観点のうちいずれか一項に記載の組成物。
第５観点として、皮膚の脂質構造の流動化を高める方法であって、
炭素原子数１０乃至２４の脂肪族基からなる脂質部に、少なくとも２つ以上の同一の又は異なるアミノ酸の繰り返しにより形成されたペプチド部が結合された脂質ペプチド型化合物を含有する組成物を皮膚に適用することを特徴とする、方法に関する。
第６観点として、前記脂質ペプチド型化合物が、上記式（１）乃至式（３）で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなることを特徴とする、第５観点に記載の方法に関する。
第７観点として、前記組成物が、前記脂質ペプチド化合物が自己組織化構造を形成した状態で皮膚内部へ浸透することを特徴とする、第５観点又は第６観点に記載の方法に関する。
第８観点として、皮膚の脂質構造の流動化を高めるための皮膚塗布剤の使用であって、該皮膚塗布剤は炭素原子数１０乃至２４の脂肪族基からなる脂質部に、少なくとも２つ以上の同一の又は異なるアミノ酸の繰り返しにより形成されたペプチド部が結合された脂質ペプチド型化合物を含有する組成物からなる、使用に関する。
第９観点として、前記脂質ペプチド型化合物が、上記式（１）乃至式（３）で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなることを特徴とする、第８観点に記載の使用に関する。
第１０観点として、前記組成物が、前記脂質ペプチド化合物が自己組織化構造を形成した状態で皮膚内部へ浸透することを特徴とする、第８観点又は第９観点に記載の使用に関する。 That is, the present invention provides, as a first aspect, a composition that enhances the fluidization of the lipid structure of the skin, wherein the lipid portion comprising an aliphatic group having 10 to 24 carbon atoms contains at least two identical or different The present invention relates to a composition comprising a lipid peptide type compound to which a peptide portion formed by repeating amino acids is attached.
As a second aspect, it relates to the composition according to the first aspect, wherein the composition is a composition that promotes fluidization of the multi-layer structure of intercellular lipids.
As a third aspect, the lipid peptide compound is composed of at least one compound represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof. It relates to a composition according to the first aspect or the second aspect.

(In the formula, R ¹ represents an aliphatic group having 9 to 23 carbon atoms, R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain of 1 or 2 carbon atoms. wherein R ³ represents a —(CH ₂ ) _n —X group, n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or has 1 to 3 nitrogen atoms; represents the 5-membered ring group or 6-membered ring group obtained, or the condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁴ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁵ to R ⁷ each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁸ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁹ to R ¹² each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom. an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)
As a fourth aspect, the composition according to any one of the first to third aspects, wherein the composition permeates into the skin in a state in which the lipid peptide compound forms a self-assembled structure. composition.
As a fifth aspect, a method for enhancing fluidization of the lipid structure of the skin, comprising:
A composition containing a lipid-peptide compound in which a peptide portion formed by repeating at least two identical or different amino acids is bonded to a lipid portion consisting of an aliphatic group having 10 to 24 carbon atoms is applied to the skin. It relates to a method, characterized in that applying
As a sixth aspect, the lipid peptide compound is composed of at least one of the compounds represented by the above formulas (1) to (3) or a pharmaceutically usable salt thereof. 5 relates to the method according to the aspect.
As a seventh aspect, it relates to the method according to the fifth or sixth aspect, wherein the composition permeates into the skin while the lipid peptide compound forms a self-assembled structure.
An eighth aspect is the use of a skin coating agent for enhancing the fluidization of the lipid structure of the skin, wherein the lipid portion comprising an aliphatic group having 10 to 24 carbon atoms contains at least two composition comprising a lipid peptide-type compound to which is attached a peptide portion formed by repeating the same or different amino acids of
As a ninth aspect, the lipid peptide compound is composed of at least one of the compounds represented by the above formulas (1) to (3) or a pharmaceutically usable salt thereof, It relates to the use according to aspect 8.
A tenth aspect relates to the use according to the eighth aspect or the ninth aspect, wherein the composition permeates into the skin while the lipid peptide compound forms a self-assembled structure.

According to the present invention, a composition containing a specific lipid peptide-type compound penetrates into the skin, preferably in a state in which the lipid peptide compound forms a self-assembled structure, thereby increasing intercellular lipid flow in the skin. Further, when the gel formed by the self-organizing structure contains useful ingredients, penetration and percutaneous absorption of the active ingredients into the skin can be promoted.
Furthermore, the composition containing the specific lipid peptide-type compound of the present invention enhances lipid fluidization without disrupting the lipid structure of the skin, thereby promoting penetration and percutaneous absorption of active ingredients. Undesirable deterioration of the barrier function caused by the collapse of the interlipid multilayer structure can be prevented.
In addition, the lipid peptide-type compound used in the composition of the present invention is an artificial low-molecular-weight compound composed only of a lipid and a peptide and having a very high safety. Therefore, the material of the present invention has high biosafety and is very useful in the above applications from the viewpoint of high safety required for pharmaceutical and cosmetic applications.

FIG. 1 shows the penetration test results of ascorbic acid 2-glucoside (AA2G) using a human three-dimensional cultured skin model, after adding the sample, A after 1 hour, B after 3 hours, and C after 6 hours. FIG. 3 is a diagram showing the permeation amount of AA2G [μg/cm ² ] after the passage of time. Figure 2 shows the permeation test time: AA2G permeation amount [μg /cm ² ] (horizontal axis) and the permeation amount of Pal-GH [μg/cm ² ] (vertical axis). FIG. 3 shows the results of microscopic observation after labeling with an aqueous solution of Thioflavin T after the skin permeation test, A and B are control examples (without Pal-GH), C and D are Example 3 (Pal-GH pre-prepared). (A and C are bright-field images, B and D are fluorescence images). In FIG. 4, A is the scattering ^intensity [a. u. ] (vertical axis) (lower spectrum: Example 3 (Pal-GH-containing sample), upper spectrum: Control example), B is 1082 cm ⁻¹ and 1061 cm in each sample (control example, Example 3) The intensity ratio of the Raman peak of ⁻¹ [I ₁₀₈₂ /I ₁₀₆₁ ] is shown. FIG. 5 shows the measurement results of SAXS, A is a control example, B is a scattering spectrum in Example 3 (aqueous solution containing 0.5% Pal-GH) (test time 15 minutes, 30 minutes, 60 minutes from the bottom of the graph, 120 minutes, 180 minutes). In addition, C is the q [Å] (left vertical axis) in the peak derived from the lipid structure (see arrows in A and B) for the test time [minute] (horizontal axis), and the interdomain distance [Å] (right vertical axis ).

The present invention relates to a composition that enhances fluidization of the lipid structure of the skin. Preferably, it relates to a composition that promotes fluidization of multi-layered structures of intercellular lipids. In the present invention, fluidization of the lipid structure means that the composition changes the alkyl chain of the lipid from the trans form to the gauche form, for example.
According to the present invention, a composition containing a specific lipid peptide compound penetrates into the skin, preferably in a state in which the lipid peptide compound forms a self-assembled structure (also referred to as a self-assembled body), It enhances the fluidization of lipids in the skin and promotes permeation and percutaneous absorption of the active ingredient when the gel formed by the self-organized structure contains the active ingredient.

[Compositions that enhance lipid mobilization]
[Lipid peptide type compound]
By repeating at least two or more of the same or different amino acids in the lipid moiety consisting of an aliphatic group having 10 to 24 carbon atoms (10 to 24 carbon atoms in the entire lipid moiety) used in the composition of the present invention Examples of the lipid peptide-type compound to which the formed peptide portion is bound include compounds represented by the following formulas (1) to (3) (lipid peptides) or pharmaceutically acceptable salts thereof (hydrophobic site: A low-molecular-weight compound having a certain lipid portion and a peptide portion that is a hydrophilic portion) can be used.

In the above formula (1), R ¹ represents an aliphatic group having 9 to 23 carbon atoms, preferably R ¹ is a straight chain having 11 to 23 carbon atoms which may have 0 to 2 unsaturated bonds Desirably, it is an aliphatic group.
Specific examples of the lipid moiety (acyl group) composed of R ¹ and an adjacent carbonyl group include lauroyl group, dodecylcarbonyl group, myristoyl group, tetradecylcarbonyl group, palmitoyl group, margaroyl group, oleoyl group, and elaidoyl group. , a linoleoyl group, a stearoyl group, a vaxenoyl group, an octadecylcarbonyl group, an arachidoyl group, an eicosylcarbonyl group, a behenoyl group, an erucanoyl group, a docosylcarbonyl group, a lignoceyl group, a nervonoyl group, and the like. Examples include lauroyl, myristoyl, palmitoyl, margaroyl, stearoyl, oleoyl, elaidoyl and behenoyl groups.

In the above formula (1), R ² contained in the peptide portion represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms.
The above alkyl group having 1 to 4 carbon atoms and possibly having a branched chain having 1 or 2 carbon atoms means that the main chain has 1 to 4 carbon atoms and has a branched chain having 1 or 2 carbon atoms. means an alkyl group that may have, specific examples thereof include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group or tert-butyl group etc.
R ² above is preferably a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may have a branched chain of 1 carbon atom, more preferably a hydrogen atom.
An alkyl group having 1 to 3 carbon atoms and possibly having a branched chain having 1 carbon atom is an alkyl group having a main chain having 1 to 3 carbon atoms and possibly having a branched chain having 1 carbon atom. Specific examples thereof include methyl group, ethyl group, n-propyl group, i-propyl group, i-butyl group and sec-butyl group, preferably methyl group, i-propyl group, i-butyl group or sec-butyl group.

In formula (1) above, R ³ represents a —(CH ₂ )nX group. In the —(CH ₂ )nX group, n represents a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or a 5-membered ring group which may have 1 to 3 nitrogen atoms. Alternatively, it represents a 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.
In the —(CH ₂ )nX group representing R ³ above, X is preferably an amino group, a guanidino group, a carbamoyl group (—CONH ₂ group), a pyrrole group, an imidazole group, a pyrazole group or an indole group, and more An imidazole group is preferred. In the -(CH ₂ )nX group, n is preferably 1 or 2, more preferably 1.
Therefore, the —(CH ₂ )nX group is preferably an aminomethyl group, a 2-aminoethyl group, a 3-aminopropyl group, a 4-aminobutyl group, a carbamoylmethyl group, a 2-carbamoylethyl group, a 3- represents a carbamoylbutyl group, a 2-guanidinoethyl group, a 3-guanidinobutyl group, a pyrrolemethyl group, a 4-imidazolemethyl group, a pyrazolemethyl group, or a 3-indolemethyl group, more preferably a 4-aminobutyl group and a carbamoylmethyl group; 2-carbamoylethyl group, 3-guanidinobutyl group, 4-imidazolemethyl group or 3-indolemethyl group, more preferably 4-imidazolemethyl group.

