dispersion and hydrogel formation method

专利摘要:
DISPERSION AND METHOD FOR THE FORMATION OF HYDROGEL An object is to provide a dispersion that contains a type of efficient lipid peptide compound such as a low molecular weight gelling agent, such as lipid dipeptide and a lipid tripeptide, and a dissolution accelerator capable of dissolving the peptide-type compound at a lower temperature and more easily. It is also an objective to provide a dispersion that can form a hydrogel using a simpler method and under a milder condition (low temperature) and from which a gel can be obtained in the form of a gel having a high thermal stability, and provide a method for forming the gel. A dispersion comprising: a peptide-type compound of lipids in which a peptide moiety formed by repeating at least two or more identical or different amino acids is attached to a lipid moiety that includes a C10-24 aliphatic group; a dissolution accelerator having, in molecules thereof, a hydrophilic part and a hydrophobic part, the hydrophilic part which has a betaine structure; and water; and a method for producing a hydrogel using the dispersion.
公开号:BR112016000274B1
申请号:R112016000274-1
申请日:2014-07-03
公开日:2021-01-05
发明作者:Takayuki Imoto
申请人:Nissan Chemical Industries, Ltd.；
IPC主号:

专利说明:

TECHNICAL FIELD
[0001] The present invention relates to a dispersion containing a low-molecular weight peptide-type compound useful as a thickener or a gel, and a method for forming a hydrogel through the dispersion. TECHNICAL STATUS
[0002] A hydrogel contains water as a solvent and is thus useful as a gel having a high biocompatibility. Such a hydrogel is used in various fields such as applications for commodities, such as paper diapers, cosmetics and aromatics.
[0003] Examples of a conventional hydrogel include polymeric gels formed through such steps that polymer chains are cross-linked to form a three-dimensional lattice structure, and that a non-covalent bond is formed between the three-dimensional lattice structure and the solvent such as water , as soon as the three-dimensional network structure swells to form a polymer gel. Many studies for the physical properties of the polymer gel and many developments of the polymer gel applications have been carried out with respect to natural polymeric gels formed from polysaccharide such as agarose and protein, and synthetic polymeric gels in which the polymer chains are cross-linked. with each other through a chemical covalent bond, such as an acrylamide gel. Recently, in addition to the gels above, containing polymer compounds, hydrogels formed by the self-assembly of an organic compound having a relatively low molecular weight and several hydrogels have been found.
[0004] The formation of the gel by self-assembly of a low molecular weight compound has been elucidated to occur through the following steps: In a substances (low molecular weight compounds) group in a random state at first, the molecules of the substances associate spontaneously, while they are having directionality for, for example, a non-covalent intermolecular interaction between the molecules of the substances under a suitable external condition (in medium) in order to form a macro assembly molecule: and plural macro molecules of sets forming a network and the network waves, with a surrounding solvent to form a gel. Examples of a driving force for this molecule association (self-assembli) include a force by an action of a hydrogen bond with a relatively weak bonding force, and a force by a van der Waals interaction (non-hydrogen bond), with an even weaker bonding strength than that of hydrogen bonding.
[0005] Many of the low molecular weight gelling agents that have been described are an amphipathic compound having a combination of a hydrophobic moiety with a long chain alkyl group and a hydrophilic moiety. Its examples include an amphipathic compound in which the hydrophilic moiety is an amino acid [Non-Patent Document 1], an amphipathic compound in which the hydrophilic moiety is a peptide [Patent Documents 1 and 2], an amphipathic compound in which hydrophilic moiety is a monosaccharide or a polysaccharide [Non-Patent Documents 2 and 3], and an amphipathic compound in which the hydrophilic moiety is a polyol [Non-Patent Document 4]. In addition, there has also been disclosed a low molecular weight gelling using such a tendency that a valine-based peptide easily carries a β- leaf structure [Non-Patent Document 5]. Said low molecular weight hydrogelifier can form a hydrogel by a method including: heating and stirring the hydrogelifier and water as the solvent under a temperature condition of about 100 ° C ° to dissolve and disperse the gel in water; and leaving the resulting solution to stand at room temperature. State of the art
[0006] Patent Documents Patent Document 1: International Publication No. WO 2009/005151 Patent Document 2: International Publication No. WO 2009/005152
[0007] Non-patent documents Non-patent document 1: Suzuki, Masahiro. Iumoto, Mariko. Mutsumi, Shirai. Hirofusa, Hanabusa, Kenji. Chemistri Letters, 33 (11), 1496-1497 Document 2 Non-patent: Jong Hwa Jung, Georeg John, Mitsutosish Mausda, Kaname Ioshida, Seiji Shinnkai, and Toshimi Shimizu Langumir 2001, 17, 7229- 7232 Non-patent document: I Hamachi, S. Kiionaka, S. Shinkai, Tetrahedron Lett, 2001, 42, 6141. I. Hamachi, S. Kiionaka, S. Shinaki, Chem .. Commun., 2000, 1281 Document 4 Non-patent: Masahiro Suzuki, Sanae Owa, Hirofusa Shirai and Kenji Hanabusa, Tetrahedron 2007 63 7302-7308 Non-patent Document 5: Ioko Matsuzawa, Katsuiuki Ueki, Masaru Ioshida, Nobuiuki Tamaoki, Tohru Nakamura, Hideki Sakai, and Masahiko Abe, Adv. Funct. Mater. 2007, 17, 1507-1514 SUMMARY OF THE INVENTION Problem to be solved by the Invention
[0008] It is an object of the present invention to provide a dispersion containing a type of lipid peptide compound useful as a low molecular weight gelling agent, such as lipid dipeptide and a lipid tripeptide, and a dissolution accelerator capable of dissolving the peptide type compound lipid at a lower temperature and more easily.
[0009] It is also an object of the present invention to provide a dispersion that can form a hydrogel through a simpler method and under a milder condition (low temperature) and from which a gel can be obtained in the form of a gel having high thermal stability, and provide a method for forming the gel. Means to Solve Problems
[0010] As a result of assiduous research which aims to overcome these disadvantages, the inventors of the present invention have found that a lipid peptide-type compound containing a low molecular weight lipid peptide or a pharmaceutically usable salt thereof exhibits a high solubility and high dispersibility in relation to those in a solvent, including a dissolution accelerator having, in molecules thereof, a hydrophilic portion and a hydrophobic portion in a condition of a temperature lower than the temperature in the case of a peptide-type compound conventional lipid, and forms a suitable dispersion as a premixed raw material for a gel or thickening agent for an antifreeze fluid.
[0011] The inventors of the present invention have also found that the addition of a polymer emulsifier to the dispersion in which the lipid peptide type compound is dissolved in the solvent, by preparing a gel, using the dispersion, even when the heated gelling dispersion is subjected to stirring-cooling, a gel can be formed appropriately, and the dispersion is useful as a premix for a gel applicable to cosmetics or quasi-drugs [classification used only in Japan]. The inventors of the present invention have further found that through the addition of a heat resistance enhancer to the dispersion, a high thermal stability can be transmitted to the gel obtained using the dispersion, and have completed the present invention.
[0012] The inventors of the present invention have further found that, using a dissolution accelerator, a satisfactory gel can be formed even when reducing the amount of addition of the peptide-type compound required for gelation and containing a low-peptide of molecular weight lipids or a pharmaceutically usable salt thereof.
[0013] Specifically, the present invention relates, according to a first aspect, a dispersion comprising: a peptide-type compound in which a peptide moiety formed by repeating at least two or more identical or different amino acids is attached to a lipid moiety including a C10-24 aliphatic group; a dissolution accelerator having, in molecules thereof, a hydrophilic part and a hydrophobic part, the hydrophilic part which has a betaine structure; and water.
[0014] The present invention relates, according to a second aspect, to the dispersion according to the first aspect, characterized in that the peptide-type compound of lipid contains at least one of the compounds of Formula (1) with the formula ( 3) and their pharmaceutically usable salts of the compounds:
(where R1 is a C9-23 aliphatic group; R2 represents a hydrogen atom or a C1-4 alkyl group optionally having a C1-2 chain branch; R3 represents a - (CH2) nX group; n is a number from 1 to 4; and X is an amino group, a guanidino group, a -CONH2 group, or a 5-membered ring optionally having 1 to 3 nitrogen atom (s), a 6-membered ring optionally having 1 to 3 nitrogen atoms (s), or a fused heterocyclic ring composed of a 5-membered ring and a 6-membered ring optionally having 1 to 3 nitrogen atom (s)),
(where R4 is a C9-23 aliphatic group; R5 to R7 are each, independently, a hydrogen atom, a C1-4 alkyl group optionally having a C 1-2 chain branch, or a - group (CH2 group ) nX; n is a number from 1 to 4; X is an amino group, a guanidino group, a -CONH2 group, or a 5-membered ring optionally having 1 to 3 nitrogen atom (s), a 6-membered ring optionally having 1 to 3 nitrogen atoms (s), or a fused heterocyclic ring composed of a 5-membered ring and a 6-membered ring optionally having 1 to 3 nitrogen atom (s)),
and (where R8 is a C9-23 aliphatic group; R9 to R12 are each independently a hydrogen atom, a C1-4 alkyl group optionally having a C 1-2 chain branch, or a - ( group CH2) nX; n is a number from 1 to 4; X is an amino group, a guanidino group, a group - CONH2, or a 5-membered ring optionally having 1 to 3 nitrogen atom (s), a ring 6 members optionally having 1 to 3 nitrogen atoms (s), or a fused heterocyclic ring composed of a 5 member ring and a 6 member ring optionally having 1 to 3 nitrogen atoms (s)). whether, according to a third aspect, the dispersion according to the first aspect, or the second aspect, which further comprises a polyhydric alcohol.
[0015] The present invention relates, according to a fourth aspect, the dispersion according to the third aspect, in which the dissolution accelerator is at least one selected from lauryl dimethyl amine betaine acetic acid, lauramidopropyl betaine, hydroxy lauryl sulfobetaine, stearyl betaine, and lysophosphatidylcholine.
[0016] The present invention relates, according to a fifth aspect, the dispersion according to any of the first aspect with the fourth aspect, further comprising a polymeric emulsifier, wherein the peptide-type lipid compound serves as a gelling agent .
[0017] The present invention relates, according to a sixth aspect, the dispersion according to the fifth aspect, wherein the dispersion is a premix for the preparation of a cosmetic or quasi-drug.
[0018] The present invention relates, according to a seventh aspect, the dispersion according to any of the first aspect with the fourth aspect, wherein the dispersion is used as a thickener for an antifreeze fluid.
[0019] The present invention relates, according to an eighth aspect, the dispersion according to the fifth or sixth aspect, in which the polymeric emulsifier is at least one polymer compound selected from the group consisting of a graft polymer compound in which a hydrophobic portion is grafted to a hydrophilic backbone and a block polymeric compound that contains a hydrophobic structural unit and a hydrophilic structural unit.
[0020] The present invention relates, according to a ninth aspect, the dispersion according to the eighth aspect, which further comprises a heat resistance enhancer.
[0021] The present invention relates, according to a tenth aspect, the dispersion according to the ninth aspect, wherein the heat resistance enhancer is at least one long chain alcohol selected from the group consisting of C10 -20 saturated and unsaturated higher alcohols or at least one higher fatty acid ester selected from the group consisting of saturated and unsaturated C10-20 higher fatty acid esters.
[0022] The present invention relates, according to an eleventh aspect, the dispersion according to the eleventh aspect, wherein the heat resistance enhancer is kethanol, myristyl alcohol or glyceryl monostearate.
[0023] The present invention relates, according to a twelfth aspect, to the dispersion according to the eighth aspect, in which the polymer compound is selected from the group consisting of a carboxymethyl cellulose and an acid ester alginic.
[0024] The present invention relates, according to a thirteenth aspect, to the dispersion according to the twelfth aspect, wherein the polymer compound is propylene glycol alginate.
[0025] The present invention relates, according to aspect XIV, a method for the production of a hydrogel, comprising the method: addition to the dispersion as described in any one of the fifth and sixth aspects, and the eighth aspect of the thirteenth aspect to water and heating the resulting mixture to a temperature that is room temperature or higher and lower than 100 ° C; and cooling the mixture, with stirring, until the temperature of the mixture reaches a lower temperature than the temperature on heating to form a gel.
[0026] The present invention relates, according to an aspect XV, a hydrogel formed using the dispersion, as described in any one of the fifth and sixth aspects, and the eighth aspect of the thirteenth aspect. Effects of the Invention
[0027] The dispersion of the present invention can be prepared by stirring the lipid-like peptide compound and a dissolution accelerator or the like under a relatively moderate temperature condition, such as at 80 ° C to dissolve and disperse the compound-lipid peptide type within a relatively short time. The dispersion of the present invention is a dispersion suitable as a premixed feedstock for a gel or a thickening agent for an antifreeze fluid.
[0028] A polymer emulsifier can be added to the dispersion of the present invention. This can provide an appropriate hydrogel without the formation of deposits of insoluble matter or in the preparation of a gel with the dispersion under a moderate temperature condition, such as at 80 ° C and even when the dispersion is stirred and cooled down. A polyhydric alcohol can be mixed in the dispersion of the present invention. This can provide an appropriate hydrogel, using an even lesser amount of the peptide-like lipid (gelling) compound. The dispersion is useful as a premix for a gel applicable to cosmetics or quasi-drugs.
[0029] In addition, a heat resistance enhancer can be added to the dispersion of the present invention. This can provide high thermal stability for the gel formed using the dispersion.
[0030] The peptide-like compound of the lipid contained in the dispersion of the present invention is a low molecular weight artificial compound composed only of a lipid and a peptide having an extremely high degree of safety. Phospholipids, biosurfactants, fatty acids or their salts, and surfactants that serve as the dissolution accelerator having, in molecules thereof, a hydrophilic portion and a hydrophobic portion, higher alcohols that serve as a heat-enhancing agent, polyhydric alcohols used for the dispersion solvent mixture, and other contents are additives applicable to food, cosmetics and medicines. That is, the dispersion of the present invention has a high degree of biological safety and, in particular, from the point of view of safety required for a base cell culture material, medical materials, cosmetic materials, or the like, the dispersion of the present invention is useful in the applications mentioned above.
[0031] In addition, the dispersion of the present invention can form a gel by water gelatinization without the use of a crosslinking agent or the like necessary during the formation of, for example, a type of synthetic polymer gel that has been described in detail. conventional way. Thus, any unreacted substance, such as an unreacted crosslinking agent, remains in the obtained hydrogel, for example. In addition, the peptide-type lipid compound contained in the dispersion can form a hydrogel only with the addition of a small amount of about 1% by mass, and a low load is applied to the environment and the body when the lipid composed of peptide type is incorporated into them.
[0032] The method for producing a hydrogel of the present invention can form a gel under a relatively mild condition such as at less than 100 ° C and even when the dispersion is heated with agitated gelling. Even when an additive for cosmetics or an additive for those drugs where heat influences are desired from these additives to be eliminated as much as possible, is added to the dispersion, the method of forming a hydrogel of the present invention can form a hydrogel without degenerating these. additions. The gel of the present invention can be obtained by adding a lesser amount of a gelling agent than for a conventional gel as described above, so that it can be mentioned that the gel of the present invention is a gel having a high degree of safety both in the body and the environment.
[0033] Furthermore, as described above, when a gel obtained from a lipid peptide which is a low molecular weight compound is used in an external environment, for example in the soil, the gel is easily decomposed by soil bacteria or similar, or, when the gel is used in an organism, the gel is easily decomposed by a metabolic enzyme, so that a low load is applied to the environment and the organism.
[0034] The gel of the present invention is a gel that is capable of being formed under a mild condition and with which the additives that can be influenced by heat, can be mixed. WAYS OF CONDUCTING THE INVENTION
[0035] Hereinafter, the present invention is described in detail, including the circumstances that led to the completion of the present invention.
[0036] A low gelling agent described in a conventional molecular weight form, for example, an ice cream containing as the hydrophilic portion, a peptide (a lipid peptide, in Patent Documents 1 and 2) shows poor solubility in a solvent, so that because it causes the gelling agent to gel a solvent, it is necessary that first, a desired solvent to be gelled is heated to an elevated temperature such as 100 ° C to dissolve and disperse the gelling agent in the solvent.
[0037] The lipid peptide above low molecular weight gelling is considered to be able to complete gel formation by forming a macro molecular assembly through a weak interaction (van der Waals interaction and the like) between the molecules and destruction such a molecular assembly makes it difficult to gel formation. Therefore, it is necessary for gel formation that a gelling dispersion prepared by heating the solvent at an elevated temperature while leaving the gelling dispersion cooled. When the gelling dispersion is stirred during cooling, gel formation cannot be produced.
[0038] According to such circumstances, the inventors of the present invention have discovered an object of providing a material capable of forming a gel under milder temperature conditions, for example, at a temperature below 100 ° C and capable of forming a gel even when the heated gelling dispersion is stirred during cooling of the dispersion. Then, for an object of this type, the inventors of the present invention studied a method for the formation of a gel by: dissolving and temporarily dispersing a peptide-type compound in a composition which accelerates the dissolution of the compound to prepare a solution (dispersion); and mixing the solution (dispersion), such as what is called a premixing of a gelling material in a solvent (such as water).
[0039] First, when the inventors of the present invention studied a dissolution accelerator having high solubility capable of dissolving a lipid peptide-type compound in a high concentration, in particular with a high degree of safety, through which the use of the accelerator of dissolution for quasi-drugs, cosmetics, and the like is acceptable, they found that a compound having, in its molecules, a hydrophilic moiety that has a betaine structure and a hydrophobic moiety is suitable for this purpose.
[0040] Subsequently, the inventors of the present invention having several times studied ways to allow the formation of gel, using the above premixture at a low temperature, with agitation, found that by mixing a polymeric emulsifier, such as an ester of alginic acid in the premix, the solubility and dispersibility of the premix and the strength of the gel when the premix is mixed in a solvent can be fixed, and by mixing with a heat-enhancing agent, such as a higher alcohol or a higher fatty acid ester in the premix, the heat resistance of the formed gel can be improved.
[0041] According to the circumstances mentioned above, the inventors of the present invention have completed the present invention. <Dispersion>
[0042] The dispersion of the present invention contains a mixed solution comprising a peptide-like lipid compound in which a peptide moiety formed by repeating at least two or more identical or different amino acids is attached to a lipid moiety that includes a C10 aliphatic group -24; a dissolution accelerator having, in molecules thereof, a hydrophilic portion having a betaine structure and a hydrophobic portion; and water. [Lipid-like peptide compound]
[0043] As the lipid peptide-type compound in the dispersion of the present invention, a compound (lipid peptide) of Formula (1) below to Formula (3) below, or a pharmaceutically usable salt thereof (a compound of low molecular weight having a lipid moiety which is a hydrophobic moiety and a peptide moiety which is a hydrophilic moiety) can be used.

