WO2015099074A1 - 脂質ペプチド型化合物を含有するスティック状基材 - Google Patents
脂質ペプチド型化合物を含有するスティック状基材 Download PDFInfo
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- WO2015099074A1 WO2015099074A1 PCT/JP2014/084384 JP2014084384W WO2015099074A1 WO 2015099074 A1 WO2015099074 A1 WO 2015099074A1 JP 2014084384 W JP2014084384 W JP 2014084384W WO 2015099074 A1 WO2015099074 A1 WO 2015099074A1
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- ZFNVDHOSLNRHNN-UHFFFAOYSA-N xi-3-(4-Isopropylphenyl)-2-methylpropanal Chemical compound O=CC(C)CC1=CC=C(C(C)C)C=C1 ZFNVDHOSLNRHNN-UHFFFAOYSA-N 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 1
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- 229940105125 zinc myristate Drugs 0.000 description 1
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- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- PICXIOQBANWBIZ-UHFFFAOYSA-N zinc;1-oxidopyridine-2-thione Chemical compound [Zn+2].[O-]N1C=CC=CC1=S.[O-]N1C=CC=CC1=S PICXIOQBANWBIZ-UHFFFAOYSA-N 0.000 description 1
- ZNVKGUVDRSSWHV-UHFFFAOYSA-L zinc;4-hydroxybenzenesulfonate Chemical compound [Zn+2].OC1=CC=C(S([O-])(=O)=O)C=C1.OC1=CC=C(S([O-])(=O)=O)C=C1 ZNVKGUVDRSSWHV-UHFFFAOYSA-L 0.000 description 1
- GBFLQPIIIRJQLU-UHFFFAOYSA-L zinc;tetradecanoate Chemical compound [Zn+2].CCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCC([O-])=O GBFLQPIIIRJQLU-UHFFFAOYSA-L 0.000 description 1
- 239000001243 zingiber officinale rosc. root absolute Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
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Classifications
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
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- A61K8/67—Vitamins
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- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/87—Application Devices; Containers; Packaging
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
Definitions
- the present invention relates to a solid base for external use containing a lipid peptide type compound, preferably a stick type base, and an aqueous composition containing a lipid peptide type compound useful as a premix raw material for the solid base for external use.
- the aqueous solid composition provides a high refreshing feeling when applied to the skin, etc., and has no stickiness after use as compared to the oily solid composition, so that it has a smooth use feeling.
- a variety of products are marketed and proposed.
- As an aqueous solid composition conventionally, a solid oil-in-water makeup cosmetic (Patent Document 1) containing water, fatty acid soap, oil and powder, an alkyl and / or alkenyl oligoglycoside, an oily substance, and a nonionic emulsifier
- Patent Document 2 A stick-like water-based cosmetic
- an aqueous gel composition is mentioned as a kind of aqueous solid composition.
- various compounds such as a polymer gelling agent and a low molecular gelling agent have been proposed.
- lipid peptide type low molecular gelling agents that have high biological safety and are expected to be developed into medical materials have been proposed.
- the aqueous gel obtained using the above-mentioned lipid peptide type low molecular gelling agent has a relatively low breaking strength, and it is difficult to develop the product on applications requiring a certain level of strength, such as a stick-like solid base material for external skin.
- Met. This invention is made
- the present inventors form a hydrogel from a lipid peptide type compound (gelator) comprising a low molecular lipid peptide or a pharmaceutically usable salt thereof and water.
- a lipid peptide type compound gelator
- 1,2-alkanediol or glycerin as a solubilizing agent for the lipid peptide type compound and a surfactant
- a gel having remarkably higher breaking strength than before can be obtained.
- the present invention has been completed by finding that it can be suitably used as a material, particularly as a stick-like substrate.
- the present invention provides, as a first aspect, a lipid peptide comprising a surfactant and water, and at least one of a compound represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof:
- the present invention relates to a solid base material for external use containing a type compound.
- R 1 represents an aliphatic group having 9 to 23 carbon atoms
- R 2 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms
- R 3 represents a — (CH 2 ) n —X group, n represents a number of 1 to 4, and X has an amino group, a guanidino group, a —CONH 2 group, or 1 to 3 nitrogen atoms.
- R 4 represents an aliphatic group having 9 to 23 carbon atoms
- R 5 to R 7 each independently represents a hydrogen atom, or a carbon atom number that can have a branched chain having 1 or 2 carbon atoms.
- R 8 represents an aliphatic group having 9 to 23 carbon atoms
- R 9 to R 12 each independently represents a hydrogen atom, or the number of carbon atoms that may have a branched chain having 1 or 2 carbon atoms.
- the present invention relates to the solid base material for external use according to the first aspect, further comprising 1,2-alkanediol or glycerin.
- a 3rd viewpoint it is related with the solid base material for skin external appearance as described in a 1st viewpoint or a 2nd viewpoint which further contains at least 1 type of fatty acid.
- a 4th viewpoint it is related with the solid base material for external skin as described in any one of the 1st viewpoint thru
- a 5th viewpoint it is related with the solid base material for external skin as described in any one of the 1st viewpoint thru
- the surfactant is one or more compounds selected from the group consisting of ethylene glycol alkyl ethers, phospholipids, polyglycerin fatty acid esters, and polyoxyethylene polyoxypropylene alkyl ethers.
- or 5th viewpoint It is related with the solid base material for external use of a skin as described in any one.
- the present invention relates to the solid base for external use as described in any one of the third aspect to the sixth aspect, in which the fatty acid is stearic acid.
- the present invention relates to the solid base material for external use according to any one of the fifth aspect to the seventh aspect, wherein the organic acid is ascorbic acid.
- the present invention relates to the external base material for skin according to any one of the first aspect to the ninth aspect, which is for cosmetics or medicine.
- the solid base material for external skin as described in any one of the 1st viewpoint thru
- a twelfth aspect includes a surfactant and water, and a lipid peptide-type compound comprising at least one of the compounds represented by the formulas (1) to (3) or a pharmaceutically usable salt thereof. Relates to an aqueous composition.
- the aqueous composition according to the twelfth aspect further comprising 1,2-alkanediol or glycerin.
- the aqueous composition of the 12th viewpoint or the 13th viewpoint which further contains at least 1 type of fatty acid.
- the surfactant is one or more compounds selected from the group consisting of ethylene glycol alkyl ethers, phospholipids, polyglycerin fatty acid esters, and polyoxyethylene polyoxypropylene alkyl ethers. It is related with the aqueous composition as described in any one of thru
- the present invention relates to the aqueous composition according to any one of the twelfth aspect to the fifteenth aspect, which is a premix for the preparation of a solid base for external use on the skin.
- a step of heating the aqueous composition according to any one of the twelfth aspect to the sixteenth aspect at a temperature of room temperature to less than 100 ° C. A step of adding and mixing the heated aqueous composition to an aqueous phase heated at a temperature of room temperature to less than 100 ° C., and a step of cooling the resulting mixture to form a gel;
- the manufacturing method of the skin external solid base material as described in a 1st viewpoint containing this.
- the present invention relates to the production method according to the seventeenth aspect, wherein the aqueous phase contains at least one oily base material.
- the present invention relates to the manufacturing method according to the seventeenth aspect, wherein the aqueous phase contains polyethylene glycol.
- the manufacturing method of the external base material for skin as described in a 5th viewpoint containing this.
- the present invention relates to the manufacturing method according to the twentieth aspect, in which the aqueous phase contains at least one oily base material.
- the present invention can provide a weakly acidic solid base material for external skin having a strength higher than that of a conventional aqueous gel-like base material and having a pH of about 5.
- the present invention can provide a solid base material for external application to the skin which is a gel-like base material capable of achieving a water content as high as about 90% by mass, and which can also contain an oil component.
- the lipid peptide compound contained in the solid base material for external use of the present invention is a very safe artificial low molecular weight compound composed only of a lipid and a peptide.
- the compound can form an aqueous gel without using a cross-linking agent or the like required for forming a synthetic polymer gel that has been conventionally proposed, the compound is not yet used in the obtained solid base for external use on the skin. The problem of remaining unreacted substances such as a crosslinking agent in the reaction does not occur.
- each main component contained as an additive in the solid base for external use of the present invention is a general-purpose additive as an additive for foods, cosmetics and pharmaceuticals.
- the solid external base material for skin according to the present invention has high biological safety, and is extremely useful in the above applications from the viewpoint of high safety required especially for medical materials or cosmetic materials.
- the solid external base material for skin according to the present invention has a refreshing feeling when applied to human skin and the like, and is expected to be a base material that does not break or deform and has good elongation. It is very useful as a base material for medical use and a pharmaceutical base material, particularly as a stick-shaped base material.
- this invention can provide the aqueous composition suitable as a premix raw material for the said solid base materials for external use of the skin. And this invention uses the said aqueous composition, The gel-form solid base material for skin external appearance which has the intensity
- the present invention includes a surfactant and water, and a lipid peptide type compound comprising at least one of the compounds represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof,
- the present invention relates to a solid base material for external application of skin containing 1,2-alkanediol or glycerin, fatty acid, oily base material, organic acid, polyethylene glycol, and other additives as desired.
- the present invention also includes the surfactant, water, and the lipid peptide type compound, and optionally includes 1,2-alkanediol or glycerin and a fatty acid, and further includes an oily base material, organic acid, polyethylene glycol, and other additives.
- the solid external base material for skin according to the present invention is suitable for cosmetics or pharmaceuticals, and can be applied particularly as a stick-shaped base material.
- the stick-shaped substrate refers to a rod-shaped substrate having a strength that can be applied to the skin and the like while maintaining the rod-shaped shape.
- the strength required for the stick substrate is, for example, breaking strength: 0.4 ⁇ 10 5 Pa to 8.0 ⁇ 10 5 Pa, preferably 1.0 ⁇ 10 5 Pa to 7.0 ⁇ 10 5 Pa. More preferably, it is 1.0 ⁇ 10 5 Pa to 6.0 ⁇ 10 5 Pa.
- the lipid peptide type compound used in the solid external base for skin or aqueous composition of the present invention includes a compound (lipid peptide) represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof (A low molecular weight compound having a lipid part which is a hydrophobic part and a peptide part which is a hydrophilic part) can be used.
- R 1 represents an aliphatic group having 9 to 23 carbon atoms, and preferably R 1 is a straight chain having 11 to 23 carbon atoms which may have 0 to 2 unsaturated bonds.
- An aliphatic group is desirable.
- Specific examples of the lipid moiety (acyl group) composed of R 1 and an adjacent carbonyl group include lauroyl group, dodecylcarbonyl group, myristoyl group, tetradecylcarbonyl group, palmitoyl group, margaroyl group, oleoyl group, and eridoyl.
- R 2 contained in the peptide part represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms.
- the alkyl group having 1 to 4 carbon atoms that may have a branched chain having 1 or 2 carbon atoms is a branched chain having 1 to 4 carbon atoms in the main chain and 1 or 2 carbon atoms.
- Means an alkyl group which may have, and specific examples thereof include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group or tert-butyl group Etc.
- R 2 is preferably a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may have a branched chain having 1 carbon atom, and more preferably a hydrogen atom.
- the alkyl group having 1 to 3 carbon atoms which can have a branched chain having 1 carbon atom is an alkyl group having 1 to 3 carbon atoms in the main chain and having a branched chain having 1 carbon atom.
- a methyl group an ethyl group, an n-propyl group, an i-propyl group, an i-butyl group, or a sec-butyl group, preferably a methyl group, an i-propyl group, An i-butyl group or a sec-butyl group.
- R 3 represents a — (CH 2 ) n—X group.