A particularly suitable lipid peptide in the compound represented by the above formula (1) as a lipid peptide type compound is a compound formed from the following lipid portion and peptide portion (amino acid assembly portion). Amino acid abbreviations include alanine (Ala), asparagine (Asn), glutamine (Gln), glycine (Gly), histidine (His), isolesine (Ile), leucine (Leu), lysine (Lys), tryptophan (Trp ), representing valine (Val). : Lauroyl-Gly-His, Lauroyl-Gly-Gln, Lauroyl-Gly-Asn, Lauroyl-Gly-Trp, Lauroyl-Gly-Lys, Lauroyl-Ala-His, Lauroyl-Ala-Gln, Lauroyl-Ala-Asn, Lauroyl -Ala-Trp, Lauroyl-Ala-Lys; Myristoyl-Gly-His, Myristoyl-Gly-Gln, Myristoyl-Gly-Asn, Myristoyl-Gly-Trp, Myristoyl-Gly-Lys, Myristoyl-Ala-His, Myristoyl-Ala -Gln, Myristoyl-Ala-Asn, Myristoyl-Ala-Trp, Myristoyl-Ala-Lys; Palmitoyl-Gly-His, Palmitoyl-Gly-Gln, Palmitoyl-Gly-Asn, Palmitoyl-Gly-Trp, Palmitoyl-Gly-Lys , Palmitoyl-Ala-His, Palmitoyl-Ala-Gln, Palmitoyl-Ala-Asn, Palmitoyl-Ala-Trp, Palmitoyl-Ala-Lys; Stearoyl-Gly-His, Stearoyl-Gly-Gln, Stearoyl-Gly-Asn, Stearoyl -Gly-Trp, Stearoyl-Gly-Lys, Stearoyl-Ala-His, Stearoyl-Ala-Gln, Stearoyl-Ala-Asn, Stearoyl-Ala-Trp, Stearoyl-Ala-Lys.

Most preferred are Lauroyl-Gly-His, Lauroyl-Ala-His, Myristoyl-Gly-His, Myristoyl-Ala-His, Palmitoyl-Gly-His, Palmitoyl-Ala-His, Stearoyl-Gly-His, Stearoyl-Ala -His.

In formula (2) above, R ⁴ represents an aliphatic group having 9 to 23 carbon atoms, and preferred specific examples include the same groups as defined for R ¹ above.
In the above formula (2), R ⁵ to R ⁷ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms, or —(CH ₂ ) represents an nX group, preferably at least one or more of R ⁵ to R ⁷ represents a -(CH ₂ )nX group. n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or a 5- or 6-membered ring group which may have 1 to 3 nitrogen atoms, or a 5-membered ring and 6 represents a condensed heterocyclic group composed of membered rings. Preferred specific examples of R ⁵ to R ⁷ are the same groups as defined for R ² and R ³ above.

In the compound represented by the above formula (2), a suitable lipid peptide is a compound formed from the following lipid portion and peptide portion (amino acid assembly portion). Lauroyl-Gly-Gly-His, Myristoyl-Gly-Gly-His, Myristoyl-Gly-Gly-Gln, Myristoyl-Gly-Gly-Asn, Myristoyl-Gly-Gly-Trp, Myristoyl-Gly-Gly-Lys, Myristoyl- Gly-Ala-His, Myristoyl-Gly-Ala-Gln, Myristoyl-Gly-Ala-Asn, Myristoyl-Gly-Ala-Trp, Myristoyl-Gly-Ala-Lys, Myristoyl-Ala-Gly-His, Myristoyl-Ala- Gly-Gln, Myristoyl-Ala-Gly-Asn, Myristoyl-Ala-Gly-Trp, Myristoyl-Ala-Gly-Lys, Myristoyl-Gly-His-Gly, Myristoyl-His-Gly-Gly, Palmitoyl-Gly-Gly- His, palmitoyl-Gly-Gly-Gln, palmitoyl-Gly-Gly-Asn, palmitoyl-Gly-Gly-Trp, palmitoyl-Gly-Gly-Lys, palmitoyl-Gly-Ala-His, palmitoyl-Gly-Ala-Gln, Palmitoyl-Gly-Ala-Asn, Palmitoyl-Gly-Ala-Trp, Palmitoyl-Gly-Ala-Lys, Palmitoyl-Ala-Gly-His, Palmitoyl-Ala-Gly-Gln, Palmitoyl-Ala-Gly-Asn, Palmitoyl- Ala-Gly-Trp, Palmitoyl-Ala-Gly-Lys, Palmitoyl-Gly-His-Gly, Palmitoyl-His-Gly-Gly. Stearoyl-Gly-Gly-His.

Among these, the most preferred are lauroyl-Gly-Gly-His, myristoyl-Gly-Gly-His, palmitoyl-Gly-Gly-His, palmitoyl-Gly-His-Gly, palmitoyl-His-Gly-Gly, stearoyl -Gly-Gly-His.

In formula (3) above, R ⁸ represents an aliphatic group having 9 to 23 carbon atoms, and preferred specific examples thereof include the same groups as defined for R ¹ above.
In the above formula (3), R ⁹ to R ¹² are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms, or —(CH ₂ ) represents an nX group, preferably at least one of R ⁹ to R ¹² represents a -(CH ₂ )nX group. n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or a 5- or 6-membered ring group which may have 1 to 3 nitrogen atoms, or a 5-membered ring and 6 represents a condensed heterocyclic group composed of membered rings. Preferable specific examples of R ⁹ to R ¹² include the same groups as defined for R ² and R ³ above.

Therefore, in the compound represented by the above formula (3), preferred lipid peptide compounds, particularly preferred lipid peptides, include lauroyl-Gly-Gly-Gly-His, myristoyl-Gly-Gly-Gly-His, palmitoyl -Gly-Gly-Gly-His, Palmitoyl-Gly-Gly-His-Gly, Palmitoyl-Gly-
His-Gly-Gly, palmitoyl-His-Gly-Gly-Gly, stearoyl-Gly-Gly-Gly-His and the like.

In the present invention, the amount of the lipid peptide compound is, for example, 0.005 to 30% by mass, preferably 0.005 to 10% by mass, more preferably 0.05 to 5% by mass, relative to the total mass of the composition. %, more preferably 0.005 to 1 mass %.
The lipid peptide type compound used in the present invention consists of at least one compound (lipid peptide) represented by the above formulas (1) to (3) or a pharmaceutically usable salt thereof, and these compounds can be used alone or in combination of two or more.

[Active ingredient]
Active ingredients expected to promote penetration and percutaneous absorption of the composition containing the lipid peptide compound of the present invention include physiologically active ingredients blended in external skin preparations such as cosmetics, quasi-drugs, and pharmaceuticals. Substances, functional substances, and the like can be mentioned and can be included in the compositions of the present invention.
Active ingredients applicable to the present invention are not limited by the presence or absence of affinity for water, but are preferably water-soluble active ingredients.
For example, whitening agents, vitamins and derivatives thereof, hair growth agents, blood circulation promoters, stimulants, anti-gray hair agents, hormones, anti-wrinkle agents, anti-aging agents, tightening agents, cooling agents, warming agents, wounds Healing accelerator, stimulant, analgesic, cell activator, plant/animal/microorganism extract, antipruritic, exfoliating/dissolving agent, enzyme, nucleic acid, anti-inflammatory agent, anti-asthma, anti-chronic obstructive pulmonary disease, anti-allergy, immunomodulators, anti-infectives, anti-fungal agents, and the like.

Whitening agents include hydroquinone glycosides such as arbutin and α-arbutin and esters thereof; ascorbic acid, ascorbic acid phosphate salts such as sodium ascorbic acid phosphate and magnesium ascorbic acid phosphate; Ascorbic acid fatty acid esters such as tetraisopalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucosides such as ascorbic acid-2-glucoside and their fatty acid esters, ascorbic acid sulfates, tocopheryl ascorbyl phosphate Ascorbic acid derivatives such as; kojic acid, ellagic acid, tranexamic acid and its derivatives, ferulic acid and its derivatives, placenta extract, glutathione, oryzanol, butylresorcinol, oil-soluble chamomile extract, oil-soluble licorice extract, Nishikawayanagi extract, saxifrage extract plant extracts such as; 4-n-butylresorcinol (Rucinol), linoleic acid S (Rinolex S (registered trademark)), 4-methoxysalicylic acid potassium salt, adenosine-disodium phosphate, 5,5′-dipropyl-biphenyl- 2,2′-diol (magnolignan), dexpanthenol W, cetyl tranexamate hydrochloride, rhododenol are preferred.

Examples of vitamins and derivatives thereof include vitamin A such as retinol, retinol acetate, and retinol palmitate; Flavin adenine dinucleotide, cyanocobalamin, folic acids, nicotinic acid amide (niacinamide), nicotinic acids such as benzyl nicotinate, vitamin B group such as choline; vitamin C such as ascorbic acid and salts thereof such as sodium; vitamins D: vitamin E such as α, β, γ, δ-tocopherol; other vitamins such as pantothenic acid and biotin; ascorbic acid phosphate such as ascorbyl phosphate sodium salt and ascorbyl phosphate magnesium salt , ascorbic acid tetraisopalmitate, ascorbyl stearate, ascorbyl palmitate, ascorbyl dipalmitate, etc.; and fatty acid esters thereof, ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate, tocopheryl acetate, tocopherol linoleate, tocopherol ferulate, tocopherol phosphate, etc., tocotrienols, and other various vitamin derivatives are preferred.

Hair growth agents, blood circulation promoters, and stimulants include plant extracts and tinctures such as assembly extract, capsicum tincture, ginger tincture, ginger extract, cantharis tincture; , borneol, cyclanderate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, vitamin E and derivatives such as tocopherol nicotinate and tocopherol acetate, nicotinic acid, nicotinic acid amide (niacinamide), benzyl nicotinate , inositol hexanicotinate, nicotinic acid derivatives such as nicotine alcohol, allantoin, photosensitizer 301, photosensitizer 401, capronium chloride, pentadecanoic acid monoglyceride, flavanonol derivatives, stigmasterol or stigmastanol and its glycosides, minoxidil, international Preferred are ALK5 inhibitory compounds as described in Publication No. 2005/085241, WNT-5 inhibitory compounds as described in WO2003/086334.