[0044] In Formula (1), R1 is a C9-23 aliphatic group, preferably a linear C11-23 aliphatic group having, optionally, 0 to 2 unsaturated bonds.
[0045] Specific examples of the lipid moiety (acyl group) consisting of R1 and a carbonyl group adjacent to R1 include a lauroyl group, a dodecylcarbonyl group, a myristoyl group, a tetradecyl carbonyl group, a palmitoyl group, a margaroyl group , an oleoyl group, a elaidoyl group, a linoleoyl group, a stearoyl group, a vaccenoil group, n octadecyl carboxy group, an arachidoil group, an eicosylcarbonyl group, a behenoyl group, an erucanoil group, a docosylcarbonyl group, a lignoceroil group, and from a nervonoyl group and particularly preferred Examples of these include a lauroyl group, a myristoyl group, a palmitoyl group one, a margaroyl group, a stearoyl group, an oleoyl group, a elaidoyl group, and a behenoyl group.
[0046] In the general formula (1), R2 contained in the peptide moiety is a hydrogen atom or a C1-4 alkyl group optionally having a C1-2 chain branch.
[0047] The C1-4 alkyl group optionally having a C1-2 chain branch means an alkyl group in which the number of carbon atoms in the main structure is 1 to 4 and which may have a C1-2 chain branch, and specific examples of these include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl, isobutyl group, sec-butyl group, and tert-butyl group.
[0048] R2 preferably represents a hydrogen atom or a C1-3 alkyl group optionally having a C1 chain branch and more preferably a hydrogen atom.
The C1-3 alkyl group optionally having a branched C1 chain means an alkyl group in which the number of carbon atoms in the backbone is 1 to 3 and which may have a C1 chain branch, and specific examples of these include methyl group , ethyl, n-propyl group, isopropyl group, isobutyl group, and a sec-butyl group, and among them, the methyl group, isopropyl group, isobutyl group, and a sec-butyl group are preferred.
[0050] In the general formula (1), the symbol R3 represents a group - (CH2) n-X group. In the - (CH2) group nX, where n is a number from 1 to 4 and X is an amino group, a guanidino group, a -CONH2 group, or a 5-membered ring or a 6-membered ring optionally having 1 to 3 nitrogen atom (s), or a fused heterocyclic ring composed of a 5 membered ring and a 6 membered ring optionally having 1 to 3 nitrogen atom (s).
[0051] In the (CH2) nX group such as R3, X is preferably an amino group, a guanidino group, a carbamoyl group (a -CONH2 group), a pyrrole group, an imidazole group, a pyrazole group, or a group indole, and more preferably an imidazole group. In the - (CH2) nX group, n is preferably 1 or 2 and more preferably 1.
Accordingly, - (CH2) n- is preferably an aminomethyl group, a 2-aminoethyl group, a 3-aminopropyl group, a 4-aminobutyl group, a carbamoylmethyl group, a 2-carbamoylethyl group 3-carbamoylbutyl, a 2-guanidinoethyl group, a 3-guanidinobutyl group, a pyrrolemethyl group, a 4-imidazolemethil group, a pyrazolemethil group, or a 3-indolemethyl group, and more preferably a 4-aminobutyl group, a carbamoylmethyl group, a 2-carbamoylethyl group, a 3-guanidinobutyl group, a 4-imidazolemethyl group, or a 3-indolemethyl group, even more preferably a 4-imidazolemethyl group.
[0053] In the compound of Formula (1), such as a particularly preferred peptide lipid as the peptide-like lipid compound, compounds formed from the following lipid moieties and peptide moieties (assembled amino acid moiety) can be mentioned. Here, the short names for the amino acids are as follows: alanine (Ala); asparagine (ASN); glutamine (Gln); glycine (Gly); histidine (His); isoleucine (Ile); leucine (Leu); lysine (Lys); tryptophan (Trp); and valine (Val). Lauroil-Gli-His, Lauroil-Gly-Gln, Lauroil-Gly-Asn, Lauroil-Gly-Trp, Lauroil-Gly-Lis, lauroyl-Ala-His, Lauroil-Ala-Gln, lauroil-Ala-Asn, Lauroil- Ala-Trp, Ala-lauroyl-Lys; Miristoil-Gli-His, miristoil-Gly-Gln, miristoil-Gly-Asn, miristoil-Gly-Trp, miristoil-Gly-lis, myristoil-Ala-His, myristoil-Ala-Gln, myristoil-Ala-Asn, Miristoil- Ala-Trp, myristoyl-Ala-Lys; Palmitoil-Gli-His, Palmitoil-Gly-Gln, Palmitoil-Gly-Asn, Palmitoil-Gly-Trp, Palmitoil-Gly-Lis, palmitoil-Ala-His, Ala-palmitoil-Gln, palmitoil-Ala-Asn, Palmitoil- 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, Stearoil- Ala-Trp, estearoil-Ala-Lis.
[0054] Among them, the most preferred are Lauroil-Gly-His lauroyl-Ala-His-miristoil-Gly-His miristoil-Ala-His, Palmitoil-Gly-His palmitoil-Ala-His, estearoil-Gly-His and Stearoil -Ala-His.

[0055] In Formula (2), R4 is a C9-23 aliphatic group and preferred specific examples of the solvent include the same groups as defined with respect to R1 above.
[0056] In Formula (2), R5 to R7 are each independently a hydrogen atom, a C1-4 alkyl group optionally having a branched C1-2 chain, or a - (CH2) nX group and at least one of R5 to R7 is a - (CH2) nX group. n is a number from 1 to 4 and X is an amino group, a guanidino group, a -CONH2 group, or a 5-membered ring or a 6-membered ring optionally having 1 to 3 nitrogen atoms (s), or a fused ring heterocyclic ring, consisting of a 5-membered ring and a 6-membered ring optionally having 1 to 3 nitrogen atom (s). Here, specific preferred examples of R5 to R7 include the same groups as defined with respect to R2 and R3 above.
[0057] In the compound of Formula (2), such as a preferred lipid peptide, compounds formed from the following lipid moieties and peptide moieties (assembled amino acid moiety) can be mentioned. Myristoyl-Gly-Gly-His, miristoil-Gly-Gly-gln, miristoil-Gly-Gly-Asn, miristoil-Gly-Gly-Trp, myristoil-Gly-Gly-lys, myristoil-Gly-Gly-His, Miristoil-Gly-Gly-gly, myristoyl- Gly-Ala-Asn, myristoil-Gly-Ala-Trp, myristoil-Gly-Ala-Lis, Ala-myristoil-Gly-His, myristoil-Ala-Gly-Gln, myristoil-Ala- Gly-Asn, myristoil-Ala- Gly-Trp, Ala-myristoil-Gly-Lys, myristoil-Gly-His-Gly, myristoil-His-Gly-Gly, Gly-palmitoyl-Gly-His, palmitoil-Gly-Gly-Gly, Palmitoil-Gly-Gly-Gly Asn, Palmitoil-Gly-Gly-Trp, Palmitoil-Gly-Gly-Lys, Palmitoil-Gly-Ala-His, Palmitoil-Gly-Ala-Gly, Palmitoil-Gly-Aly-Asn, palmitoyl-Gly-Gly-Gly, Palmitoil-Gli-Ala-Lis, Ala-Palmitoil-Gly-His, palmitoil-Ala-Gly-Gln, palmitoil-Ala-Gly-Asn, palmitoil-Ala-Gly-Trp, Palmitoil- Ala-Gly-Lis, Palmitoil- Gly-His-Gly, palmitoyl-His-Gly-Gly.
[0058] Among them, the most preferred are Lauroil-Gly-Gly-His, myristoil-Gly-Gly-His, Palmitoil-Gly-Gly-His, Palmitoil-Gly-His-Gly, palmitoil-His-Gly-Gly, and estearoyl-Gly-Gly-His.