- n represents a number of 1 to 4
- X is an amino group, a guanidino group, a —CONH 2 group, or a 5-membered cyclic group having 1 to 3 nitrogen atoms.
- X is preferably an amino group, guanidino group, carbamoyl group (—CONH 2 group), pyrrole group, imidazole group, pyrazole group or indole group, and more Preferably it is an imidazole group.
- n is preferably 1 or 2, and more preferably 1.
- the — (CH 2 ) n- group is preferably an aminomethyl group, 2-aminoethyl group, 3-aminopropyl group, 4-aminobutyl group, carbamoylmethyl group, 2-carbamoylethyl group, 3-carbamoyl group.
- a lipid peptide particularly suitable as a lipid peptide type compound is a compound formed from the following lipid part and peptide part (amino acid assembly part).
- amino acids alanine (Ala), asparagine (Asn), glutamine (Gln), glycine (Gly), histidine (His), isorosine (Ile), leucine (Leu), lysine (Lys), tryptophan (Trp) ), Valine (Val).
- Lauroyl-Gly-His Lauroyl-Gly-Gln, Lauroyl-Gly-Asn, Lauroyl-Gly-Trp, Lauroyl-Gly-Lys, Lauroyl-Ala-His, Lauroyl-Ala-Gln, Lauroyl-Ala-Asn, Lauroyl -Ala-Trp, Lauroyl-Ala-Lys; Myristoyl-Gly-His, Myristoyl-Gly-Gln, Myristoyl-Gly-Asn, Myristoyl-Gly-Trp, Myristoyl-Gly-Lys, Myristoyl-Ala-His, Myristoyl-Ala -Gln, Myristoyl-Ala-Asn, Myristoyl-Ala-Trp, Myristoyl-Ala-Lys; Palmitoyl-Gly-His, Palmitoyl-Gly-Gln, Palmi
- lauroyl-Gly-His lauroyl-Ala-His-myristoyl-Gly-His, myristoyl-Ala-His; palmitoyl-Gly-His, palmitoyl-Ala-His; stearoyl-Gly-His, stearoyl-Ala -His.
- R 4 represents an aliphatic group having 9 to 23 carbon atoms, and preferred specific examples include the same groups as defined for R 1 above.
- R 5 to R 7 each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms, or — ( CH 2 ) nX group, and at least one of R 5 to R 7 represents a — (CH 2 ) nX group.
- n a number of 1 to 4
- X represents an amino group, a guanidino group, a —CONH 2 group, or a 5-membered cyclic group or a 6-membered cyclic group which may have 1 to 3 nitrogen atoms, or a 5-membered ring And a condensed heterocyclic group composed of a 6-membered ring.
- R 5 to R 7 include the same groups as defined for R 2 and R 3 above.
- a preferable lipid peptide is a compound formed from the following lipid part and peptide part (amino acid assembly part).
- Myristoyl-Gly-Gly-His Myristoyl-Gly-Gly-Gln, Myristoyl-Gly-Gly-Asn, Myristoyl-Gly-Gly-Trp, Myristoyl-Gly-Gly-Lys, Myristoyl-Gly-Ala-His, Myristoyl- Gly-Ala-Gln, Myristoyl-Gly-Ala-Asn, Myristoyl-Gly-Ala-Trp, Myristoyl-Gly-Ala-Lys, Myristoyl-Ala-Gly-His, Myristoyl-Ala-Gly-Gln, Myristoyl-Ala- Gly-Asn, Myristoyl-Ala-Gly-Trp, Myristoyl-Ala-Gly-His
- lauroyl-Gly-Gly-His myristoyl-Gly-Gly-His, palmitoyl-Gly-Gly-His, palmitoyl-Gly-His-Gly, palmitoyl-His-Gly-Gly, stearoyl -Gly-Gly-His.
- R 8 represents an aliphatic group having 9 to 23 carbon atoms, and preferred specific examples include the same groups as defined for R 1 above.
- R 9 to R 12 are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms which may have a branched chain having 1 or 2 carbon atoms, or — ( CH 2 ) nX group, and at least one of R 9 to R 12 represents a — (CH 2 ) nX group.
- n a number of 1 to 4
- X represents an amino group, a guanidino group, a —CONH 2 group, or a 5-membered cyclic group or a 6-membered cyclic group which may have 1 to 3 nitrogen atoms, or a 5-membered ring And a condensed heterocyclic group composed of a 6-membered ring.
- R 9 to R 12 include the same groups as defined for R 2 and R 3 above.
- particularly preferred lipid peptides include lauroyl-Gly-Gly-Gly-His, myristoyl-Gly-Gly-Gly-His, palmitoyl. -Gly-Gly-Gly-His, Palmitoyl-Gly-Gly-His-Gly, Palmitoyl-Gly-His-Gly-Gly, Palmitoyl-His-Gly-Gly-Gly, Stearoyl-Gly-Gly-Gly-His, etc. Can be mentioned.
- the amount of the lipid peptide type compound is, for example, 1 to 20% by mass, preferably 1 to 10% by mass, more preferably 4 to 5% by mass, based on the total mass of the obtained external base material for skin. %.
- the compounding amount of the lipid peptide type compound is, for example, 5 to 20% by mass, preferably 10 to 20% by mass, with respect to the total mass of the obtained aqueous composition.
- the lipid peptide type compound used in the present invention comprises at least one of the compounds represented by the above formulas (1) to (3) (lipid peptide) or a pharmaceutically usable salt thereof, and is hydrogelated. These compounds can be used alone or in combination of two or more as an agent.
- a surfactant used in the solid base for external use of skin or the aqueous composition of the present invention a compound having a hydrophilic part and a hydrophobic part in the molecule, and the hydrophilic part having a betaine structure (hereinafter also referred to as a betaine compound) ), Ethylene glycol alkyl ether, polyglycerin fatty acid ester, or polyoxyethylene polyoxypropylene alkyl ether can be suitably used.
- betaine compounds as described above include N-alkyl-N, N-dimethylamino acid betaines such as lauryldimethylaminoacetic acid betaine (lauryl betaine); fatty acid amide alkyl-N such as cocamidopropyl betaine and lauramidopropyl betaine.
- N-dimethylamino acid betaine N-dimethylamino acid betaine; imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkylsulfobetaines such as laurylhydroxysulfobetaine and alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; alkyldimethylaminoethanol Known betaine compounds such as phosphate-type betaines such as phosphate esters can be used as amphoteric surfactants.
- betaine compounds include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), phosphatidic acid and other glycerophospholipids; lysophosphatidylcholine (lysolecithin), lysophosphatidylethanolamine, Examples thereof include lysoglycerophospholipids such as serine, lysophosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidic acid; sphingophospholipids such as sphingomyelin; and hydrogenated products thereof.
- phospholipids may be derived from animals and plants such as soybeans and egg yolks, or may be synthesized by a chemical or enzymatic method.
- betaine compounds preferably lauryldimethylaminoacetic acid betaine, lauric acid amidopropyl betaine, lauryl hydroxysulfobetaine, stearyl betaine, lysophosphatidylcholine (lysolecithin), lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol, lyso Examples thereof include phosphatidylglycerol and lysophosphatidic acid, and more preferably lysophosphatidylcholine (lysolecithin).
- ethylene glycol alkyl ether examples include polyoxyethylene alkyl ether, polyoxyethylene lauryl ether, polyoxyethylene palmitoyl ether, polyoxyethylene stearyl ether and the like. Also, commercially available ethylene glycol alkyl ethers can be used. Examples of such products include Emulgen 102KG, Emargen 103, and Emulgen 104P in Kao's Emulgen (registered trademark) series and Emanon (registered trademark) series.
- Emulgen 103 More preferably, Kao's Emulgen 103, Emulgen 104P, Emulgen 105, Emulgen 106, Emulgen 108, Emulgen 109P, Emulgen 210P, Emulgen 306P, Emulgen 320P, Emulgen 404, Emulgen 408, Emulgen 409PV, Emulgen 420, Emulgen 705 , Emulgen 707, Emulgen 709, Emulgen 1108, Emulgen 2020G-HA, Emanon 1112, Emanon 4110.
- Emulgen 104P More preferably, Kao's Emulgen 104P, Emulgen 105, Emulgen 106, Emulgen 108, Emulgen 210P, Emulgen 306P, Emulgen 408, Emulgen 409PV, Emulgen 705, Emulgen 707, Emulgen 709, Emulgen 1108, Emulgen 2020G-HA, Emanon 1112, Emanon 4110.
- NIKKOL registered trademark
- examples include NIKKOL BT-5, NIKKOL BT-7, NIKKOL BT-9, and NIKKOL BT-12.
- polyglycerin fatty acid ester examples include glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, glyceryl oleate, glyceryl coconut oil fatty acid, mono-cotton oil fatty acid glycerin, glyceryl monosulcate, glyceryl sesquioleate, ⁇ , ⁇ '-Glycerin fatty acid partial esters such as glyceryl oleate, glyceryl monostearate, and malic monostearate; polyglyceryl stearate-2, 3, 4, 5, 6, 6, 8, 10 polyglyceryl distearate 6, same 10, polyglyceryl tristearate-2, polyglyceryl 10 decastearate, polyglyceryl-2 isostearate 3, 3, 4, 5, 6, 8, 8, 10 Liglyceryl-2 (diglyceryl diisostearate), 3, 10, polyglyceryl triisostearate,
- Polyoxyethylene polyoxypropylene alkyl ethers include Kao's Emulgen (registered trademark) LS-106, Emulgen LS-110, Emulgen LS-114, Emulgen MS-110, and Nikko Chemicals' NIKKOL (registered) Trademarks) PBC-31, NIKKOL PBC-33, NIKKOL PBC-34, NIKKOL PBC-41, NIKKOL PBC-44, NIKKOL PBN-4612, NIKKOL PBN-4620, NIKKOL PBN-4630. More preferred are Emulgen LS-106, Emulgen LS-110, Emulgen LS-114, and Emulgen MS-110. More preferred are Emulgen LS-106, Emulgen LS-110, and Emulgen MS-110.
- surfactant used in the present invention those having an HLB (Hydrophile-Lipophile Balance) value of 8 to 20 can be preferably used. More preferably, the HLB value is 8 to 14.
- HLB Hydrophile Balance
- surfactants include sorbitan isostearate, steareth-8, behenez-10, laureth-5, ceteth-7, oleth-8, PEG-8 glyceryl isostearate, choles-10, and PEG-10BG isostearate.
- the compounding amount of the surfactant is, for example, 1 to 20% by mass, preferably 1 to 10% by mass, more preferably 1 to 5% by mass, based on the total mass of the obtained external base material for skin. It is. In this invention, the compounding quantity of surfactant is 1-20 mass% with respect to the total mass of the aqueous composition obtained, Preferably it is 2-10 mass%.
- the surfactant used in the present invention is at least one of the above-mentioned surfactant group, and these surfactants can be used alone or in combination of two or more.
- the solid external base for skin or the aqueous composition of the present invention may contain 1,2-alkanediol.
- 1,2-alkanediol has a function of promoting the solubility of the lipid peptide type compound.
- Specific examples of the 1,2-alkanediol include 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, and the like. Preferred are 1,2-pentanediol, 1,2-hexanediol, and 1,2-octanediol.
- 1,2-pentanediol or 1,2-hexanediol More preferred is 1,2-pentanediol or 1,2-hexanediol.
- the 1,2-alkanediol used in the present invention is at least one of the aforementioned 1,2-alkanediol group, and these 1,2-alkanediols can be used alone or in combination of two or more.