Preferred anti-gray hair agents include kuhone, soapberry, saxifrage, and thyme.

Preferred hormones include estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone, and the like.

Other medicinal agents such as anti-wrinkle agents, anti-aging agents, tightening agents, cooling agents, warming agents, wound healing promoting agents, stimulating agents, analgesics, and cell activators include retinols, retinoic acids, and retinoin. tocopheryl acid; lactic acid, glycolic acid, gluconic acid, fruit acid, salicylic acid and derivatives such as glycosides and esters thereof, hydroxycapric acid, long-chain α-hydroxy fatty acids, α- or long-chain α-hydroxy fatty acid cholesteryl β-hydroxy acids and their derivatives; γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid; carnitine; carnosine; creatine; ceramides, sphingosines; caffeine, xanthine, etc. and their derivatives; , astaxanthin, lutein, α-lipoic acid, platinum nanocolloids, antioxidants and active oxygen scavengers such as fullerenes; catechins; flavones such as quercetin; isoflavones; gallic acid and ester sugar derivatives; Polyphenols such as anthocyanidins, chlorogenic acid, and apple polyphenols; derivatives such as rutin and glycosides; derivatives such as hesperidin and glycosides; lignan glycosides; shogaol, gingerol; menthol, cedrol and other flavoring substances and their derivatives; capsaicin, vanillin and their derivatives; insect repellents such as diethyltoluamide; .

Plant/animal/microorganism extracts include iris extract, angelica keiskei extract, asunaro extract, asparagus extract, avocado extract, amacha extract, almond extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, and ginkgo biloba extract. , inchkou extract, fennel extract, turmeric extract, oolong tea extract, urticaria extract, age extract, Echinashi leaf extract, trillium extract, Scutellaria root extract, Phellodendron bark extract, Coptis extract, Barley extract, Panax ginseng extract, Hypericum extract, Dead nettle extract, Ononis extract , Dutch mustard extract, orange extract, seawater dried matter, seaweed extract, oyster leaf extract, oyster extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, kakkon extract, chamomile extract, oil-soluble chamomile extract, carrot extract, wormwood extract, oat extract, karkade extract, licorice extract, oil-soluble licorice extract, kiwi extract, kiwi extract, cloud ear extract, cinchona extract, cucumber extract, paulownia leaf extract, guanosine, guava extract, kujin extract, gardenia extract, kumazasa extract, clara extract, walnut Extract, Chestnut extract, Grapefruit extract, Clematis extract, Black rice extract, Brown sugar extract, Black vinegar, Chlorella extract, Mulberry extract, Gentian extract, Gennoshoko extract, Black tea extract, Yeast extract, Koboku extract, Coffee extract, Burdock extract, Rice extract, Rice Fermented extract, rice bran fermented extract, rice germ oil, comfrey extract, collagen, cowberry extract, rhinoceros extract, rhinoceros extract, rhinoceros extract, saffron extract, salvia extract, soapwort extract, bamboo grass extract, hawthorn extract, sansha extract, Japanese pepper extract, shiitake extract, reed extract, licorice extract, perilla extract, linden extract, meadowsweet extract, jatoba extract, peony extract, ginger extract, calamus root extract, white birch extract, white fungus extract, horsetail extract, stevia extract, fermented stevia, Nishikawayanagi extract, Ivy extract, hawthorn extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, neem extract, jersey extract, sage extract, rhubarb extract, dai Sunflower extract, turmeric extract, thyme extract, dandelion extract, lichen extract, tea extract, clove extract, cinnamon extract, chimp extract, tea tree oil, sweet tea extract, capsicum extract, angelica extract, calendula officinalis extract, tonin extract, spruce extract, Houttuynia cordata extract, tomato Extract, Natto extract, Carrot extract, Garlic extract, Novara extract, Hibiscus extract, Bakumondou extract, Lotus extract, Parsley extract, Birch extract, Honey, Hamamelis extract, Parietalia extract, Hikiokoshi extract, Bisabolol, Hinoki extract, Bifidobacterium extract, Loquat extract, coltsfoot extract, coltsfoot extract, coltsfoot extract, bukuryo extract, butcher bloom extract, grape extract, grape seed extract, propolis, loofah extract, safflower extract, peppermint extract, bodaiju extract, botan extract, hop extract, mica extract, pine extract, horse chestnut extract , Asian skunk cabbage extract, soapberry extract, melissa extract, mozuku extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, yuzu extract, lily extract, yokuinin extract, mugwort extract, lavender extract, green tea extract, eggshell membrane extract, apple extract, rooibos tea extract , Reishi extract, lettuce extract, lemon extract, forsythia extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, burnet extract and the like are preferred.

Antipruritics include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, substance-P inhibitors and the like.

Examples of exfoliating/dissolving agents include salicylic acid, sulfur, resorcinol, selenium sulfide, pyridoxine, and the like.

Enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, protease and the like.

Preferred nucleic acids include ribonucleic acid and its salts, deoxyribonucleic acid and its salts, and disodium adenosine triphosphate.

Antiphlogistic agents and anti-inflammatory agents include glycyrrhizic acid and its derivatives, glycyrrhizic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, ketoprofen, ibuprofen, diclofenac, loxoprofen, celecoxib, infliximab, etanercept, zinc oxide, hydrocortisone acetate, Prednisone, diphedramine hydrochloride, chlorpheniramine maleate; plant extracts such as peach leaf extract and mugwort leaf extract are preferred.

Anti-asthma, anti-chronic obstructive pulmonary disease, anti-allergic, and immunomodulators include aminophylline, theophylline, steroids (fluticasone, beclomethasone, etc.), leukotriene antagonists, thromboxane inhibitors, intal, and β2 agonists. (formoterol, salmeterol, albuterol, tulobuterol, clenbuterol, epinephrine, etc.), tiotropium, ipratropium, dextromethorphan, dimemorphan, bromhexine, tranilast, ketotifen, azelastine, cetirizine, chlorpheniramine, mequitazine, tacrolimus, cyclosporine, sirolimus, methotrexate , cytokine modulators, interferon, omalizumab, protein/antibody preparations are preferred.

Preferred anti-infective agents and anti-fungal agents include oseltamivir, zanamivir and itraconazole.

In addition to these, the standards for cosmetic raw materials, the standards for ingredients by cosmetic type, the list of ingredients displayed by the Japan Cosmetic Industry Association, the INCI dictionary (The International Cosmetic
Ingredient Dictionary and Handbook), Standards for Quasi-drug Ingredients, Japanese Pharmacopoeia, Standards for Pharmaceutical Additives, Food Additives Standards, etc., and International Patent Classification IPC belongs to the classification of A61K7 and A61K8. and known cosmetic ingredients, pharmaceutical ingredients, food ingredients, etc., such as ingredients described in foreign patent publications and patent publications (including published publications and republished publications).

[Other ingredients]
The composition of the present invention can contain water, alcohol, polyhydric alcohol, or a mixed solution thereof, in addition to the lipid peptide compound and, if desired, the active ingredient.

Examples of the water include purified water, purified water, hard water, soft water, natural water, deep sea water, electrolytic alkaline ionized water, electrolytic acidic ionized water, ionized water, and cluster water.

The alcohol is a monohydric alcohol, for example, an alcohol having 1 to 6 carbon atoms that dissolves in water at any ratio, specifically methanol, ethanol, 2-propanol, i-butanol, etc., and higher Alcohols, specifically oleyl alcohol, phenoxy alcohol and the like.

The above-mentioned polyhydric alcohol is an alcohol having a valence of 2 or more, and examples thereof include propylene glycol, 1,3-butanediol, 2-ethyl-1,3-hexanediol, glycerin, isopentyldiol, ethylhexanediol, erythrulose. , ozonated glycerin, caprylyl glycol, glycol, (C15-18) glycol, (C20-30) glycol, glycerin, diethylene glycol, diglycerin, dithiaoctanediol, dipropylene glycol (DPG), thioglycerin, 1,10 -decanediol, decylene glycol, triethylene glycol, trimethylhydroxymethylcyclohexanol, phytantriol, phenoxypropanediol, 1,2-butanediol, 2,3-butanediol, butylethylpropanediol, 1,2-hexane Diols, hexylene glycol, pentylene glycol, methylpropanediol, menthanediol, lauryl glycol and polypropylene glycol.

In the present invention, when a polyhydric alcohol is included, its content is, for example, 0.001% by mass to 60% by mass, preferably 0.001% by mass to 30% by mass, relative to the total mass of the composition. Preferably, it can be 0.01% by mass to 30% by mass.
In addition, in this invention, when a polyhydric alcohol is included, a polyhydric alcohol can be used individually or in combination of 2 or more types.

[Other additives]
In addition to the above components, the composition of the present invention may further contain widely known additives as long as they do not impair the properties of the present invention. In this case, it is particularly preferable to use a pharmaceutically acceptable additive, that is, a biologically acceptable additive. It can contain additives that can be used as
In addition, the composition of the present invention may contain the components listed above as [active ingredients].

Examples of additives that can be added to external skin preparations such as cosmetics, quasi-drugs, and pharmaceuticals include pigments, oily bases, moisturizers, texture improvers, surfactants, polymers, thickening/gelling agents, Solvents, antioxidants, reducing agents, oxidizing agents, preservatives, antibacterial agents, bactericides, chelating agents, pH adjusters, acids, alkalis, powders, inorganic salts, ultraviolet absorbers, antiperspirants, cooling agents, astringents agents, fragrances, pigments, coloring agents, dyes, and the like.
When these other additives are included, the content thereof may vary depending on the type thereof, but for example, 0.001% by mass to 20% by mass, or 0.01% by mass to 20% by mass, relative to the total mass of the composition. It can be about 10% by mass.