[0059] In Formula (3), the symbol R8 represents a C9-23 aliphatic group and preferred specific examples of the solvent include the same groups as defined with respect to R1 above.
[0060] In Formula (3), R9 to R12 are each, independently, a hydrogen atom, a C1-4 alkyl group optionally having a branched C1-2 chain, or a - (CH2) nX group and at minus one from R9 to R12 is a - (CH2) nX group. n is a number from 1 to 4 and X is an amino group, a guanidino group, a -CONH2 group, or a 5-membered ring or a 6-membered ring optionally having 1 to 3 nitrogen atoms (s), or a fused ring heterocyclic ring, consisting of a 5-membered ring and a 6-membered ring optionally having 1 to 3 nitrogen atom (s). Here, specific preferred examples of R9 to R12 include the same groups as defined with respect to R2 to R3 above.
Thus, in the compound of Formula (3), with a particularly preferred lipid peptide as the preferred peptide-like lipid compound, Lauroyl-Gly-Gly-Gly-His, myristoil-Gly-Gly-Gly can be mentioned -His, Palmitoil -Gli-Gly-Gly-His, Palmitoil-Gly-Gly-His-Gly, Palmitoyl-Gly-His-Gly-Gly, palmitoyl-His-Gly-Gly-Gly, and stearoyl-Gly-Gly-Gly Gli-His.
[0062] In the present invention, a mixture amount of the peptide-type lipid compound is, for example 0.01 wt% to 30 wt%, preferably 0.05 wt% to 10 wt%, and most preferably at 0.0.5% mass to 5% by mass, based on the total mass of the hydrogel obtained.
[0063] In the present invention, a mixture amount of the peptide-type lipid compound is, for example, 0. 1 wt% to 40 wt%, preferably 0.1 wt% to 30 wt%, and more preferably 0.1% by mass to 10% by mass, based on the total mass of the dispersion obtained.
The peptide-like lipid compound used in the present invention contains at least one of the compounds (lipid peptide) of formula (1) below Formula (3) below and their pharmaceutically usable salts thereof, and when the lipid type compound peptide is used as the hydrogelifier, these compounds can be used individually or in combination of two or more types thereof. [Accelerator dissolution]
[0065] The dissolution accelerator used for a dispersant in the present invention is a compound that has, in molecules thereof, a hydrophilic portion and a hydrophobic portion and the hydrophilic portion has a betaine structure (hereinafter it can be called a compound betaine-based).
[0066] Like the betaine-based compound above, the betaine-based compounds known as amphoteric surfactants can be used, for example, such as: N-alkyl-N, betaine amino acids N-dimethyl-betaine, such as laurildimethil aminoacetic acid (lauryl betaine); N-alkyl fatty acid amide, N-dimethyl betaine amino acids, such as betaine and cocoamidopropyl betaine lauramidopropyl; of the imidazoline type, such as sodium cocoanfoacetate and sodium lauroanfoacetate betaines; alkylsulfo betaines, such as hydroxy lauryl sulfobetaine and alkyl dimethyl taurine; sulfuric acid-type betaines, such as alkyl dimethyl amino ethanol sulfuric acid ester; phosphoric and acid-type betaines, such as alkyl phosphoric acid ester dimethyl amino ethanol.
[0067] Examples of the betaine-based compound include: glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), and phosphatidic acid; lizoglicerophospholipids such as lysophosphatidylcholine (lysolecithin), lysophosphatidylethanolamine, lizophosphatidilserine, lizophosphatidilinositol, lizophosphatidilglycerol and lisophosphatidic acid; sphingophospholipids, such as sphingomyelin; and hydrogenated products thereof. These phospholipids can be those derived from animals and plants such as soy beans and egg yolk or they can be synthesized by chemical or enzymatic processes.
[0068] Among betaine-based compounds, preferred examples include betaine laurildimethyl aminoacetic acid, lauramidopropyl betaine, sulfobetaine hydroxy lauryl, stearyl betaine, lysophosphatidylcholine (lysophosphatidylethanol, lysophosphatidylglycerol, lysophosphatidylglycerol, lysophosidylglycerol, lysophosphatidylglycerol, lysophosphatidylglycerol, lysophosphatidylglycerol, lysophosphatidylglycerol, lysophosphatidylglycerol. Other preferred examples are betaine laurildimethyl aminoacetic acid, lauramidopropyl betaine, hydroxy lauryl sulfobetaine, stearyl betaine, and lysophosphatidylcholine (lysolecithin).
[0069] They can be used alone or in combination of two or more.
[0070] In the present invention, a mixture amount of the dissolution accelerator is, for example 0.01 wt% to 1 wt% and more preferably 0.10 wt% to 0.50 wt%, based on total mass of the hydrogel obtained.
[0071] In the present invention, a mixture amount of the dissolution accelerator is, for example, 1 mass% to 30% mass, preferably 5% mass to 25% mass, based on the total mass of the dispersion obtained . [Polyhydric alcohol]
[0072] By mixing a polyhydric alcohol in the dispersion of the present invention, a suitable gel can be obtained even when a mixture amount of the peptide-like lipid compound serves as a gelling agent.
[0073] The polyhydric alcohol used for the dispersion of the present invention is at least one selected from the group consisting of 1,3-butylene glycol, propylene glycol, and glycerin. The polyhydric alcohol is preferably glycerin or 1,3-butanediol, preferably more than 1,3-butanediol.
[0074] Polyhydric alcohol is at least one of the aforementioned alcohols. These alcohols can be used alone or in combination of two or more.
[0075] In the present invention, a mixture amount of the polyhydric alcohol is, for example, 0.1 mass% to 10 mass% and more preferably 1% mass to 5% mass, based on the total mass of the obtained hydrogel.
[0076] In the present invention, a mixture amount of the polyhydric alcohol is, for example, 5% by mass to 30% by mass, preferably 15% by mass to 25% by mass, based on the total mass of the dispersion. obtained.
[0077] In the present invention, the dispersion containing the peptide-like lipid compound, the dissolution accelerator, and the polyhydric alcohol can be suitably used as a thickener of an antifreeze agent. [Emulsifying polymer]
[0078] The dispersion of the present invention that an emulsifier is added polymer can give a gel, even when the heated ice cream dispersion is stirred during the preparation of the gel. As the polymer emulsifier, at least one polymer compound selected from the group consisting of a graft polymer compound produced by grafting a hydrophobic group to a hydrophilic backbone and a block polymer compound containing a hydrophobic structural unit and a hydrophilic structural unit can be mixed in the dispersion of the present invention. [0039] Examples of the graft polymer compound produced by grafting a hydrophobic group to a hydrophilic backbone include xanthan gum, alginic acid esters, and cellulose derivatives.
[0079] Examples of the block polymer compound containing a hydrophobic structural unit and a hydrophilic structural unit include copolymers of alkyl methacrylates alkyl acrylates.
[0080] As the polymer compound, a compound selected from the group consisting of a carboxymethyl cellulose and an ester of alginic acid is preferred, and propylene glycol alginate is particularly preferred.
[0081] The polymer emulsifier used in the present invention is at least one selected from the group consisting of grafted polymer compounds and compounds of block polymer. These polymer compounds can be used alone or in combination of two or more.
[0082] In the present invention, a mixture amount of the polymeric emulsifier is, for example, 0.1 wt% to 5 wt% and more preferably 0.2 wt% to 0.5 wt%, based on total mass of the hydrogel obtained.
[0083] As the dispersion of the present invention, the dispersion containing the lipid peptide type compound as a gelling agent and containing, in addition to the dissolution accelerator and polyhydric alcohol, the polymeric emulsifier can be suitably used as a pre - mixture for the preparation of a cosmetic or quasi-drug, that is, as a premix material for the preparation of a gel used for a cosmetic or quasi-drug. In addition, in this dispersion (premix), a heat resistance enhancer and various additives known as additives for at least one of a cosmetic and quasi-drugs which are described below can also be mixed.
[0084] The premix can be produced by: adding a dissolution accelerator and a polyhydric alcohol with a peptide-type compound of lipids to stir the resulting mixture at room temperature or higher and lower than 100 ° C, preferably 50 ° C to 90 ° C, and more preferably 60 ° C to 90 ° C, for example 80 ° C; and if desired, the addition of a heat resistance enhancer and an additive for at least one of a cosmetic and quasi-drugs to the above mixture, to stir the resulting mixture. [Heat Resistance Enhancer]
[0085] As the heat resistance enhancer used for the dispersion of the present invention, a higher alcohol or a higher fatty acid ester can be added to the dispersion.
[0086] Examples of long-chain alcohol include higher saturated and unsaturated alcohols as follows: lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, beyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, dodecanol hexyl, dodecanol octyl stearyl alcohol -2- deciltetradecinol, cholesterol, phytosterols, sitosterol, lanosterol, cholesterol POE ether, and glycerin monostearyl ether (alcohol batil).
[0087] Among the upper alcohols above, one selected from the group consisting of C10-20 saturated and unsaturated upper alcohols is preferred. Preferred examples are lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, beenyl alcohol, oleyl alcohol, isostearyl alcohol, cholesterol, phytosterol, sitosterol, lanosterol, glycerin and monostearyl ether (bathyl alcohol). Even more preferred examples are lauryl alcohol, palmityl alcohol, myristyl alcohol and.
[0088] Ester oils such as diisobutyl adipate, 2-hexyldecyl, di-2-heptylundecyl adipate, N-alkylglycol monoisoestearate, isocetyl isostetate trimethylolpropane triisostearate, ethylene glycol: Examples of the higher fatty acid ester of higher fatty acids, as follows saturated and cetyl-2-ethylhexanoate di-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, ester gum octyldodecyl, oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl glycol tipprate, triethyl citrate, ethylhexyl 2-succinate, amyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, butyl stearate, diisopropyl sebacate, di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 2-ethylhexyl, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, 12-hydroxystearate cholesterol, acid ester of dipentaerythritol fat, isopropyl myristate, octyldodecyl myristate, 2-hexyldecyl myristate, myristyl myristate, dimethyloctanoate hexyldecyl, ethyl laurate, hexyl laurate, N-lauroyl-L-glutamic acid 2-octyl ester and d-estyl ester and d-ester esters diisostearyl malate; and glyceride oils such as acetoglyceride, triisooctanoate glyceride, glyceride triisostearate, triisopalmitate glyceride, tri-2-ethylhexanoate glyceride, glyceride monostearate, di-2-heptylundecanoate glyceride, trimiristate and glyceride.
[0089] Among the higher fatty acid esters, at least one selected from a group consisting of C10-20 saturated higher fatty acid esters is preferred. Preferred examples include N-alkylglycol mono-stearate and glyceride monostearate. Another preferred example is glyceride monostearate (glyceryl monostearate).
[0090] In the present invention, a mixture amount of the heat resistance enhancer is, for example 0.01 wt% to 0.30 wt%, preferably 0.02 wt% to 0.10 wt% , based on the total mass of the hydrogel obtained.
[0091] In the present invention, a mixture amount of the heat resistance enhancer is, for example, 0 to 2 wt% to 1.0 wt%, preferably 0.1 wt% to 0.5 wt%. mass, based on the total mass of the dispersion obtained.
[0092] The heat resistance improving agent used in the present invention is at least one type selected from the group of fatty acids above and these fatty acids can be used individually or in combination of two or more types thereof. [Other Additives]
[0093] In the composition of the pre-mixture, if necessary, an additive generally usable as an additive for cosmetic products and an additive for quasi- drugs can be mixed. Examples of an ingredient adding a biologically active substance, a functional substance, and the like, which are mixed in a preparation for external use for the skin, such as cosmetics and quasi-drugs include oil bases, moisturizers, touch enhancers, surfactants, polymers, thickening / gelling agents, solvents, propellants, antioxidants, agents, oxidizing agents, sterilizers, antimicrobial agents, bactericides, chelating agents, pH regulators, acids, alkalis, powder, inorganic salts, ultraviolet absorbers, bleaching agents, vitamins and their derivatives, reducing hair growth agents, blood circulation accelerators, stimulants, hormones, anti-wrinkle agents, anti-aging agents, tightening agents, cold sensing agents, hot sensing agents, wound healing promoters, irritant mitigators, analgesics , cell activators, plant / animal / microbe extracts, antipruritic to people, corneum releasing / dissolving agents, antiperspirants, soft drinks, astringent agents, enzymes, nucleic acids, perfumes, paints, dyes, dyes, pigments, anti-inflammatory agents, anti-inflammatory agents, anti-asthmatic agents, obstructive pulmonary disease agents anti-chronic, anti-allergic agents, immunomodulators, infectious anti-disease agents, and antifungal agents.
[0094] These adding ingredients are exemplified as follows. Preferred examples of the oil base include: (polyhydric) higher alcohols such as kethanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, ceto-stearyl alcohol, stearyl alcohol, arachyl alcohol, beenyl alcohol, jojoba alcohol, chimil alcohol, selachil alcohol, bathyl alcohol, hexildecanol, isostearyl alcohol, 2-octyldodecanol, and diol dimer; aralkyl alcohols and their derivatives, such as benzyl alcohol; higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docous acid - hexaenoic, eicosapentaenoic, iso hexadecanoic acid, long-chain branched fatty acids, dimeric acids, and hydrogenated dimeric acids, and an aluminum salt, a calcium salt, a magnesium salt, a zinc salt , a potassium salt, and a sodium salt above higher fatty acid salts which are metal soaps, and an above higher fatty acid amide which are nitrogen-containing derivatives above higher fatty acids; hydrocarbons such as liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, an α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, squalene derived from olive oil, squalene, petroleum jelly, and solid paraffin; waxes such as candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, Montana wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene waxes, and ethylene-propylene copolymer; vegetable oils and fats such as coconut oil, palm oil, palm seed oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea seed oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, walnut oil, rose hip oil, meadowfoam oil, persian 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, cocoa butter, shea butter, hydrogenated coconut oil, hydrogenated castor oil , jojoba oil, jojoba oil and hydrogenated oil; animal oils and fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, and turtle oil; animal waxes, such as spermaceti wax, lanolin, and orange glass oil; lanolin, such as liquid lanolin, reduced to lanolin, purified adsorption lanolin, lanolin acetate, acetylated lanolin, hydroxylated lanolin, polyoxyethylene lanolin, lanolin fatty acid, hard lanolin fatty acid, lanolin alcohol, acetylated lanolin alcohol , and an acetic acid (cetyl-lanolyl) ester; phospholipids, such as lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, sphingophospholipids, such as sphingomyelin, phosphatidic acid, and lysolecithin; phospholipid derivatives such as hydrogenated soy phospholipid, partially hydrogenated soy phospholipid, egg yolk phospholipid, and partially hydrogenated egg yolk phospholipid; sterols, such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, and cholic acid; sapogenin; saponin; sterol esters, such as cholesterol acetate, cholesteryl nonanoate, cholesterol, cholesterol stearate isostearate, cholesterol oleate, di (cholesteryl / beenyl / octyldodecyl) N-lauroyl-L-di (cholesteryl / octyldodecyl) N-lauroyl- Di (phitosteryl / beenyl / octyldodecyl) L-glutamate N-lauroyl-L-glutamate (diethyl N-lauroyl-L-glutamate), acylarcosine alkyl esters such as N-lauroylarcosinate isopropyl 12-cholesterol cholesteryl hydroxystearate macadamia oil fatty acid nut, phitosteril macadamia oil fatty acid nut, phitosteryl isostearate, lanolin fatty acid cholesteryl soft, lanolin hard cholesteryl fatty acid, cholesterol fatty acid long chain branched, and long chain α hydroxy-cholesteryl fatty acids; lipid complexes, such as phospholipid and cholesterol-phospholipid-phytosterol complex; mono-alcohol carboxylic acid esters, such as octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, cetyl palmitate, octyldodecyl, cetyl octanoate, hexyldecyl octanoate, isotridecyl isononyl, isotridyl, isonyl, isotonic , isostearyl neopentanoate, octyldodecyl neodecanoate, oleyl oleate, octyldodecyl oleate, octyldodecyl ricinoleate, lanolin octyldodecyl fatty acid, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrochloride oil, isoestearate hydrogenated acid, isoestearate hydrogenate isopropyl, isopropyl palmitate, octyl palmitate, isopropyl isostearate, isopropyl lanolin fatty acid, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate, diisopropyl adipate, dibutyloctilate dihydrate, succinate and dihydrate dihydrate triethyl; esters of oxy acids such as cetyl lactate, diisostearyl malate, and monoisoestearate hydrogenated castor oil; esters of polyhydric alcohol fatty acids such as glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, glyceryl diisostearate, tri (caprylate / caprinate), tri glyceryl (caprylate / caprinate / myristate / stearate), hydrophilicated colophony (colophony) hydrogenated ester gum), triglyceride rosin (ester gum), glyceryl beenate / eicosanedienoate, trimethylolpropane trioctanoate, trimethylolpropane triisostearate, neopentylglycol dioctanoate, neopentylglycol tipprinate, 2-butyl-propylene glycol dioleate, tetraoctanoate pentaerythritol, pentaerythritol hydrogenated rosin, triethilhexanoate ditrimethylolpropane, ditrimethylolpropane (isostearate / sebacate), pentaerythritol triethilhexanoate, dipentaerithritil (hydroxystearate / stearate / rosinate), diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 deca (erucate / isostearate / ric inoleate), diglyceryl oligoester of (hexildecanoic acid / sebacic acid), glycol distearate (ethylene glycol distearate), 3-methyl-1,5-pentanediol dineopentanoate, and 2,4-diethyl-1,5-pentanediol dineopentanoate; dimeric acid derivatives or diols such as diisopropyl dimer-dilinoleate, diisostearyl dimer-dilinoleate, di (isostearyl / phitosteryl) dimer-dilinoleate, (phitosteril / behenyl) dimer-dilinoleate, (phitosteril / isostyl-styrene / stearyl) / cetyl - dilinoleate, dilinoleyl-dilinoleate-dimer-dimer, dilisole-diiso-stearate-dimer, hydrogenated-dilinoleyl-rosin condenser, dimer-dilinoleate hydrogenated castor oil, hydroxyalkyl and dimer-dilinoleyl ether; fatty acid alkanolamides, such as coconut oil fatty acid monoethanolamide (cocoamide MEA), coconut oil fatty acid diethanolamide (cocoamide DEA), lauric acid monoethanolamide (MEA lauramide), lauric acid diethanolamide (lauramide DEA), monoisopropanolamide lauric acid (MIPA lauramide), palmitic acid monoethanolamide (paltamide MEA), palmitic acid diethanolamide (paltamide DEA), and coconut oil fatty acid methilethanolamide (cocamidemethil MEA); silicones, such as dimethicone (dimethylpolysiloxane), dimethicone having a high degree of polymerization (dimethyl polysiloxane with a high degree of polymerization), cyclomethicone (cyclic dimethylsiloxane), methylamethyl dimethylamine, phenylethyl dimethylamine, phenylethyl dimethicone, / dimethicone) copolymer, dimethicone, a crospolymer dimethicone, silicone resin, silicone rubber, modified with silicone amino, such as aminopropyl dimethicone and amodimethicone, modified from silicone cations, modified with silicone polyether, such as copolyol dimethicone, modified with silicone polyglycerin, sugar-modified silicone, acid-modified silicone carboxylic, phosphoric acid-modified silicone, sulfuric-acid-modified silicone, silicone-modified, silicone-modified fatty acid, alkyl-modified silicone modified amino acid silicone , modified-silicone peptide, modified with silicone fluorine, modified-cation and modified with silicone polyether, modified with amino and modified with silicone polyether, modified with alkyl and modified with silicone polyether, and of polysiloxane copolymer- oxyalkylene; and based on fluorine oil [Heat Resistance Enhancer]
[0095] As the heat resistance enhancer used for the dispersion of the present invention, a higher alcohol or a higher fatty acid ester can be added to the dispersion.