- glycerin in addition to the 1,2-alkanediol, can also be suitably used as having a function of promoting the solubility of the lipid peptide type compound. .
- the above-mentioned surfactants include products that contain glycerin as a solvent in commercially available products, and when this commercially available product is used, glycerin contained as a component also acts to promote the solubility of lipid peptide type compounds.
- the amount of 1,2-alkanediol or glycerin is, for example, 1 to 20% by mass, preferably 1 to 10% by mass, more preferably, based on the total mass of the obtained external base material for skin. 1 to 5% by mass.
- the blending amount of 1,2-alkanediol or glycerin is, for example, 2 to 20% by mass, preferably 2 to 10% by mass with respect to the total mass of the resulting aqueous composition.
- the solid base for skin or the aqueous composition of the present invention may further contain a fatty acid.
- the fatty acid used in the present invention is preferably at least one selected from the group consisting of saturated and unsaturated fatty acids having 10 to 20 carbon atoms and salts of these fatty acids.
- Examples of fatty acids include capric acid and undecane. Examples include acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, and stearic acid. More preferably, capric acid, lauric acid, myristic acid, palmitic acid, and stearic acid are mentioned, and stearic acid is particularly preferable.
- the amount of fatty acid used is, for example, 0.1 to 2.0 mass%, preferably 0.2 to 1.0 mass%, based on the total mass of the obtained external base material for skin. is there.
- the compounding quantity of a fatty acid is 0.5 to 5 mass% with respect to the total mass of the aqueous composition obtained, Preferably it is 0.5 to 3 mass%.
- the fatty acid used in this invention is at least 1 sort (s) selected from the said fatty acid group, These fatty acids can be used individually or in combination of 2 or more types.
- the solid base material for external use of the present invention may further contain an oily base material.
- the aqueous composition of the present invention may also contain an oily substrate.
- the oily base used in the present invention include cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, stearyl alcohol, aralkyl alcohol, behenyl alcohol, jojoba alcohol, chimyl alcohol, seraalkyl alcohol, batyl alcohol, Higher (polyhydric) alcohols such as hexyldecanol, isostearyl alcohol, 2-octyldodecanol, dimer diol; aralkyl alcohols such as benzyl alcohol and derivatives thereof; isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmi Tooleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, do
- the blending amount of the oily base material is, for example, 1 to 50% by mass, preferably 5 to 50% by mass, more preferably 10 to 50% by mass, with respect to the total mass of the obtained external base material for skin. It is.
- the compounding quantity is 50-1 mass% with respect to the total mass of an aqueous composition, for example, Preferably, it is 30-1 mass%.
- the said oily base used in this invention is at least 1 type of the above-mentioned oily base group, These oily bases can be used individually or in combination of 2 or more types.
- the solid base material for external use of the present invention may further contain an organic acid.
- the aqueous composition of the present invention may also contain an organic acid.
- the organic acid include ascorbic acid, citric acid, lactic acid, glycolic acid, succinic acid, acetic acid, malic acid, tartaric acid, and fumaric acid. Among them, ascorbic acid, citric acid, and lactic acid are preferable, and ascorbic acid and citric acid are particularly preferable.
- the compounding quantity of an organic acid is 1 to 20 mass% with respect to the total mass of the solid base material for external use obtained, Preferably it is 1 to 10 mass%.
- the compounding quantity is 1 to 20 mass% with respect to the total mass of an aqueous composition, for example, Preferably, it is 1 to 10 mass%.
- the solid base for external use of the present invention may further contain polyethylene glycol.
- the aqueous composition of the present invention may also contain polyethylene glycol.
- polyethylene glycol By including polyethylene glycol, the temporal stability of the solid base material for external use on the skin can be improved.
- the polyethylene glycol for example, those having an average molecular weight of 1,000 to 4,000 can be suitably used.
- the blending amount of polyethylene glycol is, for example, 1 to 20% by mass, preferably 1 to 10% by mass, based on the total mass of the obtained external base material for skin.
- the compounding quantity is 1 to 20 mass% with respect to the total mass of an aqueous composition, for example, Preferably, it is 1 to 10 mass%.
- Additives that can be generally used as cosmetic additives and quasi-drug additives can be blended with the solid base for external use or the aqueous composition of the present invention as needed.
- humectants and feel improvers examples include glycerin, 1,3-butylene glycol (1,3-butanediol), propylene glycol, 3-methyl-1,3-butanediol, 1,3-propanediol, and 2-methyl.
- Polyols such as -1,3-propanediol, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, ethylene glycol / propylene glycol copolymer, and the like Its polymers: diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol dibutyl ether Glycol alkyl ethers such as water-soluble esters such as (eicosandioic acid / tetradecandioic acid) polyglyceryl-10 and tetradecandioic acid polyglyceryl-10; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol and malt
- the surfactant include an anionic surfactant, a nonionic surfactant, a cationic surfactant, an amphoteric surfactant, and a polymer surfactant.
- preferable surfactants include fatty acid salts such as potassium laurate and potassium myristate; alkyl sulfate esters such as sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; Polyoxyethylene alkyl sulfates such as sodium laureth sulfate and triethanolamine laureth sulfate; cocoyl methyl taurine sodium, cocoyl methyl taurine potassium, lauroyl methyl taurine sodium, myristoyl methyl taurine sodium, lauroyl methyl alanine sodium, lauroyl sarcosine sodium, lauroyl sarcosine tri Acyl N-methyl amino acid salts such as ethanolamine and sodium methylalanine sodium, la
- Polyoxyethylene alkyl ethers with various polyoxyethylene addition numbers such as silethylene behenyl ethers), isosteares (polyoxyethylene isostearyl ether) s, octyldecesses (polyoxyethylene octyldodecyl ethers); Ether: Polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester Castor oil and hardened castor oil derivatives such as polyoxyethylene hydrogenated castor oil maleic acid; polyoxyethylene phytosterol; polyoxyethylene cholesterol Polyoxyethylene cholestanol; polyoxyethylene lanolin; polyoxyethylene reduced lanolin; polyoxyethylene / polyoxypropylene cetyl ether, polyoxyethylene / polyoxypropylene 2-decyltetradecyl ether, polyoxy
- Polyglyceryl ethers polyoxyethylene alkylamines; tetrapolyoxyethylene / tetrapolyoxypropylene-ethylenediamine condensates; natural surfactants such as saponins and sophorolipids; polyoxyethylene fatty acid amides; Palm oil fatty acid monoethanolamide (cocamide MEA), palm oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (Lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (partamide MEA), palmitic acid diethanolamide (partamide DEA), palm oil fatty acid methylethanolamide ( Fatty acid alkanolamides such as cocamidomethyl MEA); alkyldimethylamine oxides such as lauramine oxide, cocamamine oxide, stearamine oxide, and behenamine oxide; alkylethoxydimethylamine oxide; polyoxyethylene al
- Nonionic surfactants of silicone, etc .; cationic surfactants include alkyltrimethylammonium chlorides such as behentrimonium chloride, steartrimonium chloride, cetrimonium chloride, lauryltrimonium chloride; stearyltrimonium bromide, etc.
- Alkyltrimethylammonium bromides dialkyldimethylammonium chlorides such as distearyldimonium chloride and dicocodimonium chloride; fatty acid amidoamines and salts thereof such as stearamidepropyldimethylamine and stearamideethyldiethylamine; alkyl ethers such as stearoxypropyldimethylamine Amine and its salts or quaternary salts; ethyl sulfate long chain branched fatty acid (12-31) aminopropylethyldimethylammonium, ethyl Fatty acid amide type quaternary ammonium salts such as lanolin fatty acid aminopropylethyldimethylammonium; polyoxyethylene alkylamines and salts or quaternary salts thereof; alkylamine salts; fatty acid amidoguanidinium salts; alkyl etheraminemonium salts; Benzalkonium salts; benz
- Silicone-based cationic surfactants such as amino-modified silicone, cation-modified silicone, cation-modified and polyether-modified silicone, amino-modified and polyether-modified silicone
- amphoteric surfactant etc N-alkyl-N, N-dimethylamino acid betaines such as lauryl betaine (lauryldimethylaminoacetic acid betaine); fatty acid amide alkyl-N, N-dimethylamino acid betaines such as cocamidopropyl betaine and lauramidopropyl betaine; sodium cocoamphoacetate; Imidazoline-type betaines such as sodium lauroamphoacetate; alkylsulfobetaines such as alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; phosphate-type betaines such as alkyldimethylaminoethanol phosphate; phosphati
- Polymers, thickeners and gelling agents include guar gum, locust bean gum, queens seed, carrageenan, galactan, arabic gum, tara gum, tamarind, far selelain, karaya gum, troarooi, cara gum, tragacanth gum, pectin, pectic acid and sodium Salt such as salt, salt such as alginic acid and sodium salt, mannan; starch such as rice, corn, potato, wheat; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salt, xanthan gum, pullulan, gellan gum, chitin , Chitosan, agar, gypsophila extract, chondroitin sulfate, casein, collagen, gelatin, albumin; methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypro Cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and salts thereof such as
- Acrylic acid / methyl acrylate / methacrylamidopropyltrimethylammonium chloride copolymer such as polyquaternium-47, methacrylic acid choline ester polymer; cationized oligosaccharide, cationized dextran, guar hydroxypropyltri Cationic polysaccharides such as monium chloride; polyethyleneimine; cationic polymers; copolymers of 2-methacryloyloxyethyl phosphorylcholine such as polyquaternium-51 and copolymers of butyl methacrylate; acrylic resin emulsion, polyacrylic acid Polymer emulsions such as ethyl emulsion, polyacrylic alkyl ester emulsion, polyvinyl acetate resin emulsion, natural rubber latex, synthetic latex; nitrocellulose; Tans and various copolymers; Various silicones; Various silicone-based copolymers such as acrylic-silicone graft
- Solvents and propellants include ethanol, 2-propanol (isopropyl alcohol), butanol, isobutyl alcohol and other lower alcohols; propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, isopentyl diol and other glycols Diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, triethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, propylene glycol monoethyl ether, dipropylene glycol monoethyl ether Glycol ethers such as ethylene glycol monoethyl ether Glycol ether esters such as diacetate, diethylene glycol monoethyl ether acetate, propylene glycol monoethyl ether acetate; glycol esters such as dieth
- Antioxidants include tocopherol derivatives such as tocopherol (vitamin E) and tocopherol acetate; BHT, BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and / or derivatives thereof; erythorbic acid and derivatives thereof; Preferred are sulfites such as sodium sulfite; bisulfites such as sodium bisulfite; thiosulfates such as sodium thiosulfate; metabisulfites; thiotaurine, hypotaurine; thioglycerol, thiourea, thioglycolic acid, cysteine hydrochloride As mentioned.
- Preferred examples of the reducing agent include thioglycolic acid, cysteine, cysteamine and the like.
- Preferred examples of the oxidizing agent include hydrogen peroxide water, ammonium persulfate, sodium bromate, percarbonate, and the like.
- preservatives, antibacterial agents, and bactericides include hydroxybenzoic acid such as methylparaben, ethylparaben, propylparaben, and butylparaben, and salts or esters thereof; salicylic acid; sodium benzoate; phenoxyethanol; methylchloroisothiazolinone, methylisothiazo Isothiazolinone derivatives such as linone; imidazolinium urea; dehydroacetic acid and its salts; phenols; halogenated bisphenols such as triclosan, acid amides, quaternary ammonium salts; trichlorocarbanide, zinc pyrithione, benzalkonium chloride, chloride Benzethonium, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; phenol, isopropylphenol, cresol, Mall
- chelating agents include edetate (ethylenediaminetetraacetate) such as EDTA, EDTA2Na, EDTA3Na, and EDTA4Na; hydroxyethylethylenediaminetriacetate such as HEDTA3Na; pentetate (diethylenetriaminepentaacetate); phytic acid; Phosphonic acid and its sodium salt; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, citric acid, alanine, dihydroxyethylglycine, gluconic acid, Ascorbic acid, succinic acid and tartaric acid are preferred.