Pigments include inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as red iron oxide (red iron oxide) and iron titanate; inorganic brown pigments such as γ-iron oxide; Inorganic yellow pigments; Inorganic black pigments such as black iron oxide and low order titanium oxide; Inorganic purple pigments such as mango violet and cobalt violet; Inorganic green pigments such as chromium oxide, chromium hydroxide and cobalt titanate; , inorganic blue pigments such as Prussian blue; titanium oxide-coated mica, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, colored titanium oxide-coated mica, bismuth oxychloride, pearl pigments such as fish scale foil; talc, sericite, mica, Extender pigments such as kaolin, calcium carbonate, magnesium carbonate, silicic anhydride, barium sulfate, and aluminum hydroxide; metal powder pigments such as aluminum powder, copper powder, and gold; surface-treated inorganic and metal powder pigments; zirconium, barium, or aluminum lakes organic pigments such as organic pigments; surface-treated organic pigments;

Oily bases include higher (polyhydric) alcohols such as oleyl alcohol, jojoba alcohol, chimyl alcohol, selachyl alcohol, batyl alcohol, hexyldecanol, isostearyl alcohol, 2-octyldodecanol, dimer diol; benzyl alcohol, etc. aralkyl alcohol and its derivatives; stearic acid, isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linoleic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid , anteisohenicosanoic acid, long-chain branched fatty acid, dimer acid, hydrogenated dimer acid, etc.; liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene , squalane, olive-derived squalane, squalene, vaseline, solid paraffin and other hydrocarbons; candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, montan wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Waxes such as Fischer-Tropsch wax, polyethylene wax, ethylene-propylene copolymer; coconut oil, palm oil, palm kernel oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil , macadamia nut oil, hazelnut oil, kukui nut oil, rosehip oil, meadowfoam oil, persic oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil , rice bran oil, cacao butter, shea butter, hydrogenated coconut oil, hydrogenated castor oil, jojoba oil, hydrogenated jojoba oil, grapeseed oil, apricot oil (apricot kernel oil), camellia oil and other vegetable oils; beef tallow, milk fat , horse fat, egg yolk oil, mink oil, turtle oil; animal waxes such as whale wax, lanolin, orange roughy oil; liquid lanolin, reduced lanolin, adsorbed refined lanolin, lanolin acetate, liquid acetic acid Lanolins such as lanolin, hydroxyl lanolin, polyoxyethylene lanolin, lanolin fatty acid, hard lanolin fatty acid, lanolin alcohol, lanolin acetate alcohol, and acetic acid (cetyl/lanolyl) ester; cholesterol, dihydrocholesterol sterols such as sterols, lanosterol, dihydrolanosterol, phytosterol, cholic acid; sapogenins; saponins; cholesteryl/behenyl/octyldodecyl), di(cholesteryl/octyldodecyl) N-lauroyl-L-glutamate, di(phytosteryl/behenyl/octyldodecyl) N-lauroyl-L-glutamate, di(phytosteryl) N-lauroyl-L-glutamate /octyldodecyl), acyl sarcosine alkyl esters such as N-lauroyl sarcosine isopropyl, cholesteryl 12-hydroxystearate, macadamia nut oil fatty acid cholesteryl, macadamia nut oil fatty acid phytosteryl, phytosteryl isostearate, soft lanolin fatty acid cholesteryl, hard lanolin fatty acid cholesteryl, long chain sterol esters such as branched fatty acid cholesteryl and long-chain α-hydroxy fatty acid cholesteryl; lipid complexes such as phospholipid/cholesterol complex and phospholipid/phytosterol complex; , cetyl palmitate, octyldodecyl palmitate, cetyl octanoate, hexyldecyl octanoate, isotridecyl isononanoate, isononyl isononanoate, octyl isononanoate, isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyldodecyl neodecanoate, olein Oleyl acid, octyldodecyl oleate, octyldodecyl ricinoleate, octyldodecyl lanolin fatty acid, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrogenated castor oil isostearate, ethyl oleate, ethyl avocado oil, isopropyl myristate, palmitic acid Monoalcohols such as isopropyl, octyl palmitate, isopropyl isostearate, lanolin fatty acid isopropyl, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate, diisopropyl adipate, dibutyloctyl sebacate, diisobutyl adipate, dioctyl succinate, triethyl citrate, etc. Carboxylic acid esters; cetyl lactate, dimalate Oxyacid esters such as isostearyl and hydrogenated castor oil monoisostearate; Acid) glyceryl, tri (caprylic/capric/myristic/stearic) glyceryl, hydrogenated rosin triglyceride (hydrogenated ester gum), rosin triglyceride (ester gum), eicosane diacid glyceryl behenate, trimethylolpropane trioctanoate , trimethylolpropane triisostearate, neopentyl glycol dioctoate, neopentyl glycol dicaprate, 2-butyl-2-ethyl-1,3-propanediol dioctoate, propylene glycol dioleate, pentaerythrityl tetraoctanoate, hydrogen Added rosin pentaerythrityl, ditrimethylolpropane triethylhexanoate, (isostearate/sebacate) ditrimethylolpropane, pentaerythrityl triethylhexanoate, (hydroxystearate/stearate/rosinate) dipentaerythrityl, diglyceryl diisostearate, tetra Polyglyceryl isostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 deca (erucic acid/isostearic acid/ricinoleic acid), diglyceryl oligoester (hexyldecanoic acid/sebacic acid), glycol distearate (ethylene glycol distearate), dineopentanoic acid Polyhydric alcohol fatty acid esters such as 3-methyl-1,5-pentanediol and 2,4-diethyl-1,5-pentanediol dineopentanoate; diisopropyl dimer dilinoleate, diisostearyl dimer dilinoleate, dimer Di(isostearyl/phytosteryl) linoleate, dimer dilinoleic acid (phytosteryl/behenyl), dimer dilinoleate (phytosteryl/isostearyl/cetyl/stearyl/behenyl), dimer dilinoleyl dimer dilinoleate, dimer diisostearate Dimer acids or dimer diol derivatives such as linoleyl, dimer dilinoleyl hydrogenated rosin condensate, dimer dilinoleic acid hydrogenated castor oil, hydroxyalkyl dimer dilinoleyl ether; coconut oil fatty acid monoethanolamide (coca amide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (Lauramide MEA), lauric acid diethanolamide (Lauramide DEA), lauric acid monoisopropanolamide (Lauramide MIPA), palmitic acid monoethanolamide (Partamide MEA), fatty acid alkanolamides such as palmitic acid diethanolamide (partamide DEA), coconut oil fatty acid methylethanolamide (cocamide methyl MEA); dimethicone (dimethylpolysiloxane), highly polymerized dimethicone (highly polymerized dimethylpolysiloxane), cyclomethicone ( Cyclic dimethylsiloxane, decamethylcyclopentasiloxane (also known as cyclopentasiloxane), phenyltrimethicone, diphenyldimethicone, phenyldimethicone, stearoxypropyldimethylamine, (aminoethylaminopropylmethicone/dimethicone) copolymers, dimethiconol, dimethiconol crosspolymer , silicone resin, silicone rubber, amino-modified silicone such as aminopropyl dimethicone and amodimethicone, cation-modified silicone, polyether-modified silicone such as dimethicone copolyol, polyglycerin-modified silicone, sugar-modified silicone, carboxylic acid-modified silicone, phosphoric acid-modified silicone, sulfate-modified silicone, alkyl-modified silicone, fatty acid-modified silicone, alkyl ether-modified silicone, amino acid-modified silicone, peptide-modified silicone, fluorine-modified silicone, cation-modified and polyether-modified silicone, amino-modified and polyether-modified silicone, alkyl-modified and Silicones such as polyether-modified silicones and polysiloxane/oxyalkylene copolymers; fluorine-based oils such as perfluorodecane, perfluorooctane, and perfluoropolyethers are preferred.

Moisturizers and texture improvers include polyols such as glycerin, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, dipropylene glycol, polypropylene glycol, and ethylene glycol/propylene glycol copolymers. its polymers; glycol alkyl ethers such as diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol dibutyl ether; (eicosanedioic acid/tetradecanedioic acid) polyglyceryl-10, tetradecane di water-soluble esters such as acid polyglyceryl-10; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, maltitol; glucose, fructose, galactose, mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, Trehalose, lactose, raffinose, gluconic acid, glucuronic acid, cyclodextrins (α-, β-, γ-cyclodextrins and modified cyclodextrins such as maltosylation and hydroxyalkylation), β-glucan, chitin, chitosan, Sugars and derivatives thereof such as heparin and its derivatives, pectin, arabinogalactan, dextrin, dextran, glycogen, ethyl glucoside, glucosylethyl methacrylate polymer or copolymer; hyaluronic acid, sodium hyaluronate; sodium chondroitin sulfate; mucoitin Sulfuric acid, caronine sulfate, keratosulfate, dermatan sulfate; Tremella fungus extract, Tremella fungus polysaccharide; Fucoidan; Tuberose polysaccharide or naturally occurring polysaccharide; -Pyrrolidone-5-carboxylic acid and salts thereof such as sodium; betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, tyrosine, β-alanine, threonine, glutamic acid, glutamine, asparagine , aspartic acid, cysteine, methionine, leucine, isoleucine, valine, tryptophan, histidine, taurine and other amino acids and their salts; collagen, fish-derived collagen, atelocollagen, gelatin, gills stin, collagen degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin degrading peptide, keratin degrading peptide, hydrolyzed keratin, conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, hydrolyzed lauroyl Protein peptides such as silk sodium, soybean proteolytic peptides, wheat proteolytic peptides, hydrolyzed wheat proteins, casein-degrading peptides, acylated peptides and derivatives thereof; acylated peptides such as palmitoyl oligopeptides, palmitoyl pentapeptides and palmitoyl tetrapeptides silylated peptides; lactic acid bacteria culture, yeast extract, eggshell membrane protein, bovine submandibular gland mucin, hypotaurine, sesame lignan glycoside, glutathione, albumin, whey; choline chloride, phosphorylcholine; placenta extract, collagen, Aloe extract, hamamelis water, loofah water, chamomilla extract, licorice extract, comfrey extract, silk extract, rose rose extract, yarrow extract, eucalyptus extract, melilot extract and other animal and plant extracts, natural ceramide (type 1, 2, 3, 4, 5, 6), ceramides such as hydroxyceramides, pseudoceramides, glycosphingolipids, ceramides, and sugar-ceramide-containing extracts are preferred.