[0096] Examples of long-chain alcohol include higher saturated and unsaturated alcohols as follows: lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, beyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, dodecanol hexyl, dodecanol octyl stearyl alcohol -2- deciltetradeceth, cholesterol, phytosterols, sitosterol, lanosterol, cholesterol POE ether, and glycerin monostearyl ether (alcohol batil). Among the upper alcohols above, one selected from the group consisting of C10-20 saturated and unsaturated upper alcohols is preferred. Preferred examples are lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, beenyl alcohol, oleyl alcohol, isostearyl alcohol, cholesterol, phytosterol, sitosterol, lanosterol, glycerin and monostearyl ether (bathyl alcohol). Even more preferred examples are lauryl alcohol, palmityl alcohol and myristyl alcohol.
[0097] Examples of the higher fatty acid ester include unsaturated esters of higher fatty acids, as follows and saturated: ester oils, such as diisobutyl, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, N-alklyglycol monoisoestearate, trimethylolpropane triisostearate, isocetyl isostearate, 2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, octyldodecyl, oleate, oleate, oleate, oleate decyl oleate, neopentyl glycol tipprate, triethyl ethylene glycol-cetyl-2-ethylhexylate 2-ethylhexyl succinate, amyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, butyl stearate, diisopropyl sebacate, di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl, 2-heptylundecyl palmitate palmitate, 12-hydroxystearate cholesteryl, ester dipentaerythritol fatty acid, isopropyl myristate, octyldodecyl myristate, 2-hexyldecyl myristate, myristyl myristate, dimethyloctanoate hexyldecyl, ethyl laurate, hexyl laurate, 2-octyl dodecyl N-lauroyl-L-glutamic acid and L-glutamic acid diisostearyl malate; and glyceride oils such as acetoglyceride, triisooctanoate glyceride, glyceride triisostearate, triisopalmitate glyceride, tri-2-ethylhexanoate glyceride, glyceride monostearate, di-2-heptylundecanoate glyceride, trimiristate and glyceride.
[0098] Among the higher fatty acid esters, at least one selected from a group consisting of C10-20 saturated higher fatty acid esters is preferred. Preferred examples include N-monoisoestearate, alkylglycol and glyceride monostearate. Another preferred example is glyceride monostearate (glyceryl monostearate).
[0099] In the present invention, a mixture amount of the improved heat resistance is, for example 0.01 wt% to 0.30 wt%, preferably 0.02 wt% to 0.10 wt%, based on the total mass of the hydrogel obtained.
[00100] In the present invention, a mixture amount of the heat resistance enhancer is, for example, 0 to 2 mass% to 1.0 mass%, preferably 0.1 mass% to 0.5 mass% , based on the total mass of the dispersion obtained.
[00101] The heat-enhancing agent used in the present invention is at least one type selected from the group of fatty acids above and these fatty acids can be used individually or in combination of two or more types thereof. [Other additives]
[00102] In the composition of the premix, if necessary, an additive generally usable as an additive for cosmetic products and an additive for quasi-drugs can be mixed. Examples of an ingredient adding a biologically active substance, a functional substance, and the like, which are mixed in a preparation for external use for the skin, such as cosmetics and quasi-drugs include oil bases, moisturizers, touch enhancers, surfactants, polymers , thickening / gelling agents, solvents, propellants, antioxidants, agents, oxidizing agents, sterilizers, antimicrobe agents, bactericides, chelating agents, pH regulators, acids, alkalis, powder, inorganic salts, ultraviolet absorbers, bleaching agents, vitamins and their derivatives , hair growth reducing agents, blood circulation accelerators, stimulants, hormones, anti-wrinkle agents, anti-aging agents, tightening agents, cold sensing agents, hot sensing agents, wound healing promoters, irritant mitigators, analgesics, cell activators, plant / animal / microbe extracts, antipruritic a people, corneum releasing / dissolving agents, antiperspirants, soft drinks, astringent agents, enzymes, nucleic acids, perfumes, paints, dyes, dyes, pigments, anti-inflammatory agents, anti-inflammatory agents, anti-asthmatic agents, obstructive pulmonary disease agents anti-chronic, anti-allergic agents, immunomodulators, infectious anti-disease agents, and antifungal agents.
[00103] These adding ingredients are exemplified as follows.
[00104] Preferred examples of the oil base include: (polyhydric) higher alcohols such as kethanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, ceto-stearyl alcohol, stearyl alcohol, arachil alcohol, beyl alcohol, jojoba alcohol, chimil alcohol , selachil alcohol, bathyl alcohol, hexildecanol, isostearyl alcohol, 2-octyldodecanol, and diol dimer; aralkyl alcohols and their derivatives, such as benzyl alcohol; higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docous acid - hexaenoic, eicosapentaenoic, isohexadecanoic acid, anteiso-heneicosanoic acid, long chain branched fatty acids, dimeric acids, and hydrogenated dimeric acids, and an aluminum salt, a calcium salt, a magnesium salt, a zinc salt, a potassium salt, and a sodium salt above higher fatty acids that are metal soaps, and an above higher fatty acid amide that are derivatives containing nitrogen above higher fatty acids; hydrocarbons such as liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, an α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, squalene derived from olive oil, squalene, petroleum jelly, and solid paraffin; waxes such as candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, Montana wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene waxes, and ethylene-propylene copolymer; vegetable oils and fats such as coconut oil, palm oil, palm seed oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea seed oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, walnut oil, rose hip oil, meadowfoam oil, persian 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, cocoa butter, shea butter, hydrogenated coconut oil, hydrogenated castor oil , jojoba oil, jojoba oil and hydrogenated oil; animal oils and fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, and turtle oil; animal waxes, such as spermaceti wax, lanolin, and orange glass oil; lanolin, such as liquid lanolin, reduced to lanolin, purified adsorption lanolin, lanolin acetate, acetylated lanolin, hydroxylated lanolin, polyoxyethylene lanolin, lanolin fatty acid, hard lanolin fatty acid, lanolin alcohol, acetylated lanolin alcohol , and an acetic acid (cetyl-lanolyl) ester; phospholipids, such as lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, sphingophospholipids, such as sphingomyelin, phosphatidic acid, and lysolecithin; phospholipid derivatives such as hydrogenated soy phospholipid, partially hydrogenated soy phospholipid, egg yolk phospholipid, and partially hydrogenated egg yolk phospholipid; sterols, such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, and cholic acid; sapogenin; saponin; sterol esters, such as cholesterol acetate, cholesteryl nonanoate, cholesterol, cholesterol stearate isostearate, cholesterol oleate, di (cholesteryl / beenyl / octyldodecyl) N-lauroyl-L-di (cholesteryl / octyldodecyl) N-lauroyl- Di (phitosteryl / beenyl / octyldodecyl) L-glutamate N-lauroyl-L-glutamate (diethyl N-lauroyl-L-glutamate), acylarcosine alkyl esters such as N-lauroylarcosinate isopropyl 12-cholesterol cholesteryl hydroxystearate macadamia oil fatty acid nut, phitosteril macadamia oil fatty acid nut, phitosteryl isostearate, lanolin fatty acid cholesteryl soft, lanolin hard cholesteryl fatty acid, cholesterol fatty acid long chain branched, and long chain α hydroxy-cholesteryl fatty acids; lipid complexes, such as phospholipid and cholesterol-phospholipid-phytosterol complex; mono-alcohol carboxylic acid esters, such as octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, cetyl palmitate, octyldodecyl, cetyl octanoate, hexyldecyl octanoate, isotridecyl isononyl, isotridyl, isonyl, isotonic , isostearyl neopentanoate, octyldodecyl neodecanoate, oleyl oleate, octyldodecyl oleate, octyldodecyl ricinoleate, lanolin octyldodecyl fatty acid, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrochloride oil, isoestearate hydrogenated acid, isoestearate hydrogenate isopropyl, isopropyl palmitate, octyl palmitate, isopropyl isostearate, isopropyl lanolin fatty acid, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate, diisopropyl adipate, dibutyloctilate dihydrate, succinate and dihydrate dihydrate triethyl; esters of oxy acids such as cetyl lactate, diisostearyl malate, and monoisoestearate hydrogenated castor oil; esters of polyhydric alcohol fatty acids such as glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, glyceryl diisostearate, tri (caprylate / caprinate), tri glyceryl (caprylate / caprinate / myristate / stearate), hydrophilicated colophony (colophony) hydrogenated ester gum), triglyceride rosin (ester gum), glyceryl beenate / eicosanedienoate, trimethylolpropane trioctanoate, trimethylolpropane triisostearate, neopentylglycol dioctanoate, neopentylglycol tipprinate, 2-butyl-propylene glycol dioleate, tetraoctanoate pentaerythritol, pentaerythritol hydrogenated rosin, triethilhexanoate ditrimethylolpropane, ditrimethylolpropane (isostearate / sebacate), pentaerythritol triethilhexanoate, dipentaerithritil (hydroxystearate / stearate / rosinate), diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 deca (erucate / isostearate / ric inoleate), diglyceryl oligoester of (hexildecanoic acid / sebacic acid), glycol distearate (ethylene glycol distearate), 3-methyl-1,5-pentanediol dineopentanoate, and 2,4-diethyl-1,5-pentanediol dineopentanoate; dimeric acid derivatives or diols such as diisopropyl dimer-dilinoleate, diisostearyl dimer-dilinoleate, di (isostearyl / phitosteryl) dimer-dilinoleate, (phitosteril / behenyl) dimer-dilinoleate, (phitosteril / isostyl-styrene / stearyl) / cetyl - dilinoleate, dilinoleyl-dilinoleate-dimer-dimer, dilisole-diiso-stearate-dimer, hydrogenated-dilinoleyl-rosin condenser, dimer-dilinoleate hydrogenated castor oil, hydroxyalkyl and dimer-dilinoleyl ether; fatty acid alkanolamides, such as coconut oil fatty acid monoethanolamide (cocoamide MEA), coconut oil fatty acid diethanolamide (cocoamide DEA), lauric acid monoethanolamide (MEA lauramide), lauric acid diethanolamide (lauramide DEA), monoisopropanolamide lauric acid (MIPA lauramide), palmitic acid monoethanolamide (paltamide MEA), palmitic acid diethanolamide (paltamide DEA), and coconut oil fatty acid methilethanolamide (cocamidemethil MEA); silicones, such as dimethicone (dimethylpolysiloxane), dimethicone having a high degree of polymerization (dimethyl polysiloxane with a high degree of polymerization), cyclomethicone (cyclic dimethylsiloxane), methylamethyl dimethylamine, phenylethyl dimethylamine, phenylethyl dimethicone, / dimethicone) copolymer, dimethicone, a crospolymer dimethicone, silicone resin, silicone rubber, modified with silicone amino, such as aminopropyl dimethicone and amodimethicone, modified from silicone cations, modified with silicone polyether, such as copolyol dimethicone, modified with silicone polyglycerin, sugar-modified silicone, acid-modified silicone carboxylic, phosphoric acid-modified silicone, sulfuric-acid-modified silicone, silicone-modified, silicone-modified fatty acid, alkyl-modified silicone modified amino acid silicone , modified-silicone peptide, modified with silicone fluorine, modified-cation and modified with silicone polyether, modified with amino and modified with silicone polyether, modified with alkyl and modified with silicone polyether, and of polysiloxane copolymer- oxyalkylene; and fluorine based on petroleum solutions, such as perfluorodecane, perfluorooctane, and perfluoropolyether.
[00105] Preferred examples of moisturizer and touch enhancer include: polyols such as glycerin, 1,3-butylene glycol, propylene glycol, 3-methyl-1,3-butanediol, 1,3-propanediol, 2-methyl -1,3- propanediol, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, and ethylene glycol and propylene glycol-polymer copolymers of these polyols; alkyl glycol ethers, such as diethylene glycol monoethyl ether (ethoxydiglycol), monoethyl ethylene glycol ether, ethylene glycol monobutyl ether, diethylene glycol and dibutyl ether; water-soluble esters such as polyglyceryl-10 (eicosapentaenoate / tetradecane dienoate) and polyglyceryl-10 tetradecan ethyl dienoate; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, and maltitol; saccharides such as glucose, fructose, galactose, mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, trehalose, lactose, raffinose, gluconic acid, glucuronic acid, cyclodextrins (α-cyclodextrin, β-cyclodextrin, y-cyclodextrin, y-cyclodextrin , and modified cyclodextrin, such as maltosilated cyclodextrin and hydroxyalkylated cyclodextrin), β-glucan, chitin, chitosan, heparin and its derivatives, pectin, arabinogalactane, dextrin, dextran, glycogen, ethyl glucoside, polymers or polymers or copolymers and derivatives of these saccharides; hyaluronic acid and sodium hyaluronate; chondroitin sodium sulfate; mucoitin sulfuric acid, charonin sulfate, keratosulfate, and dermatan sulfate; Tremella fuciformis extracts and Tremella fuciformis polysaccharides; fucoidan; tuberous polysaccharides or natural polysaccharides; organic acids such as citric acid, tartaric acid, and lactic acid, and their salts; urea and its derivatives; 2-pyrrolidone-5-carboxylic acid and its salts, such as a sodium salt; amino acids, such as betaine (trimethylglycine), proline, hydroxyproline, alginine, lysine, serine, glycine, alanine, phenylalanine, tyrosine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cysteine, methionine, leucine, isoleucine, valine, tryptophan, histidine, and taurine, and salts of these amino acids; protein peptides, such as collagen, fish-derived collagen, atelocolagen, gelatin, elastin, peptide decomposed collagen, hydrolyzed collagen, hydrolyzed collagen-hydroxypropylammonium chloride, peptide decomposed elastin, peptide decomposed keratin, hydrolyzed keratin, hydrolyzed peptide decomposed, conchiolin decomposed peptide silk, hydrolyzed silk, sodium silk lauroyl hydrolyzate, decomposed soy protein peptides, decomposed wheat protein peptide, wheat protein hydrolyzate, decomposed casein peptide, and the acylated peptide, and derivatives of these peptides from protein; acylated peptides such as palmitoyl oligopeptide, palmitoyl pentaptide, and palmitoyl tetrapeptide; silanized peptides; a culture solution of lactic acid bacteria, yeast extract, eggshell membrane protein, cow mucin submaxillary gland, hipotaurine, sesame glycoside lignan, glutathione, albumin, and whey; choline chloride and phosphorylcholine; Extracted animal / vegetable components, such as placenta extract, elastin, collagen, aloe extract, hamamelis water, cucumber water sponge, chamomile extract, licorice extract, comfrey extract, silk extract, brown rose extract, Iarrow extract, eucalyptus extract, and Melilot extract, ceramides, such as natural ceramide (types 1, 2, 3, 4, 5, 6), hydroxyceramide, pseudo-ceramide, sphingoglycolipid and extracts containing ceramide or saccharide ceramide.
[00106] Preferred examples of the surfactant include anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, surfactants and polymers. Preferred examples of the surfactant are as follows. Preferred examples of the anionic surfactant include, for example, salts of fatty acids such as potassium laurate and potassium myristate; alkyl sulfates, such as sodium lauryl sulfate, triethanolamine lauryl sulfate, ammonium lauryl sulfate and; alkyl polyoxyethylene sulfates, such as sodium laureth sulfate and triethanolamine laureth sulfate; salts of acyl-N-methylamino acids, such as cocoylmethil sodium taurate, potassium cocoylmethil taurate, sodium lauroylmethil taurate, miristoilmethil sodium taurate, sodium lauroylmethyl alaninate, sodium lauroyl sarcosinate, lauroyl methylamine and triethylamine oxide sodium; salts of acylamino acids, such as cocoyl sodium glutamate, cocoyl glutamate triethanolamine, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium stearoyl glutamate, palmitoyl ditriethanolamine aspartate, and cocoyl alaninate triethanolamine; polyoxyethylene alkyl ethers acetates such as sodium laureth acetate; salts of succinic acid esters such as sodium lauroilmonoethanolamide succinate; fatty acid ethanol-carboxylates alkanolamide; acyl lactates; polyoxyethylene sulfates of aliphatic amines; fatty acid alkanolamide sulfates; fatty acid glyceride sulfates, such as hydrogenated coconut glycerin, sodium sulfate oil fatty acid salt; alkylbenzene polyoxyethylene sulfates; olefin sulfonates, such as sodium α-olefin-sulfonate; alkyl sulfosuccinates, such as disodium lauryl sulfosuccinate and sodium dioctyl sulfosuccinate; alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate, sodium monolauroyl polyoxyethylene monoethanolamide sulfosuccinate, and sodium polypropylene glycol lauryl sulfosuccinate; alkyl sulfonates such as sodium benzene and triethanolamine tetradecylbenzenesulfonate tetradecylbenzenesulfonate; alkylnaphthalenesulfonates; alkanesulfonates; salts of methyl esters of α-sulfo fatty acids; salts of acylisethionic acids; glycidyl alkyl ethers sulfonates; sulfo alkyl acetates; alkyl ether phosphates, such as sodium laureth phosphate, sodium dilaureth phosphate, sodium trilaureth phosphate, and sodium phosphate; alkyl monooleth phosphates, such as potassium lauryl phosphate; sodium caseinate; alkyl aryl ethers phosphates; amide fatty ether phosphates; phospholipids, such as phosphatidylglycerol, phosphatidylinositol and phosphatidic acid; silicone-based anionic surfactants, such as acid-modified carboxylic silicone, phosphoric acid-modified silicone, and sulfuric acid-modified silicone. Preferred examples of the nonionic surfactant include, for example, polyoxyethylene alkyl ethers with various numbers of additional polyoxyethylene molecules, such as the laureth group (polyoxyethylene lauryl ether), cetet group (polyoxyethylene cetyl ether), stearide group (polyoxyethylene stearyl ether ), beheneth group (polyoxyethylene behenyl ether), isostearate group (polyoxyethylene isostearyl ether), and octyl dodeceth group (polyoxyethylene octydodecyl ether); polyoxyethylene-alkylphenyl ethers; derivatives of castor oil and hydrogenated polyoxyethylene castor oil, such as hydrogenated castor oil, polyoxyethylene castor oil, hydrogenated polyoxyethylene castor oil monoisoestearate, castor oil polyoxyethylene hydrogenated mono-mono-hydroglycerate monohydroglycerate monohydrate diester, and hydrogenated polyoxyethylene castor oil maleate; polyoxyethylene phytosterol; polyoxyethylene cholesterol; polyoxyethylene cholestanol; polyoxyethylene lanolin; polyoxyethylene reduced lanolin; polyoxyethylene-polyoxypropylene alkyl ethers, such as polyoxyethylene-polyoxypropylene cetyl ether, polyoxyethylene-polyoxypropylene-2-deciltetradecyl ether, polyoxyethylene-polyoxypropylene, polyoxyethylene-polyoxypropylene-hydrogenated polyethylene ether; polyoxyethylene-polyoxypropylene glycol; (poly) glycols, such as polyoxypropylene glycerin PPG-9 diglyceryl; of glycerin fatty acids partial esters, such as glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, oleate, glycerin fatty acid ester of coconut oil, glycerin monoester of cotton seed fatty acid glyceryl oil , glyceryl monoerucate, sesquioleate, α glycerin ester, α 'pyroglutamic acid - oleic acid, and glycerin mono stearate malic acid; esters of polyglycerine fatty acids, such as polyglyceryl-2,3,4,5,6,8, or 10 stearate, polyglyceryl-2 tristearate, polyglyceryl-10 decastearate, polyglyceryl-2,3,4,5,6,8, or 10 polyglyceryl-2 diiso-stearate (diglyceryl diiso-stearate), polyglyceryl-3 diiso-stearate, 10-polyglyceryl diiso-stearate, polyglyceryl-2 triisostearate, polyglyceryl-2 tetraisostearate, polyglyceryl-10 decals 6.8, or 10 oleate, polyglyceryl-6 dioleate, polyglyceryl-2 trioleate, and polyglyceryl-10 decaoleate; ethylene glycol fatty acid ester, such as ethylene glycol monostearate; propylene fatty acid monoester glycol, such as propylene glycol monostearate; pentaerythritol partial fatty acid ester; sorbitol ester of partial fatty acid; maltitol partial fatty acid ester; maltitol ether; fatty acid sorbitan ester, such as sorbitan monooleate, sorbitan monoisearearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylate and diglycerol sorbitan penta-2-ethylate and diglycerol sorbitan penta-2-ethylate diglycerol and penta-2-ethylate diglycerol. - 2-ethilhexilate; saccharide derived from partial esters, such as fatty acid sucrose ester, methylglucoside fatty acid ester, trehalose and undecylate; alkyl glucoside, such as caprylyl glucoside; alkyl polyglycoside; lanolin alcohol; reduced lanolin; polyoxyethylene mono fatty acid and diester, such as polyoxyethylene distearate, polyoxyethylene diisoestearate, polyoxyethylene monooleate, polyoxyethylene and dioleate; polyoxyethylene glycol propylene fatty acid ester; polyoxyethylene glycerin fatty acid ester such as polyoxyethylene-polyoxyethylene monooleate, such as glycerin monostearate, polyoxyethylene glycerine mono-stearate