- edetate ethylenediaminetetraacetate
- HEDTA3Na EDTA3Na
- EDTA4Na hydroxyethylethylenediaminetriacetate
- pentetate diethylenetriaminepentaacetate
- phytic acid
- pH adjusters / acids / alkalis 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, aqueous ammonia, guanidine carbonate, and ammonium carbonate are preferable.
- powders include mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, saucite, biotite, permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, and silicic acid.
- Inorganic salts include sodium chloride-containing salts such as salt, common salt, rock salt, sea salt, natural salt; potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, ammonium chloride; sodium sulfate, aluminum sulfate, Aluminum sulfate / potassium sulfate (alum), aluminum sulfate / ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, iron sulfate, copper sulfate; sodium phosphates such as 1Na, 2Na and 3Na phosphates, phosphoric acid Potassium, calcium phosphates and magnesium phosphates are preferred.
- sodium chloride-containing salts such as salt, common salt, rock salt, sea salt, natural salt
- potassium chloride aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, ammonium chlor
- ultraviolet absorbers examples include paraaminobenzoic acid, paraaminobenzoic acid monoglycerin ester, N, N-dipropoxyparaaminobenzoic acid ethyl ester, N, N-diethoxyparaaminobenzoic acid ethyl ester, and N, N-dimethylparaaminobenzoic acid ethyl ester.
- Benzoic acid ultraviolet absorbers such as esters, N, N-dimethylparaaminobenzoic acid butyl ester, N, N-dimethylparaaminobenzoic acid ethyl ester; Anthranilic acid ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; Salicylic acid And its sodium salt amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, etc.
- Benzophenone series External line absorber 3- (4′-methylbenzylidene) -d, l-camphor, 3-benzylidene-d, l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2′-hydroxy-5- 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole; 2- (2′-hydroxy-5′-methylphenylbenzotriazole; dibenzalazine; dianisoylmethane; 5- (3 , 3-dimethyl-2-norbornylidene) -3-pentan-2-one; dibenzoylmethane derivatives such as 4-t-butylmethoxydibenzoylmethane; octyl triazone; urocanic acid derivatives such as urocanic acid and ethyl urocanate; 2- (2′-hydroxy-5′-methylphenyl) benzotriazole, 1- (3 , 4-Dimethoxyphenyl
- whitening agents include hydroquinone glycosides such as arbutin and ⁇ -arbutin and their esters; ascorbic acid phosphates such as ascorbic acid, sodium ascorbic acid phosphate and magnesium ascorbic acid phosphate, ascorbic acid Ascorbic acid fatty acid esters such as tetraisopalmitic acid ester, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucosides such as ascorbic acid-2-glucoside and fatty acid esters thereof, ascorbic acid sulfate ester, tocopheryl ascorbyl phosphate Ascorbic acid derivatives such as kojic acid, ellagic acid, tranexamic acid and its derivatives, ferulic acid and its derivatives, placenta extract, glutathione, oryzanol, butylreso Shinoru, oil-soluble Kamomiraekisu, oil-soluble licorice extract,
- Vitamins and their derivatives include vitamin A such as retinol, retinol acetate, retinol palmitate; thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, Flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinic acid such as nicotinic acid amide / benzyl nicotinate, vitamin B group such as choline; vitamin C such as ascorbic acid and its sodium salt; vitamin D; ⁇ , Vitamin E such as ⁇ , ⁇ , and ⁇ -tocopherol; other vitamins such as pantothenic acid and biotin; ascorbic acid phosphates such as ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt, Ascorbic acid fatty acid esters
- Plant growth and tinctures such as assembly extract, red pepper tincture, ginger tincture, ginger extract, cantalis tincture; capsaicin, nonyl acid valenylamide, gingeron, ictamol, tannic acid Borneol, cyclandrate, cinnarizine, trazoline, acetylcholine, verapamil, cephalanthin, ⁇ -oryzanol, vitamin E and derivatives such as tocopherol / nicotinic acid tocopherol, ⁇ -oryzanol, nicotinic acid, nicotinic acid amide, nicotinic acid benzyl ester, Inositol hexanicotinate, derivatives such as nicotine alcohol, allantoin, photosensitive element 301, photosensitive element 401, capronium chloride, pentadecanoic acid monoglyceride, flavonol Derivatives, stigmasterol or stigmasterol and its glycoside
- hormones include estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone and the like.
- Other remedies such as anti-wrinkle agents, anti-aging agents, squeeze agents, cooling sensations, warming sensation agents, wound healing promoters, irritation relievers, analgesics, cell activators include retinols, retinoic acids, retinoin Acid tocopheryl; derivatives such as lactic acid, glycolic acid, gluconic acid, fruit acid, salicylic acid and glycosides / esterified products thereof, ⁇ - or such as hydroxycapric acid, long chain ⁇ -hydroxy fatty acid, long chain ⁇ -hydroxy fatty acid cholesteryl ⁇ -hydroxy acids and derivatives thereof; ⁇ -aminobutyric acid, ⁇ -amino- ⁇ -hydroxybutyric acid; carnitine; carnosine; creatine; ceramides, sphingosines; caffeine, xant
- Antioxidant / active oxygen scavengers include catechins; flavones such as quercetin; isoflavones; gallic acid and ester sugar derivatives; polyphenols such as tannin, sesamin, protoanthocyanidin, chlorogenic acid, apple polyphenol; rutin and glycosides, etc.
- antipruritic agents examples include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, substance-P inhibitor, and the like.
- exfoliating / dissolving agent examples include salicylic acid, sulfur, resorcin, selenium sulfide, pyridoxine and the like.
- antiperspirants examples include chlorohydroxyaluminum, aluminum chloride, zinc oxide, zinc paraphenol sulfonate, and the like.
- Examples of the refreshing agent include menthol and methyl salicylate.
- astringents include citric acid, tartaric acid, lactic acid, aluminum sulfate / potassium, and tannic acid.
- Enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, protease, and the like.
- Preferred nucleic acids include ribonucleic acid and its salts, deoxyribonucleic acid and its salts, and adenosine triphosphate disodium.
- Anti-inflammatory and anti-inflammatory agents include glycyrrhizic acid and its derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, ketoprofen, ibuprofen, diclofenac, loxoprofen, celecoxib, infliximab, etanercept, zinc oxide, hydroxanthone acetate Prednisone, difedramine hydrochloride, chlorpheniramine maleate; plant extracts such as peach leaf extract and persimmon leaf extract are preferable.
- Anti-asthma, anti-chronic obstructive pulmonary disease, anti-allergy, immunomodulators include aminophylline, theophylline, steroids (fluticasone, beclomethasone, etc.), leukotriene antagonists, thromboxane inhibitors, intal, ⁇ 2-stimulant (Formoterol, salmeterol, albuterol, tulobuterol, clenbuterol, epinephrine, etc.), tiotropium, ipratropium, dextromethorphan, dimemorphan, bromhexine, tranilast, ketotifen, azelastine, cetirizine, chlorpheniramine, polyquitolsine, Preferred examples include cytokine regulators, interferons, omalizumab, and protein / antibody preparations.
- Preferred examples of the anti-infective and antifungal agents include oseltamivir, zanamivir, and itraconazole.
- cosmetic raw material standards cosmetic ingredient-specific combination ingredient standards, Japan Cosmetic Industry Association ingredient display name list, INCI dictionary (The International Cosmetic Ingredients and Handbooks), quasi-drug ingredients standards, Japanese pharmacopoeia, pharmaceutical additive standards Ingredients listed in the Food Addendum, etc., and the international patent classification IPC described in Japan and other foreign patent gazettes and patent publications (including publications and republications) belonging to the A61K7 and A61K8 classifications It is possible to contain known cosmetic ingredients, pharmaceutical ingredients, food ingredients, etc., in known combinations, blending ratios and blending amounts.
- the solid base material for external use of the skin of the present invention comprises a lipid peptide compound comprising at least one of the compounds represented by the formulas (1) to (3) or a pharmaceutically usable salt thereof, a surfactant and water. Further, if desired, it can be produced by mixing and stirring with heating using 1,2-alkanediol or glycerin, fatty acid, oily base material, organic acid and other additives, and then standing to cool. In this production process, the aqueous composition of the present invention can be produced as described later.
- the solid base for external use of the present invention is produced by the following steps as an example. a) Step of blending the lipid peptide compound, surfactant and water, and preparing a solution or dispersion by heating b) Adding the solution or dispersion to water, and having a temperature of room temperature to less than 100 ° C. Step c) Heating at temperature Cooling with stirring until the temperature is lower than the temperature in the heating step, and then allowing to stand and cool to form a gel-like solid (solid base for external skin).
- 1,2-alkanediol or glycerin, fatty acid, oily base, organic acid, polyethylene glycol and other additives may be added in the step of preparing the solution or dispersion in step a), or in step b).
- You may add beforehand to the water which adds a solution or a dispersion liquid.
- water is 60 mass% or more and less than 95 mass% with respect to the total mass of the obtained skin external solid base material.
- water is 50 mass% or more and less than 80 mass% with respect to the total mass of the obtained solution or dispersion.
- the heating temperature in the step a) and the step b) is preferably 50 ° C. to 90 ° C., more preferably 60 ° C. to 90 ° C., for example 80 ° C., and stirring is preferably performed while heating.
- the time of heating and stirring in each step at this time varies depending on the type of lipid peptide compound used, the surfactant and other components, and the blending amount thereof, but can usually be dissolved and dispersed in about 5 to 50 minutes. .
- cooling is performed with stirring until the liquid temperature is lower than the temperature in step b) (step c).
- the cooling temperature is, for example, room temperature to 80 ° C., room temperature to 60 ° C., or room temperature to 40 ° C.
- a lipid peptide compound comprising at least one of the compounds represented by the formulas (1) to (3) or a pharmaceutically usable salt thereof, and a surfactant And water are mixed and heated to prepare a solution or dispersion.
- 1,2-alkanediol or glycerin and / or fatty acid may be added if desired, and an oily base material, organic acid, polyethylene glycol and other additives are added. You can also.
- an aqueous composition can be obtained by cooling this solution or dispersion.
- the heating temperature is preferably 50 ° C. to 90 ° C., more preferably 60 ° C. to 90 ° C., for example 80 ° C. Moreover, it is preferable to stir at the time of a heating.
- the heating (stirring) time varies depending on the lipid peptide compound used, the type of surfactant and other components, and the blending amount thereof, but it is usually about 5 to 50 minutes, so that the blended components dissolve and disperse.
- a dissolved or dispersed solution is obtained.
- the obtained solution or dispersion is preferably cooled with stirring until the temperature is lower than the heating temperature, for example, room temperature to 80 ° C., room temperature to 60 ° C., or room temperature to 40 ° C., and then the stirring is stopped.
- aqueous composition thus obtained is useful as a premix for the preparation of a solid base for external use on the skin, and by adding water, other active ingredients, etc. to the composition as described later, It is possible to prepare the material easily.
- a solid base material for external application to skin can be produced, for example, by the following steps 1) to 3). 1) A step of heating the aqueous composition at a temperature of room temperature to less than 100 ° C. 2) A step of adding and mixing the heated aqueous composition to an aqueous phase heated at a temperature of room temperature to less than 100 ° C., and 3) a step of cooling the resulting mixture to form a gel.