Preferred surfactants include anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, polymeric surfactants, and the like.
Examples of preferred surfactants include anionic surfactants such as fatty acid salts such as potassium laurate and potassium myristate; alkyl sulfate salts such as sodium lauryl sulfate, triethanolamine lauryl sulfate and ammonium lauryl sulfate; Polyoxyethylene alkyl sulfates such as sodium laureth sulfate and triethanolamine laureth sulfate; sodium cocoyl methyl taurate, potassium cocoyl methyl taurate, sodium lauroyl methyl taurate, sodium myristoyl methyl taurate, sodium lauroyl methyl alanine, sodium lauroyl sarcosinate, lauroyl sarcosyntriate Ethanolamine, acyl N-methyl amino acid salts such as sodium methylalanine lauroyl glutamate; sodium cocoyl glutamate, triethanolamine cocoyl glutamate, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium stearoyl glutamate, ditriethanolamine palmitoyl aspartate, cocoyl alanine triethanol Acyl amino acid salts such as amines; Polyoxyethylene alkyl ether acetates such as sodium laureth acetate; Succinic acid ester salts such as sodium lauroyl monoethanolamide succinate; Fatty acid alkanolamide ether carboxylates; Amine sulfates; fatty acid alkanolamide sulfates; fatty acid glyceride sulfates such as hydrogenated coconut oil fatty acid sodium glycerol sulfate; alkylbenzene polyoxyethylene sulfates; olefin sulfonates such as sodium α-olefin sulfonate; Alkyl sulfosuccinates such as dioctyl sodium sulfosuccinate; Alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate; sodium tetradecylbenzene sulfonate, Alkylbenzenesulfonates such as tetradecylbenzenesulfonate triethanolamine; Alkylnaphthalenesulfonates; Alkanesulfonates; α-sulfo fatty acid methyl ester salts; Acyl isethionates; Laureth Alkyl ether phosphate salts such as sodium phosphate, sodium dilaureth phosphate, sodium trilaureth phosphate, sodium monooleth phosphate; alkyl phosphate salts such as potassium lauryl phosphate; sodium caseinate; alkylaryl ether phosphates; fatty acid amides ether phosphate; phospholipids such as phosphatidylglycerol, phosphatidylinositol and phosphatidic acid; silicone anionic surfactants such as carboxylic acid-modified silicone, phosphoric acid-modified silicone and sulfate-modified silicone;
Nonionic surfactants include laureth (polyoxyethylene lauryl ether), ceteth (polyoxyethylene cetyl ether), steareth (polyoxyethylene stearyl ether), beheneth (polyoxyethylene behenyl ether), isosteareth (polyoxyethylene isostearyl ether), octyldodeceth (polyoxyethylene octyldodecyl ether), and other polyoxyethylene alkyl ethers with various oxyethylene group addition moles; polyoxyethylene alkylphenyl ether; polyoxyethylene hardened castor Oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearate diester, polyoxyethylene hydrogenated castor oil Castor oil and hydrogenated castor oil derivatives such as maleic acid; Polyoxyethylene phytosterol; Polyoxyethylene cholesterol; Polyoxyethylene cholestanol; Polyoxyethylene lanolin; Polyoxyethylene reduced lanolin; Polyoxyethylene/polyethylene such as oxyethylene/polyoxypropylene 2-decyltetradecyl ether, polyoxyethylene/polyoxypropylene monobutyl ether, polyoxyethylene/polyoxypropylene hydrogenated lanolin, polyoxyethylene/polyoxypropylene glycerin ether Oxypropylene alkyl ether; Polyoxyethylene/polyoxypropylene glycol; PPG-9 diglyceryl (poly)glycerin Polyoxypropylene glycol; Glyceryl stearate, Glyceryl isostearate, Glyceryl palmitate, Glyceryl myristate, Glyceryl oleate, Glycerin fatty acid partial esters such as coconut oil fatty acid glyceryl, monocottonseed fatty acid glycerin, glyceryl monoerucate, glycerin sesquioleate, α,α'-pyroglutamic acid glyceryl monostearate, glyceryl monostearate malic acid; polyglyceryl-2 stearate, 3, 4, 5, 6, 8, 10, polyglyceryl-6, 10, polyglyceryl-2 tristearate, polyglyceryl-10 destearate, polyisostearate Liglyceryl-2, 3, 4, 5, 6, 8, 10, polyglyceryl-2 diisostearate (diglyceryl diisostearate), 3, 10, polyglyceryl-2 triisostearate, tetraisostearate Polyglyceryl-2 acid, polyglyceryl-10 decaisostearate, polyglyceryl-oleate 2, 3, 4, 5, 6, 8, 10, polyglyceryl-6 dioleate, polyglyceryl-2 trioleate, decaolein Polyglycerol fatty acid esters such as polyglyceryl-10; ethylene glycol mono fatty acid esters such as ethylene glycol monostearate; propylene glycol mono fatty acid esters such as propylene glycol monostearate; pentaerythritol partial fatty acid esters; sorbitol partial fatty acid esters; Partial fatty acid ester; maltitol ether; sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, penta-2-ethylhexyl dioleate Sorbitan fatty acid esters such as glycerol sorbitan, diglycerol sorbitan tetra-2-ethylhexyl acid; sucrose caprate, sucrose laurate, sucrose myristate, sucrose palmitate, sucrose stearate, sucrose Sucrose esters such as oleate, sucrose arachidate and sucrose behenate, methyl glucoside fatty acid esters, sugar derivative partial esters such as trehalose undecylenate; alkyl glucosides such as caprylyl glucoside; alkyl polyglycosides; lanolin alcohol reduced lanolin; polyoxyethylene fatty acid mono- and diesters such as polyoxyethylene distearate, polyethylene glycol diisostearate, polyoxyethylene monooleate, polyoxyethylene dioleate; polyoxyethylene/propylene glycol fatty acid esters ; polyoxyethylene glycerin fatty acid esters such as polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate; polyoxyethylene sorbitan monooleate, polyoxyethylene sol Polyoxyethylene sorbitan fatty acid esters such as bitan monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan tetraoleate; polyoxyethylene sorbitol monolaurate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitol pentaoleate polyoxyethylene sorbitol fatty acid esters such as polyoxyethylene sorbitol monostearate; polyoxyethylene methyl glucoside fatty acid esters; polyoxyethylene alkyl ether fatty acid esters; polyoxyethylene animal and vegetable oils and fats such as polyoxyethylene sorbitol beeswax; Alkyl glyceryl ethers such as glyceryl ether, chimyl alcohol, selachyl alcohol, and batyl alcohol; polyhydric alcohol alkyl ether; polyoxyethylene alkylamine; tetrapolyoxyethylene/tetrapolyoxypropylene-ethylenediamine condensates; saponin, sophorolipid Natural surfactants such as polyoxyethylene fatty acid amides; coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide ( Lauramide DEA), lauric acid monoisopropanolamide (Lauramide MIPA), palmitic acid monoethanolamide (Partamide MEA), palmitic acid diethanolamide (Partamide DEA), fatty acid alkanolamides such as coconut oil fatty acid methylethanolamide (cocamide methyl MEA); Alkyldimethylamine oxides such as lauramine oxide, cocamine oxide, stearamine oxide, and behenamine oxide; alkylethoxydimethylamine oxides; polyoxyethylene alkylmercaptans; Examples include silicone-based nonionic surfactants such as copolymers, polyglycerin-modified silicones, and sugar-modified silicones.
Cationic surfactants include alkyltrimethylammonium chlorides such as behentrimonium chloride, steartrimonium chloride, cetrimonium chloride and lauryltrimonium chloride; alkyltrimethylammonium bromides such as stearyltrimonium bromide; and distearyldimonium chloride. , Dialkyldimethylammonium chloride such as dicocodimonium chloride; Fatty acid amide amines such as stearamidopropyldimethylamine, stearamidoethyldiethylamine and salts thereof; Alkyl ether amines such as stearoxypropyldimethylamine and salts or quaternary salts thereof; Ethyl sulfate Long-chain branched fatty acid (12-31) fatty acid amide type quaternary ammonium salts such as aminopropylethyldimethylammonium, ethyl sulfate lanolin fatty acid aminopropylethyldimethylammonium; polyoxyethylene alkylamines and their salts or quaternary salts; alkylamine salts fatty acid amide guanidinium salts; alkyl ether amine monium salts; alkyltrialkylene glycol ammonium salts; benzalkonium salts; benzethonium salts; pyridinium salts such as cetylpyridinium chloride; morphonium salts; polyamine fatty acid derivatives; silicone cationic surfactants such as amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cation-modified silicones, cation-modified and polyether-modified silicones, amino-modified and polyether-modified silicones etc.
Amphoteric surfactants include N-alkyl-N,N-dimethyl amino acid betaines such as lauryl betaine (betaine lauryldimethylaminoacetate); fatty acid amide alkyl-N,N-dimethyl such as cocamidopropyl betaine and lauramidopropyl betaine Amino acid betaines; imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkylsulfobetaines such as alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; phosphate-type betaines such as alkyldimethylaminoethanol phosphate ; Sphingophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, lysolecithin, hydrogenated soybean phospholipids, partially hydrogenated soybean phospholipids, hydrogenated egg yolk phospholipids, partially hydrogenated egg yolk phospholipids, hydroxylated lecithin, etc. phospholipids; and silicone-based amphoteric surfactants.
Preferred polymer surfactants include polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, acrylic acid/methacrylate alkyl copolymers, and various silicone surfactants.

Guar gum, locust bean gum, queen seed, carrageenan, galactan, gum arabic, tara gum, tamarind, farcereran, karaya gum, tororo mallow, cara gum, tragacanth gum, pectin, pectic acid and sodium Salts such as salts, salts such as alginic acid and sodium salts, mannan; starches such as rice, corn, potato, wheat; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salts, xanthan gum, pullulan, gellan gum, chitin , chitosan, agar, cassava extract, chondroitin sulfate, casein, collagen, gelatin, albumin; methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and salts thereof such as sodium, methylhydroxypropylcellulose, cellulose sulfate Cellulose and its derivatives such as sodium, dialkyldimethylammonium sulfate cellulose, crystalline cellulose, and cellulose powder; starch-based polymers such as soluble starch, carboxymethyl starch, methylhydroxypropyl starch, methyl starch, hydroxypropyltrimonium chloride starch, octenylsuccinic acid Starch derivatives such as corn starch aluminum; Alginic acid derivatives such as sodium alginate and propylene glycol alginate; , polyoxyethylene / polyoxypropylene copolymer; (methacryloyloxyethyl carboxybetaine / alkyl methacrylate) copolymer, amphoteric methacrylic acid ester copolymer such as (acrylates / stearyl acrylate / methacrylate ethylamine oxide) copolymer; (dimethicone / vinyl dimethicone) crosspolymer, (alkyl acrylate / diacetone acrylamide) copolymer, (alkyl acrylate / diacetone acrylamide) copolymer AMP; partially saponified polyvinyl acetate, maleic acid copolymer; vinylpyrrolidone-dialkylamino methacrylate Alkyl copolymer; acrylic resin alkanolamine; poly ester, water-dispersible polyester; polyacrylamide; polyacrylic acid ester copolymer such as polyethyl acrylate, carboxyvinyl polymer, polyacrylic acid and salts such as sodium salt thereof, acrylic acid/methacrylic acid ester copolymer; Acrylic acid/alkyl methacrylate copolymer; cationized cellulose such as Polyquaternium-10, diallyldimethylammonium chloride/acrylamide copolymer such as Polyquaternium-7, acrylic acid/diallyldimethylammonium chloride copolymer such as Polyquaternium-22 , acrylic acid/diallyldimethylammonium chloride/acrylamide copolymer such as polyquaternium-39, acrylic acid/cationized methacrylic acid ester copolymer, acrylic acid/cationized methacrylic acid amide copolymer, polyquaternium-47, etc. Acrylic acid/methyl acrylate/chlorinated methacrylamidopropyltrimethylammonium copolymer, chlorinated methacrylic acid choline ester polymer; cationized polysaccharides such as cationized oligosaccharide, cationized dextran, guar hydroxypropyltrimonium chloride; polyethyleneimine; Cationic polymer; polymer of 2-methacryloyloxyethylphosphorylcholine such as polyquaternium-51 and copolymer with butyl methacrylate copolymer; acrylic resin emulsion, polyethyl acrylate emulsion, polyacryl alkyl ester emulsion, polyvinyl acetate Polymer emulsions such as resin emulsions, natural rubber latex, synthetic latex; nitrocellulose; polyurethanes and various copolymers;
Various silicones; various silicone copolymers such as acrylic-silicone graft copolymers; various fluorine-based polymers; 12-hydroxystearic acid and its salts; dextrin fatty acid esters such as dextrin palmitate and dextrin myristate; Acid, fumed silica (ultrafine silicic anhydride), aluminum magnesium silicate, sodium magnesium silicate, metal soap, dialkyl phosphate metal salt, bentonite, hectorite, organic modified clay mineral, sucrose fatty acid ester, fructooligosaccharide fatty acid Esters are preferred. Among the above examples, cellulose and its derivatives, alginic acid and its salts, polyvinyl alcohol, hyaluronic acid and its salts, or collagen are preferred.