mono-stearate, glycerin and polyoxyethylene triisostearate; polyoxyethylene sorbitan ester with fatty acid, such as polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, and polyoxyethylene sorbitan tetraoleate; polyoxyethylene sorbitol fatty acid ester such as polyoxyethylene sorbitol monolaurate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitol pentaoleate, sorbitol and polyoxyethylene monostearate; polyoxyethylene methylglucoside fatty acid ester; polyoxyethylene alkyl ester of ether fatty acid; polyoxyethylene and vegetable oils and fats, such as polyoxyethylene sorbitol beeswax; ethers, such as alkyl glyceryl-isostearyl glyceryl ether, chimil alcohol, selachil alcohol, and bathyl alcohol; alkyl ether-polyhydric alcohol; polyoxyethylene alkylamine; tetrapolioxiethilene / tetrapolioxypropylene-ethylenediamine condensates; nature-originated surfactants, such as saponin and soforolipid; polyoxyethylene fatty acid amide; fatty acid alkanolamides, such as coconut oil fatty acid monoethanolamide (cocoamide MEA), coconut oil fatty acid diethanolamide (cocoamide DEA), lauric acid monoethanolamide (MEA lauramide), lauric acid diethanolamide (lauramide DEA), monoisopropanolamide lauric acid (MIPA lauramide), palmitic acid monoethanolamide (MEA paltamide), palmitic acid diethanolamide (DEA paltamide), and coconut oil fatty acid methilethanolamide (MEA methyl cocamide); alkyldimethylamine oxides such as lauramine oxide, cocamine oxide, stearamine oxide, and behenamine oxide; alkyl ethoxy dimethyl amine oxides; polyoxyethylene alkyl mercaptans; polyether modified silicones, such as copolyol dimethicone; and non-ionic silicone-based, such as poly-siloxane-oxyalkylene copolymers, modified silicone polyglycerin, and modified silicone saccharides. Preferred examples of the cationic surfactant include: alkyltrimethylammonium chlorides, such as Berrentimium chloride, steartrimonium chloride, cetrimonium chloride, chloride and lauryltrimonium; bromides, such as steartrimonium alkyltrimethylammonium bromide; dialkyldimethylammonium chlorides such as disteardimonium chloride and dicocodimonium chloride; amidoamines of fatty acids, such as stearamidopropyl dimethylamine and diethylamine stearamidoethyl, and their salts; alkyletheramines such as stearoxypropyl dimethylamine, and quaternary salts or salts thereof; quaternary ammonium salts of amide-type fatty acids, such as long-chain fatty acid (12 to 31) aminopropylethildimethilammonium sulfate acetate and lanolin fatty acid sulfate aminopropylethildimethilammonium; polyoxyethylene alkylamines and their salts or quaternary salts thereof; alkylamine salts; guanidine fatty acid amide salt; alkyl ammonium salts; ether ammonium salts of alkyl trialkylene glycol; benzalkonium salts; benzethyl salts; pyridinium salts such as cetylpyridinium chloride; imidazolinium salts; alkyl isoquinoline salts; dialkyl morpholium salts; polyamine fatty acid derivatives; and silicone-based, such as cationic surfactants modified with silicone amino, such as amodimethicone and aminopropyl dimethicone, modified with silicone cations, modified with cation and modified with silicone polyether, and modified with amino and modified with silicone polyether . Preferred examples of the amphoteric surfactant include N-alkyl-N, betaine amino acids N-dimethyl lauryl betaine, such as betaine (laurildimethyl aminoacetic acid); N-alkyl fatty acid amide, N-dimethyl betaine amino acids, such as betaine and cocoamidopropyl betaine lauramidopropyl; of the imidazoline type, such as sodium cocoanfoacetate and sodium lauroanfoacetate betaines; alkyl sulfate alkyl betaines, such as dimethyl taurine; sulfuric acid-type betaines, such as alkyl dimethyl amino ethanol sulfuric acid ester; phosphoric acid type, such as phosphoric acid ester betaines ethanol alkyl dimethyl; phospholipids such as sphingophospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and, lysolecithin, hydrogenated soy phospholipid, partially hydrogenated phospholipid soybean oil, hydrogenated egg hydrolyzed phospholipid yolk, partially hydrogenated, partially hydrogenated hydroxide; and based on amphoteric silicone surfactants. Preferred examples of the polymer surfactant include polyvinyl alcohols, sodium alginate, starch derivatives, tragacanth gum, copolymers of alkyl acrylates or alkyl methacrylates, and various silicone based surfactants.
[00107] Preferred examples of the polymer, the thickening agent, and the gelling agent include: guar gum; locust bean gum; quince seeds; carrageenan; galactan; Arabic gum; tare gum; tamarind; furcellaran; karaia gum; sunset hibiscus; face gum; tragacanth gum; pectin; salts of pectic acid and as its sodium salt; alginic acid and its salts, such as a sodium salt; manana; rice, corn, potato, and wheat starches; xanthan gum; dextran; succinoglucan; curdlan; hyaluronic acid and its salts; xanthan gum; pullulan, gelan gum; chitin; chitosan; agar; brown seaweed extract; chondroitin salt sulfate; casein; collagen; gelatine; albumin; celluloses and their derivatives, such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and its salts, such as a sodium salt, methylhydroxypropylcellulose, sodium cellulose sulfate, cellulose dialkyl dimethylammonium sulfate , crystalline cellulose, and powdered cellulose; starch polymers, such as soluble starch, carboxymethyl starch, methylhydroxypropyl starch, starch and methyl; starch derivatives such as hydroxypropyltrimonium chloride starch, corn starch and aluminum octenilsuccinate; alginic acid derivatives such as sodium alginate and propylene glycol alginate ester; polyvinylpyrrolidone (PVP); polyvinyl alcohol (PVA); vinylpyrrolidone-vinyl alcohol copolymers; polyvinyl methyl ether; polyethylene glycol; polypropylene glycol; polyoxyethylene-polyoxypropylene copolymers; amphoteric methacrylate ester copolymers, such as (methacryloyloxyethylcarboxibetaine / alkyl methacrylate) and copolymer of (acrylates / stearyl acrylate / ethylamine oxide methacrylate) copolymer; (dimethicone / vinildimethicone) transverse polymers; (alkyl acrylate / diacetoneacrylamide) and AMP- copolymer (alkyl acrylate / diacetoneacrylamide) copolymer; depolyvinyl acetate partially saponified products; maleic acid polymers; vinylpyrrolidone-dialkylaminoalkyl methacrylate copolymers; acrylic resin alkanolamines; water-dispersible polyesters and polyesters; polyacrylamides; polyacrylate ester copolymers, such as ethyl polyacrylate; carboxyvinyl polymers; salts of polyacrylic acid and, as a sodium salt thereof; copolymers of acrylate-methacrylate esters esters; alkyl acrylates-alkyl methacrylates copolymers; celluloses, such as cationized polyquaternium-10; diallyldimethylammonium-acrylamide chloride copolymers, such as polyquaternium-7; diallyldimethylammonium chloride-acrylic acid copolymers, such as polyquaternium-22; copolymers of acrylamide chloride-acrylic acid-diallyldimethylammonium, such as polyquaternium-39; methacrylate esters copolymers of cationized acrylate esters; copolymers of alkyl methacrylates alkylated acrylates; cationized acrylamide-methacrylamide copolymers; acrylate-methacrylamidepropyltrimethylammonium acrylic methyl acid chloride copolymers, such as polyquaternium-47; methacryloyl choline ester chloride polymers; polysaccharides, such as cationized cationized oligosaccharides, cationized dextran; hydroxypropyltrimonyium chloride guar; polyethyleneimines; cation polymers; polymers of 2-methacryloyloxyethyl phosphorylcholine such as polyquaternium-51, and their copolymers with a methacrylate-butyl copolymer; polymer emulsions, such as an acrylic resin emulsion, a polyacrylate acetate emulsion, a polyacrylalkyl ester emulsion, a polyvinyl acetate resin emulsion, natural rubber latex and synthetic latex; nitrocelluloses; polyurethanes and various copolymers; several silicones; various silicone-based copolymers, such as an acrylic grafted copolymer with silicone; various fluorine-based polymers; 12-hydroxystearic acid and its salts; esters of fatty acids, such as dextrin dextrin palmitate and dextrin myristate; silicic anhydride and pyrogenic silicic acid (ultrafine particle silicic anhydride); magnesium aluminum silicate and sodium magnesium silicate; metal soaps; dialkylphosphoric metal acid salts; bentonite; hectorite; organic modified clay minerals; esters of sucrose fatty acids; and oligosaccharide fatty acid esters. Among the examples above, celluloses and their derivatives, alginic acid and its salts, polyvinyl alcohols, hyaluronic acid and its salts, and collagen are preferred.
[00108] Preferred examples of the solvent and the propellant include: lower alcohols, such as ethanol, 2-propanol (isopropyl alcohol), butanol and isobutyl alcohol; glycols such as propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, and isopentyl diol; glycolic ethers such as diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, triethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol ether ethylic ether ethanol ether monoethyl; glycol ether esters, such as ethylene glycol monoethyl ethyl ether, diethylene glycol monoethyl ether acetate, and propylene glycol monoethyl ethyl ether; glycol esters such as diethoxyethyl succinate and ethylene glycol; disuccinate Benzyl alcohol; benzyloxyethanol; propylene carbonate; dialkyl carbonate; acetone; ethyl acetate; N-methylpyrrolidone; toluene; and propellants, such as fluorocarbon, fron gas for the next generation, LPG, dimethyl ether, and carbon dioxide.
[00109] Preferred examples of the antioxidant include: tocopherol derivatives such as tocopherol (vitamin E) and tocopherol acetate; BHT and BHA; gallic acid derivatives such as propyl gallate; at least one of vitamin C (ascorbic acid) and its derivative; erythorbic acid and its derivatives; sulfites, such as sodium sulfite; hydrogensulfites such as sodium hydrogen sulfite; thiosulfates such as sodium thiosulfate; metabisulfites; thiotaurine and hipotaurine; thioglycerol, thiourea, and thioglycolic acid; and cysteine hydrochloride.
[00110] Preferred examples of the reducing agent include thioglycolic acid, cysteine and cysteamine.
[00111] Preferred examples of the oxidizing agent include hydrogen peroxide to water, ammonium persulfate, sodium bromate, and percarbonic acid.
[00112] Preferred examples of the sterilizer, the antimicrobe agent, the bactericide and include the acid and its salts or esters thereof, such as methylparaben, ethylparaben, hydroxybenzoic propylparaben, and butylparaben; salicylic acid; sodium benzoate; phenoxyethanol; isothiazolinone derivatives, such as methyl chloro isothiazolinone and methyl isothiazolinone; imidazolic urea; dehydroacetic acid and salts thereof; phenols; halogenated bisphenols such as triclosan; acid amides; quaternary ammonium salts; trichlorocarbanilide; zinc pyrithione; benzalkonium chloride; benzethoniumu chloride; sorbic acid, chlorhexidine; chlorhexidine glucanate; halocarban; hexachlorophene; hyquititiol; except for the above phenols, such as phenol, isopropylphenol, cresol, thymol, p-chlorophenol, phenylphenol, and sodium phenylphenate phenols; phenylethyl alcohol; photosensitive elements; antibacterial zeolite; and silver ions.
[00113] Preferred examples of the chelating agent include: (ethylenediaminetetraacetates edetates), such as EDTA, EDTA2Na, EDTA3Na, and EDTA4Na; hydroxyethylethylenediaminetriacetates such as HEDTA3Na; pentetates (diethylenetriaminepentaacetates); phosphonic acids such as phytic acid and etidronic acid, and their salts, such as a sodium salt; sodium oxalate; polyamino acids such as polyaspartic acid and glutamic acid; sodium polyphosphate, sodium metaphosphate, and phosphoric acid; sodium citrate and citric acid; alanine; dihydroxyethylglycine; gluconic acid; Ascorbic acid; succinic acid; and tartaric acid.
[00114] Preferred examples of pH adjuster, acid, and alkaline include 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-propanediol, arginine, sodium hydroxide, potassium hydroxide, ammonia water, guanidine carbonate, and ammonium carbonate.
[00115] Preferred examples of the powder include: inorganic powder having various sizes and shapes, such as mica, talc, kaolin, sericite, biotite, montmorillonite, kaolinite, ichthyola, muscovite, phlogopite, synthetic ichthyola, lepidolite, vermiculite, magnesium carbonate , calcium carbonate, aluminum silicate, barium silicate, potassium silicate, magnesium silicate, strontium silicate, a metal salt of tangstic acid, magnesium, zeolite, barium sulfate, calcium stew sulfate, calcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder, bentonite, smectite, clay, mud, metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, red iron oxide, yellow iron oxide, oxide black iron, ultramarine blue, Prussian blue, carbon black, titanium oxide, fine or ultrafine particles titanium oxide particle, zinc oxide, particles or ultrafine particles of fine zinc oxide, aluminum na, silica, smoked silica (ultrafine silicic anhydride particle), titanium mica, fish guanine scale, boron nitride, a photochromic pigment, synthetic fluorophlogopite, powder composed of fine particles, gold, and aluminum; inorganic powder that is powdered or hydrophobized hydrophilized by subjecting the above inorganic powder to a treatment using various surface treatment agents, such as silicone, such as hydrogen silicone and hydrogen cyclic silicone, another silane, or a silane titanium coupling; organic powder having various sizes and shapes, such as starch, cellulose, nylon powder, polyethylene powder, poly (methyl methacrylate) powder, polystyrene powder, powder of a styrene copolymer resin and acrylic acid, powder polyester, benzoguanamine powder resin, powder in which polyethylene terephthalate and poly (methyl methacrylate) are layered, powder in which polyethylene terephthalate, aluminum, and are layered in epoxy, urethane powder, silicone powder, and Teflon (registered trademark) powder, and the surface treated; and powder of organic-inorganic compound.
[00116] Preferred examples of inorganic salt include: sodium salts containing chloride such as a salt, a crude salt, a rock salt, a sea salt, and a natural salt; potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, mother water, zinc chloride, and ammonium chloride; sodium sulphate, aluminum sulphate, aluminum and potassium sulphate (alum), aluminum and ammonium sulphate, barium sulphate, calcium sulphate, potassium sulphate, magnesium sulphate, zinc sulphate, iron sulphate, copper sulphate and; and sodium phosphates, such as monosodium phosphate dihydrate, disodium hydrogen phosphate, trisodium phosphate, and potassium phosphates, calcium, magnesium phosphates and phosphates.
[00117] Preferred examples of the ultraviolet absorber include: benzoic acid based ultraviolet absorbers such as p-aminobenzoic acid, p-aminobenzoic acid, acid monoglycerin ester, N, N-dipropoxy-p-aminobenzoic acid ethyl ester N, N-dimethyl-p-aminobenzoic acid ethyl ester, N, N-diethoxy-p-aminobenzoic acid butyl ester, N, N-dimethyl-p-aminobenzoic acid, and N, N-dimethyl-p-aminobenzoic acid ester ethyl; anthranilic acid-based ultraviolet absorbers such as homomentyl-N-acetylanthranilate; ultraviolet absorbents based on salicylic acid such as salicylic acid and its sodium salt, amyl salicylate, menthyl salicylate, homomentyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanolphenyl salicylate; ultraviolet absorbents based on cinnamic acid such as octyl cinnamate, 4-isopropyl cinnamate acetate, methyl-2,5-diisopropyl cinnamate, 2,4-diisopropicinamate acetate, methyl-2,4-diisopropyl cinnamate, propyl p-methoxycinnamate, isopropyl p-methoxycinnamate, isoamyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate (octyl p-methoxycinnamate), 2-ethylethyl p-methoxycinnamate (cinoxate), cyclohexyl p-methoxycinnamate, α- acetate glyceryl cyano-β-phenyl-cinnamate, glyceryl-2-ethylhexylα-cyano-β-phenylcinnamate, mono-2-ethylhexanoyl-di-p-methoxycinnamate, and ferulic acid and its derivatives; benzophenone-based ultraviolet absorbers, such as 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 Ethyl 2-ethylhexyl-4'-phenyl-benzophenone 2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenon; 3- (4'-methylbenzylidene) -d, 1-camphor; 3-benzylidene-d, 1-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2- (2'-hydroxy-5'-t-octiphenyl) benzotriazole; 2- (2'-hydroxy-5'-methylphenyl) benzotriazole; dibenzalazine; dianisoilmethane; 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one; derivatives of dibenzoylmethane such as 4-t-butylmethoxydibenzoylmethane; octiltriazone; derivatives of urocanic acid, such as urocanic acid and ethyl urocanate; 2- (2'-hydroxy-5'-methylphenyl) benzotriazole; 1- (3,4-dimethoxyphenyl) -4,4-dimethyl-1,3-pentanedione; hydantoin derivatives such as 2-ethylhexyl dimethoxybenzylidene dioxoimidazolidine methyl propionate; sulfonic phenylbenzimidazole; terephthalene-dicanfor dicanforsulfonic sulfonic acid; drometrizole trisiloxane; methyl anthranylate; rutin and its derivatives; and oryzanol and its derivatives.
[00118] Preferred examples of the bleaching agent include: hydroquinone glucoside, such as arbutin and α-arbutin, and their esters; ascorbic acid derivatives such as ascorbic acid, ascorbic acid phosphate ester salts such as sodium ascorbic acid phosphate salt and ascorbic acid phosphate magnesium salt, ascorbic acid fatty acid esters such as ester ascorbic acid tetraisopalmitate, ascorbic acid alkyl ether such as ascorbic acid ethyl ether, ascorbic acid glycoside such as ascorbic acid-2-glucoside and a fatty acid ester, ascorbic acid sulfate ester, and ascorbyl phosphate ester tocopherol; kojic acid; ellagic acid, tranexamic acid and its derivatives; ferulic acid and its derivatives; placenta extract; glutathione; oryzanol; butyl resorcinol; and plant extracts, such as chamomile oil-soluble extract, oil-soluble liquorice extract, Seikariu extract, and Saxifraga herb extract.
[00119] Preferred examples of the vitamin group and its derivatives include: vitamin A, such as retinol group, retinol acetate, and retinol palmitate; vitamin B group, such as thiamine hydrochloride salt, thiamine sulfate salt, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinic acid group as nicotinic acid amide and benzyl nicotinate, and choline; vitamin group C such as ascorbic acid and its salts, such as a sodium salt; D vitamin; vitamin E, such as group Yyα, β, y, δ-tocopherol; other vitamins, such as biotin and pantothenic acid; ascorbic acid derivatives such as ascorbic acid phosphate ester salts such as ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt, ascorbic acid fatty acid esters, such as tetraisopalmitate ascorbic acid ester ascorbyl, stearate, ascorbyl palmitate, and ascorbyl, dipalmitate, alkyl ether-ascorbic acid such as ascorbic acid ethyl ether, ascorbic acid glucoside such as ascorbic acid-2-glucoside and fatty acid from an ester thereof, and tocopherol ascorbyl phosphate; vitamin derivatives, such as tocopherol derivatives, such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulic acid, and tocopherol phosphate; tocotrienol; and various vitamin derivatives.
[00120] Preferred examples of the hair growth agent, blood circulation accelerator, and stimulant include: plant extracts / tinctures such as Swertia japonica extract, capsicum tincture, Zingiber officinale ROSC tincture, Zingiber officinale extract ROSC, and cantharids tincture; capsaicin; vanylylamide nonilic acid; zingerone; Ichthammol; tannic acid; borneol; ciclandelate; cinnarizine; tolazoline; acetylcholine; verapamil; cepharanthine; y-oryzanol; vitamin E and its derivatives, such as tocopherol nicotinate and tocopherol acetate; y-oryzanol; nicotinic acid and its derivatives, such as nicotinic amide, benzyl nicotinate, inositol hexanicotinate, and nicotinic alcohol; allantoin; a photosensitive element 301; a photosensitive element 401; capronium chloride; pentadecanoic acid monoglyceride; flavanonol derivatives; stigmasterol or stigmastanol and glucoside thereof; and minoxidil.
[00121] Preferred examples of hormones include estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, and prednisone. Examples of the anti-wrinkle agent, the anti-aging agent, the tightening agent, the cold detection agent, the hot detection agent, the wound healing promoter, the irritant mitigator, the pain reliever, and the cell activator like other medical agents include : retinols, retinoic acids and tocopheril retinoate; lactic acid, glycolic acid, gluconic acid, fruit acid, salicylic acid, and glucoside and the ester compounds thereof; α- or β-hydroxy acids and their derivatives, such as hydroxycapric acid, long-chain α-hydroxy fatty acids, and long-chain α-hydroxy fatty acid cholesterol esters; Butyric acid Y-amino and Y-amino-e-hydroxy-butyric acid; carnitine; carnosine; creatine; ceramides and sphingosines; caffeine and xanthine, and their derivatives; antioxidants / active agents, such as oxygen scavenging to coenzyme Q10, carotene, lycopene, astaxanthin, lutein, α-lipoic acid, platinum nanocolloid, and fullerenes; catechins; flavones, such as quercetin; isoflavones; and ester of gallic acid saccharides derived therefrom; polyphenols, such as tannin, sesamine, protoanthocyanidin, chlorogenic acid, polyphenols and apple; rutin and its derivatives such as glucoside; hesperidin and its derivatives such as glucoside thereof; lignan glycoside; liquorice extract-related substances, such as glabridin, glabrene, liquiritin, and isoliquiritin; lactoferrin; shogaol and gingerol; perfumery material such as menthol and cedrol, and their derivatives; capsaicin and vanillin, and their derivatives; insect repellents such as diethyltoluamide; complexes of biologically active substances and cyclodextrins.