- the aqueous phase contains water, may further contain an oily base material, and may contain 1,2-alkanediol or glycerin, fatty acid, organic acid, polyethylene glycol and other additives.
- an organic acid blended solid external base material can be produced, for example, by the following steps 4) to 7).
- a step of heating the aqueous composition at a temperature of room temperature to less than 100 ° C. 5) A step of adding and mixing the heated aqueous composition to an aqueous phase heated at a temperature of room temperature to less than 100 ° C., 6) A step of cooling the obtained mixture to form a gel, and 7) A step of adding a mixture of water and an organic acid to the mixture and further mixing in the middle of the cooling process.
- the aqueous phase contains water, may further contain an oily base material, and may contain 1,2-alkanediol or glycerin, fatty acid, polyethylene glycol and other additives.
- the heating temperature of the aqueous composition in the steps 1) and 4) is preferably 50 ° C. to 90 ° C., more preferably 60 ° C. to 90 ° C., for example 70 ° C. or 80 ° C.
- This step is preferably carried out with stirring.
- the time of heating (stirring) in each step at this time is usually about 5 to 50 minutes, although it varies depending on the type of lipid peptide compound, surfactant and other components contained in the aqueous composition, and their blending amount. .
- the heating temperature of the aqueous phase is preferably 50 ° C. to 90 ° C., more preferably 60 ° C.
- the heating of the aqueous phase is preferably carried out with stirring, particularly when other components such as an oily substrate are included. If the aqueous phase contains an oily base material, further 1,2-alkanediol or glycerin, fatty acid, polyethylene glycol and other additives, it usually takes about 5 to 50 minutes until they are uniformly dissolved and dispersed. It is preferable to carry out heating (stirring).
- the heating temperature of the aqueous phase may be the same temperature as the heating temperature of the aqueous composition.
- the mixture obtained in the previous step is cooled to form a gel.
- the mixture may be cooled with stirring.
- the skin external solid base contains an organic acid such as ascorbic acid
- a step of adding a mixture of water and organic acid to the mixture and further mixing Including is preferable because it can achieve uniform mixing, preferably by setting the temperature to the same level as the mixture to be added.
- the mixed solution may contain 1,2-alkanediol or glycerin, an oily base material, a fatty acid, polyethylene glycol and other additives, if desired, at an appropriate temperature until they are uniformly dissolved and dispersed. Heating (stirring) may be performed at For example, when the liquid temperature of the mixture reaches about 60 ° C.
- a mixed solution of water and organic acid having a liquid temperature of about 60 ° C. is added to the mixture and further mixed to form a system.
- the gel solid base material for external use on the skin
- the amount of water is preferably 60% by mass or more and less than 95% by mass with respect to the total mass of the external base material for skin.
- the obtained solid was dissolved in 120 g of tetrahydrofuran and 60 g of acetonitrile, heated to 60 ° C., stirred for 1 hour, cooled, and filtered.
- the solid obtained here was washed with 120 g of water, dried under reduced pressure after filtration, and 26.9 g (yield 65) of white crystals of N-palmitoyl-Gly-His free form (hereinafter also simply referred to as “Pal-GH”). %).
- each component of the A phase is sample tube No. Weighed to 5.
- the weighed phase A was heated to 70 ° C. or higher and dissolved uniformly.
- another sample tube No. 5 was weighed 5.0 g of water as B phase and heated to 70 ° C. or higher. Thereafter, the A phase was added to the B phase, mixed in a heated state and stirred for about 30 seconds, and then allowed to stand and cool.
- each component of the A phase is sample tube No. Weighed to 5.
- the weighed phase A was heated to 70 ° C. or higher and dissolved uniformly.
- another sample tube No. In FIG. 5 each component of the B phase was weighed and heated to 70 ° C. or higher.
- the A phase was added to the B phase, mixed in a heated state, stirred for about 30 seconds, and then cooled with stirring until reaching 60 ° C. After 60 ° C., standing and cooling was performed.
- the breaking strength was measured in the same manner as described above (breaking strength measurement method). The obtained results are shown in Table 2.
- the skin external solid substrates of Examples 1 to 9 have a breaking strength: 0.42 to 1.40 ⁇ 10 5 Pa, and are particularly obtained as stick-like substrates.
- Comparative Example 1 which does not contain 1,2-alkanediol and surfactant and Comparative Example 2 which does not contain a surfactant cannot detect the breaking stress, and the result is that the strength as a stick-like substrate is insufficient. It became.
- each component of the A phase is sample tube No. Weighed to 5.
- the weighed phase A was heated to 70 ° C. or higher and dissolved uniformly.
- another sample tube No. In FIG. 5 each component of the B phase was weighed and heated to 70 ° C. or higher.
- the A phase was added to the B phase, mixed in a heated state, stirred for about 30 seconds, and then cooled with stirring until reaching 60 ° C. After 60 ° C., standing and cooling was performed.
- the glycerin in the B phase of Example 14 is added as a humectant / sensitivity improver.
- the breaking strength was measured in the same manner as described above (breaking strength measurement method). The obtained results are shown in Table 3.
- the skin external solid substrates of Examples 10 to 15 had a high strength of breaking strength: 1.8 to 5.2 ⁇ 10 5 Pa.
- each component of the A phase was changed to Marum sample tube No. 3 was weighed.
- the weighed phase A was heated in a water bath (set temperature 85 ° C.) and dissolved uniformly.
- another Marum sample tube No. with a stirrer tip was inserted.
- Each component of Phase B was weighed in 5 and heated in a water bath (set temperature 85 ° C.).
- a phase was added to B phase, and stirring cooling was started until the liquid temperature became about 60 degreeC.