Solvents include lower alcohols such as ethanol, 2-propanol (isopropyl alcohol), butanol and isobutyl alcohol; glycols such as propylene glycol, diethylene glycol, dipropylene glycol and isopentyldiol; diethylene glycol monoethyl ether (ethoxydiglycol). , ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, triethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, propylene glycol monoethyl ether, dipropylene glycol monoethyl ether; ethylene glycol monoethyl ether; Glycol ether esters such as acetate, diethylene glycol monoethyl ether acetate, propylene glycol monoethyl ether acetate; glycol esters such as diethoxyethyl succinate and ethylene glycol disuccinate; benzyl alcohol, benzyloxyethanol, propylene carbonate, dialkyl carbonate , acetone, ethyl acetate, N-methylpyrrolidone; toluene and the like are preferred.

Antioxidants (antioxidants) include tocopherol (vitamin E), tocopherol derivatives such as tocopherol acetate; dibutylhydroxytoluene (BHT), butylhydroxyanisole) BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and/or derivatives thereof; erythorbic acid and derivatives thereof; sulfites such as sodium sulfite; hydrogen sulfites such as sodium hydrogen sulfite; thiosulfates such as sodium thiosulfate; , thiourea, thioglycolic acid, and cysteine hydrochloride are preferred.

Preferred reducing agents include thioglycolic acid, cysteine, cysteamine, and the like.

Preferred examples of the oxidizing agent include aqueous hydrogen peroxide, ammonium persulfate, sodium bromate, and percarbonate.

Antiseptics, antibacterial agents, and disinfectants include hydroxybenzoic acid and its salts or esters such as methylparaben, ethylparaben, propylparaben, and butylparaben; salicylic acid; sodium benzoate; phenoxyethanol; isothiazolinone derivatives such as linone; imidazolinium urea; dehydroacetic acid and its salts; phenols; halogenated bisphenols such as triclosan, acid amides, quaternary ammonium salts; Benzethonium, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; other phenols such as phenol, isopropylphenol, cresol, thymol, parachlorophenol, phenylphenol, phenylphenol sodium; phenylethyl alcohol, photosensitizer , antibacterial zeolites, and silver ions are preferred.

Chelating agents include ethylenediaminetetraacetic acid (EDTA), EDTA2Na, EDT
Edetate (ethylenediaminetetraacetate) such as A3Na and EDTA4Na; hydroxyethylethylenediaminetriacetate such as HEDTA3Na; pentetate (diethylenetriaminepentaacetate); phytic acid; Salts; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, citric acid, alanine, dihydroxyethylglycine, gluconic acid, ascorbic acid, succinic acid, and tartaric acid are preferred It is mentioned as a thing.

pH adjusters, acids and alkalis include ascorbic acid, citric acid, sodium citrate, lactic acid, sodium lactate, potassium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric acid, fumaric acid, phosphoric acid, Hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propane Diol, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia, guanidine carbonate and ammonium carbonate are preferred.

Powders include mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, red mica, biotite, permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, silicic acid. Barium, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, zeolite, barium sulfate, calcined calcium sulfate, calcium phosphate such as tricalcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder, bentonite, smectite , clay, mud, metal soap (e.g. zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, red iron oxide, yellow iron oxide, black iron oxide, ultramarine blue, Prussian blue, carbon black, titanium oxide, fine and ultrafine particles Titanium oxide, zinc oxide, fine and ultrafine zinc oxide, alumina, silica, fumed silica (ultrafine silicic anhydride), titanium mica, fish scale foil, boron nitride, photochromic pigment, synthetic fluorine phlogopite, fine composite powder Inorganic powders of various sizes and shapes such as gold, silver, platinum, aluminum, etc., and various surface treatments such as silicone such as hydrogen silicone, cyclic hydrogen silicone, or other silane or titanium coupling agents Inorganic powder such as powder treated with an agent to make it hydrophobic or hydrophilic; Starch, cellulose, nylon powder, polyethylene powder, polymethyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, Polyester powder, benzoguanamine resin powder, polyethylene terephthalate/polymethyl methacrylate laminate powder, polyethylene terephthalate/aluminum/epoxy laminate powder, etc., urethane powder, silicone powder, Teflon (registered trademark) powder, etc. Organic powders of various sizes and shapes Preferable examples include solid and surface-treated powders and organic-inorganic composite powders.

Examples of inorganic salts include sodium chloride-containing salts such as table salt, common salt, rock salt, sea salt, and natural salt; potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, ammonium chloride; sodium sulfate, aluminum sulfate, Aluminum/potassium sulfate (alum), aluminum/ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, iron sulfate, copper sulfate; sodium phosphates such as 1Na, 2Na, and 3Na phosphate, phosphoric acid Potassiums, calcium phosphates, and magnesium phosphates are preferred.

UV absorbers include para-aminobenzoic acid, para-aminobenzoic acid monoglycerol ester, N,N-dipropoxy para-aminobenzoic acid ethyl ester, N,N-diethoxy para-aminobenzoic acid ethyl ester, N,N-dimethyl para-aminobenzoic acid ethyl ester. Benzoic acid-based UV absorbers such as esters, N,N-dimethylpara-aminobenzoic acid butyl ester, N,N-dimethylpara-aminobenzoic acid methyl ester; anthranilic acid-based UV absorbers such as homomenthyl-N-acetylanthranilate; salicylic acid and salicylic acid UV absorbers such as sodium salts thereof, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate; octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl -2,5-diisopropylcinnamate, ethyl-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxy Cinnamate, 2-ethylhexyl-p-methoxycinnamate (octyl paramethoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate (cinoxate), cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β- cinnamic acid-based UV absorbers such as phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate (octocrine), glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate, ferulic acid and derivatives thereof; 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2- Hydroxy-4-methoxybenzophenone (oxybenzone-3), 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl- Benzophenones such as 4′-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone Non-based UV absorber; 3-(4'-methylbenzylidene)-d,l-camphor, 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy- 5-methylphenylbenzotriazole; 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole;2-(2'-hydroxy-5'-methylphenylbenzotriazole;dibenzalazine;dianisoylmethane; 5- (3,3-dimethyl-2-norbornylidene)-3-pentan-2-one; dibenzoylmethane derivatives such as 4-t-butylmethoxydibenzoylmethane; octyl triazone; urocanic acid such as urocanic acid and ethyl urocanate Derivatives; 2-(2'-hydroxy-5'-methylphenyl)benzotriazole, 1-(3,4-dimethoxyphenyl)-4,4-dimethyl-1,3-pentanedione, dimethoxybenzylidenedioxoimidazolidinepropion Preferable examples include hydantoin derivatives such as 2-ethylhexyl acid, phenylbenzimidasozole sulfonic acid, terephthalylidene dicamfursulfonic acid, drometrisol trisiloxane, methyl anthranilate, rutin and its derivatives, oryzanol and its derivatives. .

Antiperspirants include aluminum chlorohydroxy, aluminum chloride, zinc oxide, zinc paraphenolsulfonate, and the like.

Cooling agents include menthol and methyl salicylate.

Examples of astringents include citric acid, tartaric acid, lactic acid, aluminum/potassium sulfate, and tannic acid.

Fragrances include acetylcedrene, amyl cinnamaldehyde, allyl amyl glycolate, β-ionone, iso-e-super, isobutylquinoline, iris oil, iron, indole, ylang-ylang oil, undecanal, undecenal, γ-undecenal, Estragole, eugenol, oakmoss, opoponax resinoid, orange oil, eugenol, aurantiol, galacsolid, carvacrol, L-carvone, camphor, cannon, carrot seed oil, clove oil, methyl cinnamate, geraniol, geranyl nitrile , isobornyl acetate, geranyl acetate, dimethylbenzyl carbyl acetate, styraryl acetate, cedryl acetate, terpinel acetate, pt-butylcyclohexyl acetate, betiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santa roll, cyclamenaldehyde, cyclopentadecanolide, methyl dihydrojasmonate, dihydromyrcenol, jasmine absolute, jasmine lactone, cis-jasmon, citral, citronenol, citronellal, cinnamon bark oil, 1,8-cineol, cinnamaldehyde, Styrax resinoid, cedarwood oil, cedren, cedrol, celery seed oil, thyme oil, damascone, damascenone, thymol, tuberose absolute, decanal, decalactone, terpineol, γ-terpinene, tripral, nerol, nonanal, 2,6-nonadienol, nonalactone , patchouli alcohol, vanilla absolute, vanillin, basil oil, patchouli oil, hydroxycitronellal, α-pinene, piperitone, phenethyl alcohol, phenylacetaldehyde, petitgrain oil, hexylcinnamaldehyde, cis-3-hexenol, peruvian balsam, vetiver oil , vetiverol, peppermint oil, pepper oil, heliotropine, bergamot oil, benzyl benzoate, borneol, myresinoid, musk ketone, methylnonylacetaldehyde, γ-methylionone, menthol, L-menthol, L-mentone, eucalyptus oil, β-ionone, Synthetic and natural fragrances such as lime oil, lavender oil, D-limonene, linalool, lilal, lilial, lemon oil, rose absolute, rose oxide, rose oil, rosemary oil, and various essential oils Preferable ones include raw materials and various perfume preparations.