[00122] Examples of plant / animal / microbe extracts include extracts such as iris extract, Angelica keiskei extract, hiba arborvitae extract, asparagus extract, avocado extract, Hidrangea serrata extract, almond extract, althea extract, extract arnica, aloe extract, apricot extract, apricot seed extract, Gingko biloba extract, Artemisia capillaris flower extract, fruit fennel extract, turmeric root extract, oolong tea extract, leaf extract bearberry extract, pink multiflora extract, Echinacea angustifolia leaf extract, Isodon japonicus extract, Scutellaria baicalensis root extract, phellodendron bark extract, rhizome coptis extract, Hordeum vulgare seed extract, Panax ginseng extract, Hipericum extract , Lamium extract album, Ononis spinosa extract, Nasturtium officinale extract, orange extract, dried seawater, seaweed extract, Japanese persimmon leaf extract, Piracantha fortu neana extract, hydrolyzed elastin, hydrolyzed wheat flour, hydrolyzed silk, pueraria root extract, chamomile extract, oil-soluble chamomile extract, carrot extract, Artemisia capillaris flower extract, wild oat extract, hibiscus extract, licorice extract, oil-soluble liquorice extract, kiwi fruit extract, kyou extract, Auricularia auricula extract, cinchona bark extract, cucumber extract, paulownia leaf extract, guanosine, guava extract, sophora root, Gardenia florida extract, Sasa veitchii extract, Sophora angustifolia extract, walnut extract, Japanese chestnut extract, grapefruit extract, clematis extract, black rice extract, brown sugar extracted substance, black vinegar, chlorella extract, Morus alba root extract, gentiana lutea extract, herb geranium extract, black tea extract, yeast extract, magnolia bark extract, coffee extract, burdock extract, rice extract, fermented rice extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, Vaccinium vitis-idaea extract, Asiasarum root extract, bupleurum root extract, umbilical extract, extract Saffron, Salvia officinalis extract, Saponaria officinalis extract, Sasa bamboo grass extract, Crataegus cuneata fruit extract, Bombix mori excrementum extract, Zanthoxilum piperitum extract, shiitake extract, Rehmannia root extract, Perosithum root, Lithospermum extract frutescens extract, Tilia cordata flower extract, Filipendula multijuga extract, Jatoba extract, Paeonia albiflora extract, Zingiber officinale ROC extract, Acorus calamus extract, Betula alba extract, Tremella fusciformis extract, Equisetum arvense extract, Stevia extract Stevia rebaudiana fermentation product, Seikariu extract, Hedera helix L. extract, Crataegus oxiacantha extract, Sa extract mbucus nigra, Achillea millefolium extract, Mentha piperite leaf extract, sage extract, Malva silvestris extract, Cnidium officinale root extract, Swertia japonica extract, mulberry bark extract, rhuharb extract, soy extract, fruit extract ziziphus, thyme extract, dandelion extract, lichenes extract, tea extract, Eugenia cariophillus flower extract, Imperata cylindrical extract, aurantii nobilis Pericarpium extract, tea tree oil, tencha extract, red pepper extract, extract extract angelica root, Calendula officinalis extract, semen persicae, Citrus aurantium bark extract, Houttuinia cordata extract, tomato extract, natto extract, ginseng extract, garlic extract, Rosa canina fruit extract, hibiscus extract, Ophiopogon tuber extract, Nelumbo nucifera extract, parsley extract, birch extract, honey, hamamelis extract, Parietaria officinalis extract, Isodonis japonicus extract, bis abolol, Chamaeciparis obtusa extract, Lactobacillus bifidus extract, Eriobotria japonica Extract, coltsfoot flower extract, Petasites japonicus extract, Poria coconuts extract, broom butcher extract, grape extract, grape seed extract, propolis extract Luffa cylindrical fruit, saffron flower extract, mint extract, Tilia miqueliana extract, Paeonia suffruticosa root extract, hops extract, Rosa rugosa flower extract, pine cone extract, horse chestnut extract, Japanese skunk cabbage extract , Sapindus mukurossi peel extract, melissa extract, Cladosiphon okamuranus extract, peach extract, Centaurea cyanus flower extract, eucalyptus extract, Saxifraga sariceous extract, Citrus junos extract, lily extract, coix seed extract, princeps Artisia , lavender extract, green tea extract, egg shell membrane extract, apple extract, rooibos tea extract, lychee extract, alf extract ace, lemon extract, Forsithiae fructus extract, Astragalus sinicus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, and Sanguisorba officinalis extract.
Examples of the antipruritic agent include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, and a P-substance inhibitor.
[00124] Examples of the corneum releasing / dissolving agent include salicylic acid, sulfur, resorcin, selenium sulfide, and pyridoxine.
[00125] Examples of the antiperspirant include hydroxy aluminum chlorine, aluminum chloride, zinc oxide, and zinc p-phenolsulfonate.
[00126] Examples of the refrigerant include menthol and methyl salicylate.
[00127] Examples of the astringent agent include citric acid, tartaric acid, lactic acid, aluminum and potassium sulfate, and tannic acid.
[00128] Examples of enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, and protease.
[00129] Preferred examples of nucleic acids include ribonucleic acids and their salts, Deoxyribo nucleic acids and their salts, and adenosine triphosphate disodium.
[00130] Preferred examples of the perfume include synthetic perfumes, natural perfumes, and various compound perfumes, such as cedrene acetyl, amylcinnamaldehide, alliamyl glycolate, β-ionone, Iso E Super, isobutyl quinoline, iris oil, irone, indole, ilang ilang , undecanal, undecenal, y-undecalactone, estragole, eugenol, oak moss, Opopanax resinoid, orange oil, eugenol, aurantiol, Galaxolide, carvacrol, l-carvone, camphor, canon, carrot seed oil, clove oil, geraniol, nitrile geranyl, ethyl isobornyl, geranyl acetate, dimethylbenzylcarbinyl acetate, ethyl stiralyl, ethyl cedril, terpinyl acetate, p-tert-butylcyclohexyl acetate, vetiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santalol, cyclamen aldehyde, cyclopentadecanolide, methyl jasmonate, dihydromyrcenol, Jasmine Absolute, lactone jasmine, cis-jasmine, citral, citronelol, citronellal, oil cinnamon bark, 1,8-cineol, cinnamaldehyde, Stirax resinoid, cedarwood oil, cedrene, cedrol, celery seed oil, thyme oil, damask, damascenone, thymol, absolute tuberose, decanal, decalactone, terpineol , y-terpinene, triple, nerol, nonanal, 2,6-nonadienol, patchouli alcohol, absolute vanilla, vanillin, basil oil, patchouli oil, hydroxycitronellal, α-pinene, piperitone, phenethyl, phenylacetoaldehide, petitgrain oil, hexylcinnamaldehide cis-3-hexenol, peruvian balm, vetiver oil, vetiverol, peppermint oil, pepper oil, heliotropin, bergamot oil, benzyl benzoate, borneol, myrrh resinoid, musk ketone, methilnonilacetoaldehide, y-methilionone , menthol, l-menthol, l-mentone, eucalyptus oil, β-ionone, lemon oil, lavender oil, d-limonene, linalool, lilial lily, oil, lemon, absolute rose, rose oxide, rose oil , rosemary oil, and various refined oils.
[00131] Preferred examples of dye, dye, dye and pigment include legal dyes, such as brown No. 201, No. 401 black, violet No. 201, Violet No. 401, Blue No. 1, Blue Sem. 2, Blue No. 201, Blue No. 202, Blue No. 203, Blue No. 204, Blue No. 205, Blue No. 403, Blue No. 404, Green No. 201, Green 202, Green Without 204., Green No. 205, Green No. 3, No. 401 Green, Green No. 402, Red No. 102, Red No. 104-1, Red No. 105-1, Red No. 106, Red No. 2, Red No. 201, Red 202, Red No. 203, Red No. 204, Red No. 205, Red No. 206, Red No. 207, Red No. 208, Red No. 213, Red No. 214, No. 215 red, Red No. 218, Red N ° 219, Red N ° 220, Red N ° 221, Red N ° 223, Red N ° 225, Red N ° 226, Red N ° 227, Red No. 228, Red No. 230-1, Red No. 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 N ° 503, Red N ° 504, Red N ° 505, Red N ° 506, Orange N ° 201, Orange N ° 203, Orange N ° 204, Orange N ° 205, n ° 206 Orange, Orange No. 207 , Orange No. 401, Orange 402, Orange No. 403, Yellow 201, Yellow 202-1, 202-2 Yellow Yellow o 203 Yellow 204 Yellow 205, Yellow 4, Yellow 401, Yellow 402, 403-1 Yellow Yellow 404 Yellow 405 Yellow 406 Yellow 407, and yellow 5; Acid 14 Red and other acid dyes; basic dyes, such as Arianor Sienna Brown, Arianor Madder Red, Arianor Blue Steel, and Arianor straw yellow; dyes such as nitro HC Iellow 2, HC Iellow 5, HC Red 3, 4-hydroxypropylamino-3-nitrophenol, N, N'-bis (2-hydroxyethyl) -2-nitro-p-phenylenediamine, HC Blue 2 and basic Blue 26; dispersed dyes; white inorganic pigments such as titanium dioxide and zinc oxide; inorganic-based red pigments, such as iron oxide (red iron oxide) and iron titanate; brown inorganic based pigments, such as y- ferric oxide; yellow inorganic based pigments such as yellow and ocher iron oxide; black inorganic based pigments such as black iron oxide and black titanium oxide of lower order; inorganic violet-based pigments, such as mango violet and cobalt violet; inorganic green-based pigments, such as chromium oxide, chromium hydroxide, cobalt and titanate; blue inorganic base pigments such as ultramarine blue and Prussian blue; pigments, such as titanium pearls coated with mica oxide, titanium oxide coated with bismuth oxychloride, titanium talc covered with oxide, mica coated with titanium-oxide, bismuth oxychloride, and guanine fish scale; powdered metal pigments, such as aluminum powder, copper powder, and gold; inorganic and metallic powder pigments with treated surface; Organic pigments such as zirconium, barium, or aluminum lacquer; organic pigments with the treated surface; natural dyes and dyes, such as anthraquinones such as astaxanthin and alizarin, naphthoquinones such as β-carotene, catenal, capsanthin, chalcone, cartamine, quercetin, crocin, chlorophyll, curcumin, cochineal, and shikonin, bixin, flavones, betacianine , hemoglobin, lycopene, riboflavin, and rutin; oxidation dyes and couplers, such as p-phenylenediamine, toluene-2,5-diamine, o-, m- or p-aminophenol, mphenylenediamine, 5-amino-2-methylphenol acid, resorcin, 1-naphthol, and 2,6-diaminopyridine and its salts; naturally oxidized type dyes, such as indoline; and dihydroxyacetone.
[00132] Preferred examples of the antiphlogistic agent and the anti-inflammatory agent include glycyrrhizic acid and its derivatives; glycyrrhetic acid derivatives; derivatives of salicylic acid; hyquititiol; guaiazulene; allantoin; indomethacin; ketoprofen; ibuprofen; diclofenac; loxoprophene; Celecoxib; Infliximab; Etanercept; zinc oxide; hydrocortisone ethyl acetate; prednisone; diphenhydramine hydrochloride; chlorpheniramine maleate; and plant extracts, such as peach leaf extract and Artemisia princeps leaf extract.
[00133] Preferred examples of the antiasthmatic agent, the chronic obstructive anti-pulmonary agent of the disease, the antiallergic agent, and the immunomodulators include aminophylline, theophylline, steroids (fluticasone, beclomethasone, and the like), leukotriene antagonists, thromboxane inhibitors , Intal β -2 stimulants (formoterol, salmeterol, salbutamol, tulobuterol, clenbuterol, epinephrine, and the like), tiotropium, ipratropium, dextromethorphan, dimemorphan, bromhexine, tranilast, ketotiphen, azelastine, cetirizine, tyrrhenine, chlorpheniramine, chlorhenylamine sirolimus, methotrexate, cytokine regulating agents, interferon, omalizmab, and protein / antibody formulations.
[00134] Preferred examples of the disease anti-infective agent and the antifungal agent include oseltamivir and zanamivir, and itraconazole. In the dispersion composition of the present invention, publicly known ingredients for cosmetics, medicines and foods, such as ingredients described in Japanese cosmetic ingredient standards, Japanese cosmetic ingredients Codex, the list can be mixed with other additives. Japan Cosmetic Industry Association of the displayed names of ingredients, the INCI dictionary (the International Cosmetic Dictionary and Handbook ingredient), the Japanese quasi-drug ingredient standards, the Japanese pharmacopeia, the Japanese pharmaceutical excipients, and the Japan specifications and Standards for food additives and ingredients described in the patent Unexamined publications and patents Application Publications (including Japanese or each translation of PCT International publications and PCT Publications International republishments) from Japan and several other countries that are classified by the International Patent Classification in A6 1K7 lessons and A61K8, in a publicly known combination and in a publicly known mix / amount mix ratio. <Method for the formation of hydrogel>
[00135] In the present invention, using the dispersion described above, that is, a dispersion that contains a type of lipid peptide compound, a dissolution accelerator, a polyhydric alcohol, and a polymeric emulsifier, and a dispersion that additionally contains a perfecting agent of heat resistance, a hydrogel can be formed by the following processes. a) process of adding the above dispersing agent to the water and heating the resulting mixture to an ambient temperature or higher and lower than 100 ° C. b) cooling the mixture, with stirring, until the temperature of the mixture becomes lower than the temperature in the heating process.
[00136] The additive described above for cosmetics or additive for quasi-drugs can be added to water, simultaneously with the dispersing agent, in process a).
[00137] In process a), the heating temperature is preferably 50 ° C to 90 ° C and more preferably 60 ° C to 90 ° C, for example 70 ° C or 80 ° C. Preferably, the mixture is stirred while heating the mixture.
[00138] In process a), although the heating and stirring time of the mixture is not particularly limited, for example, the heating time is 6 hours immediately after the addition of the dispersing agent, preferably it can be properly selected at from 30 minutes to 3 hours after adding the dispersing agent.
[00139] Subsequently to process a), a process b) of cooling the mixture, with stirring, until the temperature of the mixture becomes lower than the temperature of process a), is carried out. Here, the temperature at which the mixture is cooled to room temperature is 80 ° C, preferably room temperature up to 40 ° C. <hydrogel>
[00140] The hydrogel formed using the above dispersion and the gel obtained through the above production method are also within the scope of the present invention.
[00141] Hereinafter, the present invention is described in detail with reference to the Examples and Test Examples, which are not to be construed as limiting the present invention.
[00142] [Synthesis Example 1: Synthesis of the lipid peptide (N-palmitoyl-Gly-His)]
[00143] The lipid peptide used as the ice cream, in the present example was synthesized by the method described below.
[00144] In a 500 ml four-necked flask, 14.2 g (91.6 mmol) of histidine, 30.0 g (91.6 mmol) of N-palmitoyl-glymethyl, and 300 g of toluene 35.3 g (183.2 mmol) of a 28% methanol solution with sodium methoxide as base was added to them, followed by heating the resulting reaction mixture in an oil bath at 60 ° C and stirring the reaction mixture for 1 hour. Then, the oil bath was removed and the reaction mixture was allowed to cool to 25 ° C. The reaction mixture was subjected to reprecipitation in 600 g of acetone and the resulting precipitate was filtered. The obtained solid was dissolved in a mixed solution of 600 g of water and 750 g of methanol and to the resulting solution, 30.5 ml (183.2 mmol) of 6N hydrochloric acid was added to neutralize the solution to deposit a solid, followed by filtration The solid. Then, the obtained solid was dissolved in a liquid mixture of 120 g of tetrahydrofuran and 30 g of water at 60 ° C and to the resulting solution, 150 g of ethyl acetate was added, followed by cooling the resulting mixture from 60 ° C to 30 ° C. Then, a deposited solid was filtered. In addition, the obtained solid was dissolved in a solvent of 120 g of tetrahydrofuran and 60 g of acetonitrile and the resulting solution was heated to 60 ° C, followed by stirring the solution for 1 hour. Then, the solution was cooled and the resulting precipitate was filtered. The obtained solid was washed with 120 g of water and the solid was filtered, followed by drying the solid under reduced pressure to obtain 26.9 g (yield: 65%) of a white crystal of one-His N-palmitoyl-Gly. free form (hereinafter also simply called Pal-GH).
[00145] [Example 1 with Example 6, Comparative Example 1: Preparation of dispersions using various accelerators of dissolution and evaluation of dispersibility thereof]
[00146] In a sample tube (No. 7; manufactured by Maruemu Corporation), the Pal-GH obtained by the Synthesis Example above and one of several dissolution accelerators shown in Table 1 were weighed and loaded so that the composition The mixture became the composition (mass: g) shown in Table 1, and the resulting mixture was heated and stirred in a water bath set at about 80 ° C to obtain a Pal-GH dispersion.
[00147] Then, the dispersibility of Pal-GH after heating and stirring the mixture at 80 ° C was visually evaluated according to a criterion such that a dispersion in which the Pal-GH powder was homogeneously dispersed (a clear solution was obtained) was evaluated as O and a dispersion in which the Pal-GH powder was not homogeneously dispersed (for example, a whitish dispersion, including a lump of the Pal-GH powder) was evaluated as X. The results obtained are also shown in Table 1. [Table 1]
Chemicals Co., Ltd. AMPHITOL 86B: stearyl betaine manufactured by Kao Corporation AMPHITOL 20AB: lauramidopropyl betaine manufactured by Kao Corporation AMPHITOL 20HD: lauryl sulfobetai6 ^ a hydroxy manufactured by Kao Corporation AMPHITOL 20BS: lauryl betaine manufactured by Kao Corporation LPC-1: gem of lysolecithin egg manufactured by the Kewpie Corporation
[00148] [Example 7 to Example 10: Preparation of dispersion using polyhydric alcohol and heat resistance enhancer and dispersibility assessment thereof]
[00149] In a sample tube (No. 7; manufactured by Maruemu Corporation), the Pal-GH obtained by the above synthesis Example and a dissolution accelerator, a polyhydric alcohol, and an enhancer heat resistance shown in Table 2 were weighed and loaded so that the composition of the mixture became the composition (in mass: g) shown in Table 2, and the resulting mixture was heated and stirred in a water bath set at 80 ° C to obtain a Pal-GH dispersion.
[00150] Then, the dispersibility of Pal-GH after heating and stirring the mixture at 80 ° C was visually evaluated according to a criterion such that a dispersion in which the Pal-GH powder was homogeneously dispersed (a clear solution was obtained) was evaluated as O and a dispersion in which the Pal-GH powder was not homogeneously dispersed (for example, a whitish dispersion, including a lump of the Pal-GH powder) was evaluated as X.
[00151] The results obtained are also shown in Table 2. [Table 2]
* AMPHITOL 20HD: lauryl hydroxysulfobetaine manufactured by Kao Corporation 1,3-BG: 1,3-butylene glycol manufactured by Ito Inc. Lauryl alcohol: manufactured by Kao Corporation Nikoi, MGS-AV: glyceryl monostearate manufactured by Nikko Chemicals Co., Ltd. NIKKOL MGS-F75: glyceryl monostearate containing 75% monoglyceride manufactured by Nikko Chemicals Co., Ltd.
[00152] [Example 11 and Example 12: gelation test, using Pal-GH dispersion and propylene glycol alginate in combination]
[00153] In a 300 ml tall glass, as shown in Table 3, the pure water and propylene glycol alginate (PG also called alginate) were loaded and the resulting mixture was heated and stirred at 70 ° C. Stirring was carried out using a high LABORATORY mixer manufactured by as a corporation at 200 rpm.
[00154] Then, 1.00 g of the Pal-GH dispersion of Example 1 or Example 4, which was heated to 70 ° C was added thereto and the resulting mixture was further heated and stirred for 5 minutes.
[00155] After the heating stopped, the mixture was stirred and cooled until the temperature of the mixture reached about 40 ° C and it was confirmed that a gel was formed. The confirmation of gel formation was carried out by the test tube inversion method and a state in which the fluidity of the dispersion was lost and when the height cup was inverted, the dispersion did not flow downwards was assessed as "gelled (□)" . On the contrary, a state in which no gel formation was observed was assessed as "□". The final composition after the gelation test and the test results obtained are shown in Table 3. [Table 3]