- Each component of phase C was weighed into 5 and heated so that the liquid temperature was about 60 ° C.
- Example 16 the solid base materials for external application of Example 16 and Example 17 were 5% by mass of ascorbic acid (Example 16) and further 10% with respect to the total mass of the solid base material for external skin. % (Example 17), even when it was added, the fracture strength was as high as 2.1 to 2.4 ⁇ 10 5 Pa.
- each component of the A phase was changed to Marum sample tube No. 7 was weighed.
- the weighed phase A was heated and stirred in a water bath (set temperature 80 ° C.) until the liquid temperature reached 80 ° C., and dissolved uniformly.
- a magnetic stirrer was used for stirring.
- another Marum sample tube No. with a stirrer tip was inserted.
- the ingredients of Phase B were weighed in 7 and heated and stirred in a water bath (set temperature 80 ° C.) until the liquid temperature reached 80 ° C.
- a phase was added to B phase, and heating and stirring were continued for 1 minute at the set temperature.
- the sample tube containing the A phase + B phase was removed from the water bath, and cooling was started.
- the magnetic stirrer was removed simultaneously with the start of cooling, and the subsequent stirring was performed manually using a spatula until the liquid temperature reached 60 ° C.
- prepare a metal container inner diameter ⁇ 9.5 mm, lipstick container made by HIDAN Co., Ltd., with the lid attached so as to cover the container body and the whole body).
- a covered and sealed sample was prepared.
- Example 18 blended with polyethylene glycol has a low mass loss rate and high stability over time as compared with Reference Examples 1 to 3. It was.
- each component of the A phase is sample tube No. Weighed to 5.
- the weighed phase A was heated to 70 ° C. or higher and dissolved uniformly.
- another sample tube No. 5 was weighed 5.0 g of water as B phase and heated to 70 ° C. or higher.
- the A phase was added to the B phase, mixed in a heated state and stirred for about 30 seconds, and then allowed to stand and cool.
- the breaking strength was measured in the same manner as described above (breaking strength measurement method). The results obtained are shown in Table 6.
- the solid base materials for external application of Examples 19 to 22 have a breaking strength: 0.45 to 2.01 ⁇ 10 5 Pa, and particularly have the strength required as a stick base material.
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Abstract
Description
水性固形状組成物としては従来、水と脂肪酸石鹸と油分と粉末を含有する固形状水中油型メーキャップ化粧料(特許文献1)、アルキル及び/またはアルケニルオリゴグリコシド、油性物質、及びノニオン性乳化剤を含有するスティック状の水性化粧品(特許文献2)等が提案されている。
本発明は上記の事情に基いてなされたものであり、その解決しようとする課題は、スティック状の基材等に使用できる破断強度が高い皮膚外用固形基材を提供することである。
第2観点として、1,2-アルカンジオール又はグリセリンを更に含む、第1観点に記載の皮膚外用固形基材に関する。
第3観点として、少なくとも一種の脂肪酸を更に含む、第1観点又は第2観点に記載の皮膚外用固形基材に関する。
第4観点として、少なくとも一種の油性基剤を更に含む、第1観点乃至第3観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第5観点として、少なくとも一種の有機酸を更に含む、第1観点乃至第4観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第6観点として、前記界面活性剤が、エチレングリコールアルキルエーテル、リン脂質、ポリグリセリン脂肪酸エステル及びポリオキシエチレンポリオキシプロピレンアルキルエーテルからなる群から選択される1種類以上の化合物である、第1観点乃至第5観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第7観点として、前記脂肪酸がステアリン酸である、第3観点乃至第6観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第8観点として、前記有機酸がアスコルビン酸である、第5観点乃至第7観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第9観点として、ポリエチレングリコールを更に含有する、第1観点乃至第8観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第10観点として、化粧品又は医薬用である、第1観点乃至第9観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第11観点として、スティック状である、第1観点乃至第10観点のうち何れか一項に記載の皮膚外用固形基材に関する。
第12観点として、界面活性剤及び水と、前記式(1)乃至式(3)で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなる脂質ペプチド型化合物とを含む、水性組成物に関する。
第13観点として、1,2-アルカンジオール又はグリセリンを更に含む、第12観点に記載の水性組成物。
第14観点として、少なくとも一種の脂肪酸を更に含む、第12観点又は第13観点に記載の水性組成物に関する。
第15観点として、前記界面活性剤が、エチレングリコールアルキルエーテル、リン脂質、ポリグリセリン脂肪酸エステル及びポリオキシエチレンポリオキシプロピレンアルキルエーテルからなる群から選択される1種類以上の化合物である、第12観点乃至第14観点のうち何れか一項に記載の水性組成物に関する。
第16観点として、皮膚外用固形基材の調製のためのプレミックスである、第12観点乃至第15観点のうち何れか一項に記載の水性組成物に関する。
第17観点として、第12観点乃至第16観点のうち何れか一項に記載の水性組成物を室温以上100℃未満の温度で加熱する工程、
室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、及び
得られた混合物を冷却し、ゲルを形成させる工程、
を含む第1観点に記載の皮膚外用固形基材の製造方法に関する。
第18観点として、前記水相が少なくとも一種の油性基材を含む、第17観点に記載の製造方法に関する。
第19観点として、前記水相がポリエチレングリコールを含む、第17観点に記載の製造方法に関する。
第20観点として、第12観点乃至第16観点のうち何れか一項に記載の水性組成物を室温以上100℃未満の温度で加熱する工程、
室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、
得られた混合物を冷却し、ゲルを形成させる工程、及び
前記冷却過程の中途において、前記混合物に水と有機酸の混合液を添加し、さらに混合する工程、
を含む第5観点に記載の皮膚外用固形基材の製造方法に関する。
第21観点として、前記水相が少なくとも一種の油性基材を含む、第20観点に記載の製造方法に関する。
また本発明は、およそ90質量%もの高い含水量を達成可能なゲル状の基材であり、また油性成分も同時に配合可能な皮膚外用固形基材を提供できる。
さらに本発明の皮膚外用固形基材において添加剤として含まれる各主成分は食品や化粧品、医薬品の添加剤として汎用の添加剤である。
すなわち、本発明の皮膚外用固形基材は生体安全性が高く、特に、医用材料、或いは化粧品用材料等において要求される高い安全性の観点からみて、上記用途において非常に有用である。
その上本発明の皮膚外用固形基材は、ヒトの肌等に適用した場合に清涼感がよく、また折れたり変形したりせず、伸びがよい基材となることが期待されるため、化粧品用基材や医薬用基材として、特にスティック状の基材として非常に有用である。
そして本発明は上記水性組成物を用いることにより、特に、アスコルビン酸のような有機酸を多量に配合した場合においても、スティック状基材として求められる強度を有するゲル状の皮膚外用固形基材を提供できる。
また本発明は、前記界面活性剤、水、前記脂質ペプチド型化合物を含み、所望により1,2-アルカンジオール又はグリセリン、脂肪酸を含み、さらに油性基材、有機酸、ポリエチレングリコール、その他添加剤を含み得る水性組成物も対象とする。
本発明の皮膚外用固形基材は化粧品又は医薬品向けに好適であり、特にスティック状の基材として適用され得る。なお本発明においてスティック状基材とは、棒状の形状を維持し且つ皮膚等に適用可能となる強度を有する棒状の基材を言及する。スティック基材として求められる強度としては、例えば破断強度:0.4×105Pa~8.0×105Paであり、好ましくは1.0×105Pa~7.0×105Paであり、より好ましくは1.0×105Pa~6.0×105Paである。
以下、各構成成分について説明する。
本発明の皮膚外用固形基材又は水性組成物において用いる脂質ペプチド型化合物としては、下記式(1)乃至式(3)で表される化合物(脂質ペプチド)又はその薬学的に使用可能な塩(疎水性部位である脂質部と親水性部位であるペプチド部とを有する低分子化合物)を用いることができる。
R1は及び隣接するカルボニル基で構成される脂質部(アシル基)の具体例としては、ラウロイル基、ドデシルカルボニル基、ミリストイル基、テトラデシルカルボニル基、パルミトイル基、マルガロイル基、オレオイル基、エライドイル基、リノレオイル基、ステアロイル基、バクセノイル基、オクタデシルカルボニル基、アラキドイル基、エイコシルカルボニル基、ベヘノイル基、エルカノイル基、ドコシルカルボニル基、リグノセイル基、ネルボノイル基等を挙げることができ、特に好ましいものとして、ラウロイル基、ミリストイル基、パルミトイル基、マルガロイル基、ステアロイル基、オレオイル基、エライドイル基及びベヘノイル基が挙げられる。
上記炭素原子数1若しくは2の分岐鎖を有し得る炭素原子数1乃至4のアルキル基とは、主鎖の炭素原子数が1乃至4であり、かつ炭素原子数1若しくは2の分岐鎖を有し得るアルキル基を意味し、その具体例としては、メチル基、エチル基、n-プロピル基、i-プロピル基、n-ブチル基、i-ブチル基、sec-ブチル基又はtert-ブチル基などが挙げられる。
上記R2は好ましくは、水素原子、又は炭素原子数1の分岐鎖を有し得る炭素原子数1乃至3のアルキル基であり、より好ましくは水素原子である。
炭素原子数1の分岐鎖を有し得る炭素原子数1乃至3のアルキル基とは、主鎖の炭素原子数が1乃至3であり、かつ炭素原子数1の分岐鎖を有し得るアルキル基を意味し、その具体例としては、メチル基、エチル基、n-プロピル基、i-プロピル基、i-ブチル基又はsec-ブチル基などが挙げられ、好ましくはメチル基、i-プロピル基、i-ブチル基又はsec-ブチル基である。
上記R3を表す-(CH2)n-X基において、Xは好ましくはアミノ基、グアニジノ基、カルバモイル基(-CONH2基)、ピロール基、イミダゾール基、ピラゾール基又はインドール基であり、より好ましくはイミダゾール基である。また、上記-(CH2)n-X基において、nは好ましくは1又は2であり、より好ましくは1である。