Pigments, colorants, and dyes include Brown No. 201, Black No. 401, Purple No. 201, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 202, Blue No. 203, Blue No. 204, and Blue. No. 205, Blue No. 403, Blue No. 404, Green No. 201, Green No. 202, Green No. 204, Green No. 205, Green No. 3, Green No. 401, Green No. 402, Red No. 102, Red No. 104-1, Red 105-1, Red No. 106, Red No. 2, Red No. 201, Red No. 202, Red No. 203, Red No. 204, Red No. 205, Red No. 206, Red No. 207, Red No. 208, Red No. 213, Red 214, Red 215, Red 218, Red 219, Red 220, Red 221, Red 223, Red 225, Red 226, Red 227, Red 228, Red 230-1, Red 230-2, Red No. 231, Red No. 232, Red No. 3, Red No. 401, Red No. 404, Red No. 405, Red No. 501, Red No. 502, Red No. 503, Red No. 504, Red No. 505, Red 506, Orange 201, Orange 203, Orange 204, Orange 205, Orange 206, Orange 207, Orange 401, Orange 402, Orange 403, Yellow 201, Yellow 202-1, Yellow 202-2, yellow 203, yellow 204, yellow 205, yellow 4, yellow 401, yellow 402, yellow 403-1, yellow 404, yellow 405, yellow 406, yellow 407 , Yellow No. 5 and other legal dyes; Acid Red 14 and other acid dyes; Arianor Sienna Brown, Arianor Madder Red, Arianor Steel Blue, Arianor Straw Yellow and other basic dyes; HC Yellow 2, HC Yellow 5, HC Red 3, Nitro dyes such as 4-hydroxypropylamino-3-nitrophenol, N,N'-bis(2-hydroxyethyl)-2-nitro-p-phenylenediamine, HC Blue 2, Basic Blue 26; disperse dyes; astaxanthin, Anthraquinones such as alizarin, anthocyanidin, β-carotene, catenal, capsanthin, chalcone, calsamin, quercetin, crocin, chlorophyll, curcumin, cochineal, naphthoquinones such as shikonin, bixin, flavones, betacyanidin, henna, hemoglobin, lycopene, Natural colors such as riboflavin and rutin Elements/dyes; p-phenylenediamine, toluene-2,5-diamine, o-, m-, or p-aminophenol, m-phenylenediamine, 5-amino-2-methylphenol, resorcinol, 1-naphthol, 2 , 6-diaminopyridine and its salts, oxidation dye intermediates and couplers; autoxidation dyes such as indoline; and dihydroxyacetone.

[Method for producing composition]
The composition of the present invention can be produced, for example, by mixing and stirring at least one lipid peptide compound, water and, if desired, other ingredients while heating, and then allowing the mixture to stand and cool.

[Method for increasing the fluidization of the lipid structure of the skin and the use of a skin application to increase the fluidization of the lipid structure of the skin]
The present invention is also directed to a method of enhancing the fluidization of the lipid structure of the skin, characterized by applying to the skin a composition containing the aforementioned lipid peptide-type compound.
The present invention is further directed to the use of skin coatings to enhance fluidization of the lipid structure of the skin. The skin application consists of a composition containing the aforementioned lipid peptide-type compound.
The dosage form of the skin application agent is arbitrary, and for example, dosage forms applied to conventional cosmetics or external skin preparations: oil-in-water (O/W) type, water-in-oil (W/O) type, W/O/ Emulsified type such as W type, O/W/O type, oily, solid, liquid, kneaded, stick, volatile oil, powder, jelly, gel, paste, emulsified polymer type, sheet, Mist type, spray type and the like can be mentioned, but are not limited to these.
In addition, the product form of the above-mentioned skin preparation is also arbitrary, and for example, the product form applied to conventional cosmetics or external skin preparations: dispersion, milky lotion, cream, pack, spray, gel, sheet, etc. be able to.
Various components known to those skilled in the art can be blended into the above-mentioned skin application agent in accordance with the dosage form/product form in order to realize the dosage form/product form.

EXAMPLES Hereinafter, the present invention will be described in detail with reference to examples and test examples, but the present invention is not limited to these examples.

Reagents and the like used in Examples are as follows.
・ Pal-GH premix: Pal-GH (lipid peptide type compound: palmitoyl-glycine-histidine) 10%, polyoxyethylene (4) lauryl ether 8%, 1,2-hexanediol 4%, stearic acid 1%, Purified water 77%, Nissan Chemical Co., Ltd. Human three-dimensional cultured skin model: LabCyte EPI-MODEL 12 (human three-dimensional cultured epidermis, 12-well type), Japan Tissue Engineering Co., Ltd. Ascorbic acid 2-glucoside (hereinafter referred to as AA2G): Sigma Aldrich Co., Ltd. Arginine: Tokyo Chemical Industry Co., Ltd. Ammonium acetate: Fujifilm Wako Pure Chemical Industries, Ltd. Tetrabutylammonium bromide: Tokyo Chemical Industry Co., Ltd.

[Sample preparation method]
The Pal-GH premix was dissolved in purified water at 85° C. to obtain a uniform solution so that the desired concentration of Pal-GH was obtained. This was cooled to room temperature while being stirred with a mix rotor at a speed of 100 rpm.
For the samples used in the permeation test, an aqueous solution containing Pal-GH premix, ascorbic acid 2-glucoside, and arginine was dissolved at 85° C. in the proportions shown in Table 1 below. After that, using a mix rotor, the mixture was cooled to room temperature while being stirred at 100 rpm, and used as a sample for a permeation test. In the same procedure, an aqueous solution containing ascorbic acid 2-glucoside and arginine (not including Pal-GH) was dissolved at 85° C., cooled to room temperature, and used as a control sample for the permeation test.

[Permeation test]
Before conducting the permeation test, the human three-dimensional cultured skin model (LabCyte EPI-MODEL (Japan Tissue Engineering Co., Ltd.)) was washed twice with 2 mL of phosphate buffered saline (PBS), and the medium removed traces of
1 mL of PBS was placed as an acceptor phase in a multiple well plate for cell culture (Costar (registered trademark), 12 wells), and the human three-dimensional cultured skin model was placed therein and maintained at 32° C. for 1 hour.
500 μL of a permeation test sample was added to the donor compartment (cultured skin model cup). A skin permeation test was performed for a predetermined time (hereinafter referred to as test time).
After that, the skin model after the permeation test was processed according to the procedure for the test described below.

[Amount of active ingredient in human three-dimensional cultured skin model (Labcyte EPI-MODEL)]
For the active ingredient, ascorbic acid 2-glucoside, permeation tests were carried out using the samples of Examples 1 to 3 and the control example in Table 1 at test times of 1 hour, 3 hours, and 6 hours. After that, the surface of the stratum corneum (SC) of the human three-dimensional cultured skin model was washed twice with 0.5 mL of PBS.
After carefully separating the human three-dimensional cultured skin model from the donor compartment, it was extracted with a mixed solvent containing methanol:PBS (1:1 v/v) for 30 minutes. The extracted sample was then centrifuged at 15,000 xg for 10 minutes to obtain a supernatant.
The resulting supernatant was injected into HPLC and LC-MS columns, and the amount of permeation of ascorbic acid 2-glucoside and Pal-GH into the human three-dimensional cultured skin model was quantified under the following conditions. Experiments were performed at least in triplicate.

1. Permeation amount of ascorbic acid 2-glucoside (AA2G) (HPLC)
An HPLC system (Agilent Technologies) was configured with a system controller, pump, autosampler, column oven, UV detector (1260 Infinity II), and analysis software (ChemiStation).
Inertsil® ODS-4 (3 μm, 4.6×250 mm) (GL Sciences) was used as a column and maintained at 40°C.
The mobile phase was 20 mM ammonium acetate and 5 mM tetrabutylammonium bromide aqueous solution/acetonitrile = 4:1 v/v (premix, isocratic).
The flow rate was 0.7 mL/min, and the AA2G detection wavelength was 260 nm.
The results obtained are shown in FIG. In FIG. 1, A is after 1 hour, B is after 3 hours, and C is after 6 hours after adding the sample for permeation test to the donor compartment, the permeation amount of AA2G [μg /cm ² ]. Statistical significance was evaluated by Dunnett's post-hoc multiple comparison analysis after one-way analysis of variance (ANOVA). A difference of p<0.05 was considered statistically significant. All data are expressed as the mean±standard deviation (SD) of at least three independent experiments (*p<0.05, **p<0.01, ***p< 0.001, *****p<0.0001).

2. Permeation amount of Pal-GH (LC-MS)
Using an LC/MS system consisting of NexeraX2 (Shimadzu Corporation) and QExactive (Thermo Scientific, USA), the amphiphilic molecule Pal-GH (single ion mode, m/z = 449.3133 (±1)) was quantified.
Chromatographic separations were performed using an ACQUITY UPLC® BEH C18 (1.7 μm, 2.1×30 mm) (Waters) kept at 45°C.
A mobile phase gradient program using solvent A (0.1% formic acid-water) and solvent B (0.1% formic acid-acetonitrile) as mobile phases was run at a flow rate of 0.22 mL/min with the following gradient: applied in The gradient program started at 50% B and increased linearly to 98% B over 5 minutes, then held at 98% B for 3 minutes. The mobile phase B was then linearly decreased to the initial condition (50% B) within 0.1 min and then held at 50% B for 6.9 min to equilibrate. Total run time was 15.0 minutes.
A valve placed between the column and the mass spectrometer was switched to divert the column flow to waste during the first 1.5 minutes when unretained salts and impurities were eluting from the column. After 1.5 minutes, the valve was switched to direct flow to the mass spectrometer. After the analyte peak was recorded, the valve was turned back to waste and terminated after 4.5 minutes. The injection volume of the supernatant was 1 μL.
Mass spectrometry was performed using an electrospray source at a capillary temperature of 280°C, a sheath gas flow rate of 40, an auxiliary gas flow rate of 5, an auxiliary gas heater temperature of 50°C, an auxiliary gas flow rate of 40, an S-lens level of 100, and an ion spray voltage of -3.5 kV. under the conditions of negative mode. Mass detection was performed by electrospray ionization (ESI) in negative ion full scan mode followed by Pal-GH (m/z=449.3133 (±1)).
In Figure 2, test time: 3-hour human three-dimensional cultured skin model samples (Pal-GH premix containing 0.05%, 0.1%, 0.5%), permeation amount of AA2G by the HPLC [μg /cm ² ] (horizontal axis) and the permeation amount of Pal-GH [μg/cm ² ] (vertical axis).