[00156] [Example 13 to Example 16: Confirmation of the heat resistance enhancing effect]
[00157] In a high cup of 300 ml, as shown in Table 4, water and pure alginate propylene glycol were loaded and the resulting mixture was heated and stirred at 70 ° C. Stirring was carried out using a high Ixer laboratory manufactured by as a corporation at 200 rpm.
[00158] Next, each of the Pal-GH dispersions of Examples 7 to 10 that were heated to 70 ° C was added in the amount indicated in Table 4 and the resulting mixtures were each further heated and stirred for 5 minutes.
[00159] After the heating stopped, the mixture was stirred and cooled until the temperature of the mixture reached about 40 ° C and it was confirmed that a gel was formed. The confirmation of gel formation was carried out by the test tube inversion method and a state in which the fluidity of the dispersion was lost and when the height cup was inverted, the dispersion did not flow downwards was assessed as "gelled (O)" . On the contrary, a state in which no gel formation was observed was rated "x". The final composition after the gelation test and the test results obtained are shown in Table 4.
[00160] After a portion of the resulting gel was placed in a No. 7 sample tube (Maruemu Corporation) and stored at 40 ° C overnight, if insoluble materials were present in the gel it was evaluated visually according to such a criterion that a dispersion that does not contain insoluble matters was rated as "thermally stable at 40 ° C (O)" and a dispersion that contains insoluble matter was rated as "not thermally stable at 40 ° C (x". The results also obtained are shown in Table 4. [Table 4]