従って、上記-(CH2)n-基は、好ましくはアミノメチル基、2-アミノエチル基、3-アミノプロピル基、4-アミノブチル基、カルバモイルメチル基、2-カルバモイルエチル基、3-カルバモイルブチル基、2-グアニジノエチル基、3-グアニジノブチル基、ピロールメチル基、4-イミダゾールメチル基、ピラゾールメチル基、又は3-インドールメチル基を表し、より好ましくは4-アミノブチル基、カルバモイルメチル基、2-カルバモイルエチル基、3-グアニジノブチル基、4-イミダゾールメチル基又は3-インドールメチル基を表し、さらに好ましくは4-イミダゾールメチル基である。
上記式(2)において、R5乃至R7は、それぞれ独立して、水素原子、又は炭素原子数1若しくは2の分枝鎖を有し得る炭素原子数1乃至4のアルキル基、又は-(CH2)n-X基を表し、且つR5乃至R7のうち少なくとも一つ以上が-(CH2)n-X基を表す。nは1乃至4の数を表し、Xはアミノ基、グアニジノ基、-CONH2基、又は窒素原子を1乃至3個有し得る5員環式基若しくは6員環式基、又は5員環と6員環から構成される縮合複素環式基を表す。ここでR5乃至R7の好ましい具体例としては、前出のR2及びR3で定義したものと同じ基が挙げられる。
上記式(3)において、R9乃至R12は、それぞれ独立して、水素原子、又は炭素原子数1若しくは2の分枝鎖を有し得る炭素原子数1乃至4のアルキル基、又は-(CH2)n-X基を表し、且つR9乃至R12のうち少なくとも一つ以上が-(CH2)n-X基を表す。nは1乃至4の数を表し、Xはアミノ基、グアニジノ基、-CONH2基、又は窒素原子を1乃至3個有し得る5員環式基若しくは6員環式基、又は5員環と6員環から構成される縮合複素環式基を表す。ここでR9乃至R12の好ましい具体例としては、前出のR2及びR3で定義したものと同じ基が挙げられる。
本発明において、脂質ペプチド型化合物の配合量は、得られる水性組成物の総質量に対して、例えば5乃至20質量%、好ましくは、10乃至20質量%である。
なお本発明において用いられる脂質ペプチド型化合物は、上記式(1)乃至式(3)で表される化合物(脂質ペプチド)又はその薬学的な使用可能な塩のうちの少なくとも一種からなり、ヒドロゲル化剤としてこれら化合物を単独で、或いは二種以上を組み合わせて用いることができる。
本発明の皮膚外用固形基材又は水性組成物において使用する界面活性剤として、分子内に親水部と疎水部を有し、かつ該親水部がベタイン構造を有する化合物(以下、ベタイン系化合物とも称する)、エチレングリコールアルキルエーテル、ポリグリセリン脂肪酸エステル、或いはポリオキシエチレンポリオキシプロピレンアルキルエーテルを好適に用いることができる。
また、上記ベタイン系化合物として、ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルセリン、ホスファチジルイノシトール、ホスファチジルグリセロール、ジホスファチジルグリセロール(カルジオリピン)、ホスファチジン酸などのグリセロリン脂質;リゾホスファチジルコリン(リゾレシチン)、リゾホスファチジルエタノールアミン、リゾホスファチジルセリン、リゾホスファチジルイノシトール、リゾホスファチジルグリセロール、リゾホスファチジン酸などのリゾグリセロリン脂質;スフィンゴミエリンなどのスフィンゴリン脂質;およびこれらの水素添加物などが挙げられる。これらのリン脂質は、大豆、卵黄などの動植物由来のものでもよく、化学的もしくは酵素的方法により合成されたものでもよい。
上記ベタイン系化合物の中でも、好ましくは、ラウリルジメチルアミノ酢酸ベタイン、ラウリン酸アミドプロピルベタイン、ラウリルヒドロキシスルホベタイン、ステアリルベタイン、リゾホスファチジルコリン(リゾレシチン)、リゾホスファチジルエタノールアミン、リゾホスファチジルセリン、リゾホスファチジルイノシトール、リゾホスファチジルグリセロール、リゾホスファチジン酸などが挙げられ、さらに好ましくは、リゾホスファチジルコリン(リゾレシチン)が挙げられる。
このような界面活性剤としては、例えばイソステアリン酸ソルビタン、ステアレス-8、ベヘネス-10、ラウレス-5、セテス-7、オレス-8、イソステアリン酸PEG-8グリセリル、コレス-10、イソステアリン酸PEG-10BG、トリイソステアリン酸PEG-30グリセリル、トリイソステアリン酸PEG-30グリセリル、トリオレイン酸PEG-30グリセリル、トリイソステアリン酸PEG-30トリメチロールプロパン、ラウリン酸PEG-30水添ヒマシ油、PCAイソステアリン酸PEG-30水添ヒマシ油、オクチルドデセス-10、ジラウリン酸PEG-12、テトラオレイン酸ソルベス-40、ジイソステアリン酸ポリグリセリル-10、ジイソステアリン酸PEG-20グリセリル、イソステアリン酸PEG-8、イソステアリン酸PEG-10グリセリル、トリイソステアリン酸PEG-60水添ヒマシ油、PPG-2-デセス-7、オレス-10、水添ダイマージリノレス-20、ヤシ脂肪酸ソルビタン、イソステアレス-10、ステアレス-11、トリミリスチン酸PEG-30トリメチロールプロパン、イソステアリン酸PEG-40水添ヒマシ油、イソステアリン酸PEG-40水添ヒマシ油、PCAイソステアリン酸PEG-40水添ヒマシ油、ラウレス-7、イソセテス-10、セテス-10、イソステアリン酸PEG-10、ステアリン酸PEG-10、オレイン酸PEG-10、ステアリン酸PEG-10グリセリル、オレス-12、デシルテトラデセス-15、コレス-15、ジラウリン酸PEG-16、PEG-30水添ヒマシ油、トリイソステアリン酸PEG-40グリセリル、トリオレイン酸PEG-40グリセリル、トリイソステアリン酸PEG-40トリメチロールプロパン、ラウリン酸PEG-40水添ヒマシ油、ラウリン酸PEG-12などが挙げられる。
本発明において、界面活性剤の配合量は、得られる水性組成物の総質量に対して、例えば1乃至20質量%、好ましくは、2乃至10質量%である。
なお本発明において用いられる界面活性剤は、上述の界面活性剤群の少なくとも一種であり、これら界面活性剤を単独で、或いは二種以上を組み合わせて用いることができる。
本発明の皮膚外用固形基材又は水性組成物には、1,2-アルカンジオールを含んでいてもよい。1,2-アルカンジオールは前記脂質ペプチド型化合物の溶解性を促進させる働きをもつ。
前記1,2-アルカンジオールの具体例としては、1,2-ペンタンジオール、1,2-ヘキサンジオール、1,2-オクタンジオール及び1,2-デカンジオールなどが挙げられる。好ましくは、1,2-ペンタンジオール、1,2-ヘキサンジオール、1,2-オクタンジオールが挙げられる。さらに好ましくは、1,2-ペンタンジオール又は1,2-ヘキサンジオールである。本発明で使用する1,2-アルカンジオールは上述の1,2-アルカンジオール群の少なくとも一種であり、これら1,2-アルカンジオールを単独で、或いは二種以上を組み合わせて用いることができる。
また本発明の皮膚外用固形基材又は水性組成物では、上記1,2-アルカンジオールに加えて、グリセリンも、前記脂質ペプチド型化合物の溶解性を促進させる働きを有するものとして好適に使用され得る。なお前述の界面活性剤には、市販品においてグリセリンを溶剤として含む製品もあり、この市販品を使用した場合に成分として含まれるグリセリンも同様に脂質ペプチド型化合物の溶解性を促進させるように作用する。
本発明において、1,2-アルカンジオール又はグリセリンの配合量は、得られる皮膚外用固形基材の総質量に対して、例えば1乃至20質量%、好ましくは、1乃至10質量%、より好ましくは1乃至5質量%である。
本発明において、1,2-アルカンジオール又はグリセリンの配合量は、得られる水性組成物の総質量に対して、例えば2乃至20質量%、好ましくは、2乃至10質量%である。
本発明の皮膚外用固形基材又は水性組成物は、脂肪酸をさらに含んでいてもよい。本発明において使用される脂肪酸は、好ましくは炭素原子数10乃至20の飽和脂肪酸及び不飽和脂肪酸並びにそれら脂肪酸の塩からなる群から選択される少なくとも1種であり、例えば脂肪酸としてはカプリン酸、ウンデカン酸、ラウリン酸、トリデカン酸、ミリスチン酸、ペンタデカン酸、パルミチン酸、マルガリン酸、ステアリン酸が挙げられる。さらに好ましくは、カプリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸が挙げられ、なかでもステアリン酸が好ましい。
本発明において、使用される脂肪酸の配合量は、得られる皮膚外用固形基材の総質量に対して、例えば0.1乃至2.0質量%、好ましくは0.2乃至1.0質量%である。
本発明において、脂肪酸の配合量は、得られる水性組成物の総質量に対して、例えば0.5乃至5質量%、好ましくは、0.5乃至3質量%である。
なお本発明において用いられる脂肪酸は、上記脂肪酸群から選択される少なくとも1種であり、これら脂肪酸を単独で、或いは二種以上を組み合わせて用いることができる。
本発明の皮膚外用固形基材はさらに油性基材を含んでいてもよい。また本発明の水性組成物においても油性基材を含み得る。本発明において使用される油性基剤としては、セタノール、ミリスチルアルコール、オレイルアルコール、ラウリルアルコール、セトステアリルアルコール、ステアリルアルコール、アラキルアルコール、ベヘニルアルコール、ホホバアルコール、キミルアルコール、セラキルアルコール、バチルアルコール、ヘキシルデカノール、イソステアリルアルコール、2-オクチルドデカノール、ダイマージオール等の高級(多価)アルコール類;ベンジルアルコール等のアラルキルアルコール及びその誘導体;イソステアリン酸、ベヘン酸、ウンデシレン酸、12-ヒドロキシステアリン酸、パルミトオレイン酸、オレイン酸、リノール酸、リノレイン酸、エルカ酸、ドコサヘキサエン酸、エイコサペンタエン酸、イソヘキサデカン酸、アンテイソヘンイコサン酸、長鎖分岐脂肪酸、ダイマー酸、水素添加ダイマー酸等;流動パラフィン(ミネラルオイル)、重質流動イソパラフィン、軽質流動イソパラフィン、α-オレフィンオリゴマー、ポリイソブテン、水添ポリイソブテン、ポリブテン、スクワラン、オリーブ由来スクワラン、スクワレン、ワセリン、固形パラフィン等の炭化水素類;キャンデリラワックス、カルナウバワックス、ライスワックス、木ろう、みつろう、モンタンワックス、オゾケライト、セレシン、パラフィンワックス、マイクロクリスタリンワックス、ペトロラタム、フィッシャートロプシュワックス、ポリエチレンワックス、エチレン・プロピレンコポリマー等のワックス類;ヤシ油、パーム油、パーム核油、サフラワー油、オリーブ油、ヒマシ油、アボカド油、ゴマ油、茶油、月見草油、小麦胚芽油、マカデミアナッツ油、ヘーゼルナッツ油、ククイナッツ油、ローズヒップ油、メドウフォーム油、パーシック油、ティートリー油、ハッカ油、トウモロコシ油、ナタネ油、ヒマワリ油、小麦胚芽油、アマニ油、綿実油、大豆油、落花生油、コメヌカ油、カカオ脂、シア脂、水素添加ヤシ油、水素添加ヒマシ油、ホホバ油、水素添加ホホバ油等の植物油脂類;牛脂、乳脂、馬脂、卵黄油、ミンク油、タートル油等の動物性油脂類;鯨ロウ、ラノリン、オレンジラッフィー油等の動物性ロウ類;液状ラノリン、還元ラノリン、吸着精製ラノリン、酢酸ラノリン、酢酸液状ラノリン、ヒドロキシラノリン、ポリオキシエチレンラノリン、ラノリン脂肪酸、硬質ラノリン脂肪酸、ラノリンアルコール、酢酸ラノリンアルコール、酢酸(セチル・ラノリル)エステル等のラノリン類;コレステロール、ジヒドロコレステロール、ラノステロール、ジヒドロラノステロール、フィトステロール、コール酸等のステロール類;サポゲニン類;サポニン類;酢酸コレステリル、ノナン酸コレステリル、ステアリン酸コレステリル、イソステアリン酸コレステリル、オレイン酸コレステリル、N-ラウロイル-L-グルタミン酸ジ(コレステリル/ベヘニル/オクチルドデシル)、N-ラウロイル-L-グルタミン酸ジ(コレステリル/オクチルドデシル)、N-ラウロイル-L-グルタミン酸ジ(フィトステリル/ベヘニル/オクチルドデシル)、N-ラウロイル-L-グルタミン酸ジ(フィトステリル/オクチルドデシル)、N-ラウロイルサルコシンイソプロピル等のアシルサルコシンアルキルエステル、12-ヒドロキシステアリン酸コレステリル、マカデミアナッツ油脂肪酸コレステリル、マカデミアナッツ油脂肪酸フィトステリル、イソステアリン酸フィトステリル、軟質ラノリン脂肪酸コレステリル、硬質ラノリン脂肪酸コレステリル、長鎖分岐脂肪酸コレステリル、長鎖α-ヒドロキシ脂肪酸コレステリル等のステロールエステル類;リン脂質・コレステロール複合体、リン脂質・フィトステロール複合体等の脂質複合体;ミリスチン酸オクチルドデシル、ミリスチン酸ヘキシルデシル、イソステアリン酸オクチルドデシル、パルミチン酸セチル、パルミチン酸オクチルドデシル、オクタン酸セチル、オクタン酸ヘキシルデシル、イソノナン酸イソトリデシル、イソノナン酸イソノニル、イソノナン酸オクチル、イソノナン酸イソトリデシル、ネオペンタン酸イソデシル、ネオペンタン酸イソトリデシル、ネオペンタン酸イソステアリル、ネオデカン酸オクチルドデシル、オレイン酸オレイル、オレイン酸オクチルドデシル、リシノレイン酸オクチルドデシル、ラノリン脂肪酸オクチルドデシル、ジメチルオクタン酸ヘキシルデシル、エルカ酸オクチルドデシル、イソステアリン酸硬化ヒマシ油、オレイン酸エチル、アボカド油脂肪酸エチル、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、パルミチン酸オクチル、イソステアリン酸イソプロピル、ラノリン脂肪酸イソプロピル、セバチン酸ジエチル、セバチン酸ジイソプロピル、セバチン酸ジオクチル、アジピン酸ジイソプロピル、セバチン酸ジブチルオクチル、アジピン酸ジイソブチル、コハク酸ジオクチル、クエン酸トリエチル等のモノアルコールカルボン酸エステル類;乳酸セチル、リンゴ酸ジイソステアリル、モノイソステアリン酸水添ヒマシ油等のオキシ酸エステル類;トリオクタン酸グリセリル(トリ2-エチルヘキサン酸グリセリル)、トリオレイン酸グリセリル、トリイソステアリン酸グリセリル、ジイソステアリン酸グリセリル、トリ(カプリル酸/カプリン酸)グリセリル、トリ(カプリル酸/カプリン酸/ミリスチン酸/ステアリン酸)グリセリル、水添ロジントリグリセリド(水素添加エステルガム)、ロジントリグリセリド(エステルガム)、ベヘン酸エイコサン二酸グリセリル、トリオクタン