[Confirmation of self-organized structure in human three-dimensional cultured skin model (Labcyte EPI-MODEL) (microscopic observation)]
Bright-field and fluorescence images were acquired using an inverted fluorescence phase-contrast microscope BZ-9000 (Keyence Corporation) equipped with a 40x objective lens.
The permeability of the Pal-GH self-assembled structure to the human three-dimensional cultured skin model was determined by dropping a thioflavin T aqueous solution (0.25 w / w%) on the surface of the Labcyte EPI-MODEL after the skin permeation test, and covering it with a cover glass. This was confirmed by labeling by covering with
Using the samples of Example 3 and the control example in Table 1, test time: after conducting a permeation test at 3 hours, the surface of the stratum corneum (SC: stratum corneum) of the human three-dimensional cultured skin model was applied to 0.5 mL. Washed twice with PBS. After that, the human three-dimensional cultured skin model was carefully separated from the donor compartment and subjected to labeling with the Thioflavin T aqueous solution.
FIG. 3 shows the results of microscopic photographs after labeling with the Thioflavin T aqueous solution after the skin permeation test. In FIG. 3, A and B show control examples (not including Pal-GH), and C and D are examples using Example 3 (containing 0.5% Pal-GH premix) (A in FIG. 3 and C are bright field images, B and D are fluorescence images).

(Interpretation of experimental results)
Thioflavin T (Th T) is known to react with a self-assembled structure: β-sheet structure and emit fluorescence. Therefore, when the self-assembled structure exists, it can be expected to be fluorescently labeled with Thioflavin T.
After a 3-hour skin permeation test, the skin was labeled with an aqueous solution of Thioflavin T (0.25 w/w%). , confirming the presence of the labeled structures in the skin. This suggests that Pal-GH is incorporated into the skin model in aggregated form. On the other hand, no fluorescence was observed in the skin permeation test of the control example.
From these results, the presence of self-assembled bodies in the skin was confirmed.

[Raman measurement of human three-dimensional cultured skin model (Labcyte EPI-MODEL)]
The Raman measurement was performed using a microscopic laser Raman spectrometer LabRam ARAMIS (Horiba, Ltd.) using a 785 nm diode laser as an excitation source.
Using the samples of Example 3 and Control Example in Table 1, a permeation test was performed at a test time of 3 hours, after which the Pal-GH formulation was removed and the human three-dimensional cultured skin model was washed with deionized water. After that, the human three-dimensional cultured skin model was separated from the donor compartment and placed on a silicone rubber with a hole of 1 cm in diameter. After putting the silicone rubber into the dish, PBS was poured until the holes in the rubber were filled in order to prevent drying of the human three-dimensional cultured skin model.
Raman spectra were acquired in reflection mode with 256 scans in the range 1900-400 cm ⁻¹ using a 100× objective.
The results obtained are shown in FIG. In FIG. 4, A is the scattering ^intensity [a. u. ] (vertical axis), the lower spectrum is Example 3 (Pal-GH-containing sample), the upper spectrum is the control example, and B is 1082 cm ^-1 in each sample (control example, Example 3). The intensity ratio [I ₁₀₈₂ /I ₁₀₆₁ ] of the Raman peak at 1061 cm ⁻¹ is shown.

(Interpretation of test results)
By analyzing conformational changes of lipid hydrocarbons in the skin by Raman analysis, permeability changes can be estimated. The bands at 1082 cm ⁻¹ and 1061 cm ⁻¹ are attributed to the gauche structure and trans structure of the C—C stretch of hydrocarbons, respectively. The intensity ratio (I ₁₀₈₂ /I ₁₀₆₁ ) increases as the number of hydrocarbons having a gauche structure in the skin increases, and changes in this value suggest structural changes in lipids in the skin.
As shown in FIG. 4, in this test, it was confirmed that when the sample containing Pal-GH (Example 3) was applied to the skin, the intensity ratio (I ₁₀₈₂ /I ₁₀₆₁ ) increased. The results suggest that it induces

[Measurement of small-angle X-ray scattering of human three-dimensional cultured skin model (Labcyte EPI-MODEL)]
In order to measure changes in the human three-dimensional cultured skin model after the permeation test for a predetermined time, the samples of Example 3 and the control example in Table 1 were used, test times: 15 minutes, 30 minutes, 60 minutes, 120 minutes, At 180 minutes, small-angle X-ray scattering measurements were performed according to the following procedure and data were acquired.
Small-angle X-ray scattering (SAXS) measurements were performed using NANO Viewer (manufactured by Rigaku Corporation). The camera length was 287 mm and the X-ray wavelength was 1.54 Å. Scattered intensities were accumulated for 900 seconds at room temperature using a PILATUS 2K detector.
An acrylic plate (thickness 1.2 mm) spacer is sandwiched between Kapton (special registered trademark) films, a human three-dimensional cultured skin model (Labcyte EPI-MODEL) separated from the donor compartment is placed therein, and a sample (Example 3 Or the control example) was set in the cell, and the test was conducted with an elapsed time of 0 minutes.
The results obtained are shown in FIG. In FIG. 5, A is the control example, B is the scattering spectrum in Example 3 (containing 0.5% Pal-GH premix) (test time 15 minutes, 30 minutes, 60 minutes, 120 minutes, 180 minutes from the bottom of the graph ). In addition, C is the q [Å] (left vertical axis) in the peak derived from the lipid structure (see arrows in A and B) for the test time [minute] (horizontal axis), and the interdomain distance [Å] (right vertical axis ).

(Interpretation of test results)
As shown in FIG. 5, the peak position derived from the lipid structure was shifted in the sample containing Pal-GH (Example 3). This indicates that the lipid membrane was swollen. In addition, although the peak was shifted, the peak remained without disappearing as in the control example, suggesting that the lipid membrane can be maintained.
The Raman measurement described above can capture more minute changes than the SAXS measurement, and the results of these Raman and SAXS measurements show that the structure of the lipid membrane itself is maintained by the sample containing Pal-GH. However, it was possible to induce micro disturbances in lipids, that is, it was suggested that the mobility (fluidization) of lipid structures was enhanced.

Claims (10)

A composition that enhances fluidization of the lipid structure of the skin, comprising:
Characterized by containing a lipid peptide type compound in which a peptide portion formed by repeating at least two or more identical or different amino acids is bound to a lipid portion consisting of an aliphatic group having 10 to 24 carbon atoms. ,Composition. 2. The composition of claim 1, wherein the composition is a composition that promotes fluidization of multi-layered structures of intercellular lipids. 1 or 2, wherein the lipid peptide compound comprises at least one compound represented by the following formulas (1) to (3) or a pharmaceutically acceptable salt thereof: 2. The composition according to 2.

(In the formula, R ¹ represents an aliphatic group having 9 to 23 carbon atoms, R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain of 1 or 2 carbon atoms. wherein R ³ represents a —(CH ₂ ) _n —X group, n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or has 1 to 3 nitrogen atoms; represents the 5-membered ring group or 6-membered ring group obtained, or the condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁴ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁵ to R ⁷ each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁸ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁹ to R ¹² each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom. an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.) 4. The composition according to any one of claims 1 to 3, wherein the composition penetrates into the skin while the lipid peptide compound forms a self-assembled structure. 1. A method for enhancing fluidization of the lipid structure of the skin, comprising:
A composition containing a lipid-peptide compound in which a peptide portion formed by repeating at least two identical or different amino acids is bonded to a lipid portion consisting of an aliphatic group having 10 to 24 carbon atoms is applied to the skin. A method, characterized in that applying 6. The lipid peptide type compound according to claim 5, characterized in that it comprises at least one compound represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof. Method.

(In the formula, R ¹ represents an aliphatic group having 9 to 23 carbon atoms, R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain of 1 or 2 carbon atoms. wherein R ³ represents a —(CH ₂ ) _n —X group, n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or has 1 to 3 nitrogen atoms; represents the 5-membered ring group or 6-membered ring group obtained, or the condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁴ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁵ to R ⁷ each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁸ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁹ to R ¹² each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom. an alkyl group of 1 to 4, or a —(CH ₂ ) _n —X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a —CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5-membered ring group or 6-membered ring group, or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.) 7. The method according to claim 5 or 6, wherein the composition penetrates into the skin while the lipid peptide compound forms a self-assembled structure. Use of a skin coating to enhance fluidization of the lipid structure of the skin, comprising:
The skin application agent contains a lipid peptide compound in which a peptide portion formed by repeating at least two identical or different amino acids is bound to a lipid portion composed of an aliphatic group having 10 to 24 carbon atoms. A use comprising the composition. 9. The lipid peptide compound according to claim 8, wherein the lipid peptide type compound comprises at least one compound represented by the following formulas (1) to (3) or a pharmaceutically acceptable salt thereof. use.

(In the formula, R ¹ represents an aliphatic group having 9 to 23 carbon atoms, R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain of 1 or 2 carbon atoms. wherein R ³ represents a —(CH ₂ ) _n —X group, n represents a number from 1 to 4, X is an amino group, a guanidino group, a —CONH ₂ group, or has 1 to 3 nitrogen atoms; represents the 5-membered ring group or 6-membered ring group obtained, or the condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.)

(In the formula, R ⁴ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁵ to R ⁷ each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom an alkyl group of 1 to 4, or a -(CH ₂ ) _n -X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a -CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5- or 6-membered ring group or a condensed heterocyclic group composed of a 5- and 6-membered ring.)

(In the formula, R ⁸ represents an aliphatic group having 9 to 23 carbon atoms, and R ⁹ to R ¹² each independently represent a hydrogen atom, a branched chain having 1 or 2 carbon atoms, and 1 carbon atom. an alkyl group of 1 to 4, or a -(CH ₂ ) _n -X group, where n is a number of 1 to 4, and X is an amino group, a guanidino group, a -CONH ₂ group, or 1 to 3 nitrogen atoms; represents a 5- or 6-membered ring group or a condensed heterocyclic group composed of a 5- and 6-membered ring.) 10. Use according to claim 8 or 9, characterized in that the composition penetrates into the skin with the lipid peptide compound forming a self-assembled structure.

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