权利要求:
Claims (14)
[0001]
1 .- "DISPERSION", comprising a peptide-type compound in which a part of the peptide formed by the repetition of at least two or more identical amino acids is linked to a lipid part including an aliphatic group C10-24, a dissolution accelerator having, in molecules thereof, a hydrophilic part and a hydrophobic part, the hydrophilic part having a betaine and water structure, characterized in that the peptide-type compound contains at least one of the compounds of Formula (1) to Formula (3) and pharmaceutically usable salts of compounds:
[0002]
2 .- "DISPERSION", according to claim 1, characterized in that it comprises a polyhydric alcohol.
[0003]
3 .- "DISPERSION", according to any of the preceding claims, characterized in that the dissolution accelerator is at least one selected from betaine aminoacetic acid, betaine lauryl dimethyl amino acetic acid, stearyl betaine, and lysophosphatylcholine.
[0004]
4.- "DISPERSION" according to claim 3, characterized in that it contains a type of lipid peptide composed as a gelling agent and also contains a polymeric emulsifier.
[0005]
5 .- "DISPERSION" according to any one of the preceding claims, characterized in that the dispersion is a pre-mixture for the preparation of a cosmetic or a pseudo-medicine.
[0006]
6 .- "DISPERSION" according to claim 4, characterized in that the dispersion is used as a thickener for an antifreeze fluid.
[0007]
7. "DISPERSION" according to claim 5, characterized in that the polymer emulsifier is a polymer compound selected from the group consisting of a graft polymer compound in which a hydrophobic fraction is grafted onto a hydrophilic skeleton and a block polymer compound containing a hydrophobic structural unit and a hydrophilic structural unit.
[0008]
8 .- "DISPERSION", according to claim 6 or 7, characterized by improving heat resistance.
[0009]
9. - "DISPERSION" according to claim 8, characterized in that the heat resistance enhancer is at least a higher alcohol in the group consisting of higher saturated and unsaturated alcohols C10-20 or at least one fatty acid ester highest selected from the group consisting of higher saturated and unsaturated fatty acid esters C10-20.
[0010]
10 .- "DISPERSION", according to claim 9, characterized in that the heat resistance enhancer is kethanol, myristyl alcohol or glyceryl monostearate.
[0011]
11. - "DISPERSION" according to either of claims 6 or 7, characterized in that the polymer compound is selected from the group consisting of a carboxymethyl cellulose and alginic acid ester.
[0012]
12. - "DISPERSION" according to claim 11, characterized in that the polymer compound is propylene glycol alginate.
[0013]
13 .- "METHOD FOR THE PRODUCTION OF A HYDROGEL", according to any one of claims 3, 5, 6 to 12, characterized by comprising the addition of the dispersion to the water and heating the resulting mixture at a temperature below 100 ° C or at room temperature or higher than 100oC, and cool the mixture with stirring until the temperature of the mixture reaches a temperature lower than the temperature on heating to form a gel.
[0014]
14 .- "HYDROGEL", characterized in that it contains the dispersion described in any one of claims 4, 5 and 7 to 13.

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法律状态:
2018-01-23| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|

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2018-05-15| B07B| Technical examination (opinion): publication cancelled [chapter 7.2 patent gazette]|

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2019-07-30| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-04-28| B07A| Technical examination (opinion): publication of technical examination (opinion) [chapter 7.1 patent gazette]|

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2020-08-11| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|

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2020-10-27| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-01-05| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 03/07/2014, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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JP2013143791|2013-07-09|

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JP2013-143791|2013-07-09|

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PCT/JP2014/067802|WO2015005219A1|2013-07-09|2014-07-03|Dispersion liquid and method for forming hydrogel|

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