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、ジオクタン酸ネオペンチルグリコール、ジカプリン酸ネオペンチルグリコール、ジオクタン酸2-ブチル-2-エチル-1,3-プロパンジオール、ジオレイン酸プロピレングリコール、テトラオクタン酸ペンタエリスリチル、水素添加ロジンペンタエリスリチル、トリエチルヘキサン酸ジトリメチロールプロパン、(イソステアリン酸/セバシン酸)ジトリメチロールプロパン、トリエチルヘキサン酸ペンタエリスリチル、(ヒドロキシステアリン酸/ステアリン酸/ロジン酸)ジペンタエリスリチル、ジイソステアリン酸ジグリセリル、テトライソステアリン酸ポリグリセリル、ノナイソステアリン酸ポリグリセリル-10、デカ(エルカ酸/イソステアリン酸/リシノレイン酸)ポリグリセリル-8、(ヘキシルデカン酸/セバシン酸)ジグリセリルオリゴエステル、ジステアリン酸グリコール(ジステアリン酸エチレングリコール)、ジネオペンタン酸3-メチル-1,5-ペンタンジオール、ジネオペンタン酸2,4-ジエチル-1,5-ペンタンジオール等の多価アルコール脂肪酸エステル類;ダイマージリノール酸ジイソプロピル、ダイマージリノール酸ジイソステアリル、ダイマージリノール酸ジ(イソステアリル/フィトステリル)、ダイマージリノール酸(フィトステリル/ベヘニル)、ダイマージリノール酸(フィトステリル/イソステアリル/セチル/ステアリル/ベヘニル)、ダイマージリノール酸ダイマージリノレイル、ジイソステアリン酸ダイマージリノレイル、ダイマージリノレイル水添ロジン縮合物、ダイマージリノール酸硬化ヒマシ油、ヒドロキシアルキルダイマージリノレイルエーテル等のダイマー酸若しくはダイマージオールの誘導体;ヤシ油脂肪酸モノエタノールアミド(コカミドMEA)、ヤシ油脂肪酸ジエタノールアミド(コカミドDEA)、ラウリン酸モノエタノールアミド(ラウラミドMEA)、ラウリン酸ジエタノールアミド(ラウラミドDEA)、ラウリン酸モノイソプロパノールアミド(ラウラミドMIPA)、パルミチン酸モノエタノールアミド(パルタミドMEA)、パルミチン酸ジエタノールアミド(パルタミドDEA)、ヤシ油脂肪酸メチルエタノールアミド(コカミドメチルMEA)等の脂肪酸アルカノールアミド類;ジメチコン(ジメチルポリシロキサン)、高重合ジメチコン(高重合ジメチルポリシロキサン)、シクロメチコン(環状ジメチルシロキサン、デカメチルシクロペンタシロキサン(単にシクロペンタシロキサンとも))、フェニルトリメチコン、ジフェニルジメチコン、フェニルジメチコン、ステアロキシプロピルジメチルアミン、(アミノエチルアミノプロピルメチコン/ジメチコン)コポリマー、ジメチコノール、ジメチコノールクロスポリマー、シリコーン樹脂、シリコーンゴム、アミノプロピルジメチコン及びアモジメチコン等のアミノ変性シリコーン、カチオン変性シリコーン、ジメチコンコポリオール等のポリエーテル変性シリコーン、ポリグリセリン変性シリコーン、糖変性シリコーン、カルボン酸変性シリコーン、リン酸変性シリコーン、硫酸変性シリコーン、アルキル変性シリコーン、脂肪酸変性シリコーン、アルキルエーテル変性シリコーン、アミノ酸変性シリコーン、ペプチド変性シリコーン、フッ素変性シリコーン、カチオン変性及びポリエーテル変性シリコーン、アミノ変性及びポリエーテル変性シリコーン、アルキル変性及びポリエーテル変性シリコーン、ポリシロキサン・オキシアルキレン共重合体等のシリコーン類;パーフルオロデカン、パーフルオロオクタン、パーフルオロポリエーテル等のフッ素系油剤類が、好ましいものとして挙げられる。
本発明において、水性組成物が油性基材を含む場合、その配合量は、例えば水性組成物の総質量に対して50乃至1質量%、好ましくは、30乃至1質量%である。
なお本発明において用いられる上記油性基剤は上述の油性基剤群の少なくとも一種であり、これら油性基剤を単独で、或いは二種以上を組み合わせて用いることができる。
本発明の皮膚外用固形基材はさらに有機酸を含んでいてもよい。また本発明の水性組成物においても有機酸を含み得る。
上記有機酸としては、アスコルビン酸、クエン酸、乳酸、グリコール酸、コハク酸、酢酸、リンゴ酸、酒石酸、フマル酸等が挙げられる。中でも好ましくはアスコルビン酸、クエン酸、乳酸が挙げられ、特にアスコルビン酸、クエン酸が挙げられる。
本発明において、有機酸の配合量は、得られる皮膚外用固形基材の総質量に対して、例えば1乃至20質量%、好ましくは、1乃至10質量%である。
また本発明において、水性組成物が有機酸を含む場合、その配合量は、例えば水性組成物の総質量に対して1乃至20質量%、好ましくは、1乃至10質量%である。
本発明において、ポリエチレングリコールの配合量は、得られる皮膚外用固形基材の総質量に対して、例えば1乃至20質量%、好ましくは、1乃至10質量%である。
また本発明において、水性組成物がポリエチレングリコールを含む場合、その配合量は、例えば水性組成物の総質量に対して1乃至20質量%、好ましくは、1乃至10質量%である。
本発明の皮膚外用固形基材又は水性組成物には、必要に応じて一般的に化粧品用添加剤及び医薬部外品用添加剤として使用可能な添加剤を配合することができる。化粧品又は医薬部外品等の皮膚外用剤に配合される生理活性物質及び機能性物質等の添加成分としては、例えば保湿剤、感触向上剤、上記以外の界面活性剤、高分子、増粘・ゲル化剤、溶剤、噴射剤、酸化防止剤、還元剤、酸化剤、防腐剤、抗菌剤、殺菌剤、キレート剤、pH調整剤、酸、アルカリ、粉体、無機塩、紫外線吸収剤、美白剤、ビタミン類及びその誘導体類、育毛用薬剤、血行促進剤、刺激剤、ホルモン類、抗しわ剤、抗老化剤、ひきしめ剤、冷感剤、温感剤、創傷治癒促進剤、刺激緩和剤、鎮痛剤、細胞賦活剤、植物・動物・微生物エキス、鎮痒剤、角質剥離・溶解剤、制汗剤、清涼剤、収れん剤、酵素、核酸、香料、色素、着色剤、染料、顔料、消炎剤、抗炎症剤、抗喘息、抗慢性閉塞性肺疾患、抗アレルギー、免疫調整剤、抗感染症剤及び抗真菌剤等が挙げられる。
ラウリルベタイン(ラウリルジメチルアミノ酢酸ベタイン)等のN-アルキル-N,N-ジメチルアミノ酸ベタイン;コカミドプロピルベタイン、ラウラミドプロピルベタイン等の脂肪酸アミドアルキル-N,N-ジメチルアミノ酸ベタイン;ココアンホ酢酸ナトリウム、ラウロアンホ酢酸ナトリウム等のイミダゾリン型ベタイン;アルキルジメチルタウリン等のアルキルスルホベタイン;アルキルジメチルアミノエタノール硫酸エステル等の硫酸型ベタイン;アルキルジメチルアミノエタノールリン酸エステル等のリン酸型ベタイン;ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルセリン、スフィンゴミエリン等のスフィンゴリン脂質、リゾレシチン、水素添加大豆リン脂質、部分水素添加大豆リン脂質、水素添加卵黄リン脂質、部分水素添加卵黄リン脂質、水酸化レシチン等のリン脂質類;シリコーン系両性界面活性剤等;高分子界面活性剤としては、ポリビニルアルコール、アルギン酸ナトリウム、デンプン誘導体、トラガントガム、アクリル酸・メタアクリル酸アルキル共重合体;シリコーン系各種界面活性剤が好ましいものとして挙げられる。
本発明の皮膚外用固形基材は、前記式(1)乃至式(3)で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなる脂質ペプチド化合物と界面活性剤及び水、更に所望により1,2-アルカンジオール又はグリセリン、脂肪酸、油性基材、有機酸及びその他添加剤とを用いて、加熱しながら混合、撹拌した後、静置放冷することによって製造され得る。またこの製造工程において、後述するように本発明の水性組成物が製造され得る。
a)上記脂質ペプチド化合物と、界面活性剤と、水を配合し、加熱して溶解液又は分散液を調製する工程
b)上記溶解液又は分散液を水に添加し、室温以上100℃未満の温度で加熱する工程
c)前記加熱工程における温度よりも低い温度になるまで撹拌しながら冷却し、その後静置放冷し、ゲル状の固形物(皮膚外用固形基材)を形成する工程
なお、1,2-アルカンジオール又はグリセリン、脂肪酸、油性基材、有機酸、ポリエチレングリコール及びその他添加剤は、a)工程において溶解液又は分散液の調製工程において添加してもよいし、b)工程において溶解液又は分散液を添加する水に予め添加していてもよい。
また得られた皮膚外用固形基材の総質量に対して、水は60質量%以上95質量%未満であることが好ましい。
また得られた溶解液又は分散液の総質量に対して、水は50質量%以上80質量%未満であることが好ましい。
a)、b)工程につづいて、液温がb)工程における温度よりも低い温度になるまで撹拌しながら冷却を行う(c)工程)。ここで冷却温度は例えば室温ないし80℃、室温ないし60℃、或いは室温ないし40℃程度である。
本発明の水性組成物を用いた皮膚外用固形基材の製造方法を以下に述べる。
水性組成物は以下に詳述するように、前述の[皮膚外用固形基材の製造方法(1)]のa)工程を経て製造される。
水性組成物を製造するには、まず、前記式(1)乃至式(3)で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなる脂質ペプチド化合物と、界面活性剤と、水を混合し、加熱して溶解液又は分散液を調製する。上記溶解液又は分散液の調製中に、所望により1,2-アルカンジオール又はグリセリン、及び/又は脂肪酸を添加してもよく、また油性基材、有機酸、ポリエチレングリコール及びその他添加剤を添加することもできる。
そして、この溶解液又は分散液を冷却することにより、水性組成物を得ることができる。
得られた溶解液又は分散液は、好ましくは前記加熱温度より低い温度、例えば室温ないし80℃、室温ないし60℃、或いは室温ないし40℃程度になるまで撹拌しながら冷却し、その後撹拌を停止して、静置することがより好ましい。
また得られた水性組成物の総質量に対して、水は50質量%以上80質量%未満であることが好ましい。
こうして得られた水性組成物は、皮膚外用固形基材の調製のためのプレミックスとして有用であり、後述するように該組成物に水やその他有効成分等を配合することにより、皮膚外用固形基材を容易に調製することが可能である。
こうして得られた本発明の水性組成物を用いて、例えば下記の工程1)~3)により、皮膚外用固形基材を製造できる。
1)水性組成物を室温以上100℃未満の温度で加熱する工程、
2)室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、及び
3)得られた混合物を冷却し、ゲルを形成させる工程。
上記水相は水を含み、さらに油性基材を含み得、また1,2-アルカンジオール又はグリセリン、脂肪酸、有機酸、ポリエチレングリコール及びその他添加剤を含んでいてもよい。
4)水性組成物を室温以上100℃未満の温度で加熱する工程、
5)室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、
6)得られた混合物を冷却し、ゲルを形成させる工程、及び
7)前記冷却過程の中途において、前記混合物に水と有機酸の混合液を添加し、さらに混合する工程。
上記水相は水を含み、さらに油性基材を含み得、また1,2-アルカンジオール又はグリセリン、脂肪酸、ポリエチレングリコール及びその他添加剤を含んでいてもよい。
前記2)工程並びに5)工程における、水相の加熱温度は好ましくは50℃乃至90℃、より好ましくは60℃乃至90℃、例えば70℃、或いは80℃である。水相の加熱は、特に油性基材などその他成分を含む場合には撹拌しながら行うことが好ましい。また水相に油性基材、さらには1,2-アルカンジオール又はグリセリン、脂肪酸、ポリエチレングリコールやその他添加剤を含んでいる場合、それらが均一に溶解・分散するまで、通常5分から50分程度、加熱(撹拌)を実施することが好ましい。なお、水相の加熱温度は、上記水性組成物の加熱温度と同じ温度としてもよい。
本工程において、添加する水と有機酸の混合溶液は、好ましくは添加する混合物と同程度の温度とすることにより、均一な混合を達成できるため好ましい。また該混合溶液には、所望により、1,2-アルカンジオール又はグリセリン、油性基材、脂肪酸、ポリエチレングリコールやその他添加剤を含んでいてもよく、それらが均一に溶解・分散するまで適当な温度にて加熱(撹拌)を実施してもよい。
例えば、前記6)工程において撹拌しながら混合物の液温が60℃程度となったとき、液温を60℃程度とした水と有機酸の混合溶液を混合物に添加し、さらに混合して系を均一とし、その後、好ましくは撹拌を停止し、静置して冷却することにより、ゲル(皮膚外用固形基材)を得ることができる。
本実施例においてゲル化剤として用いた脂質ペプチドを以下に示す方法で合成した。
500mLの4つ口フラスコに、ヒスチジン14.2g(91.6mmol)、N-パルミトイル-Gly-メチル30.0g(91.6mmol)、トルエン300gを投入し、塩基であるナトリウムメトキサイド 28%メタノール溶液35.3g(183.2mmol)を加え、油浴で60℃に加熱し1時間撹拌を続けた。その後、油浴を外し、25℃まで放冷し、この溶液をアセトン600gで再沈殿させ、ろ取した。ここで得られた固体を、水600gとメタノール750gの混合溶液に溶解し、ここに6規定塩酸30.5ml(183.2mmol)を加えて中和し固体を析出させ、ろ過した。次に、得られた固体をテトラヒドロフラン120gと水30gの混合液に60℃で溶解させ、酢酸エチル150gを加え、60℃から30℃まで冷却した。その後、析出した固体をろ過した。さらに得られた固体を、テトラヒドロフラン120gとアセトニトリル60g溶剤中に溶解し、60℃に加熱し、1時間撹拌した後に冷却し、ろ過した。ここで得られた固体を水120gで洗浄し、ろ過後に減圧乾燥を行いN-パルミトイル-Gly-Hisフリー体(以下、単にPal-GHとも称する)の白色の結晶、26.9g(収率65%)を得た。
(皮膚外用固形基材の調製方法)
下記表1に従って、A相の各成分をサンプル管No.5に秤量した。秤量したA相を70℃以上に加熱し、均一に溶解させた。一方、別のサンプル管No.5にB相である水5.0gを秤量し、70℃以上に加熱した。その後、A相をB相に添加し、加熱した状態で混合し約30秒程度撹拌した後、静置放冷を行った。
YAMADEN RHEONER II CREEP METER RE2-33005B((株)山電)にて、測定速度:0.5mm/秒、測定歪率:20%、格納ピッチ:0.10秒、治具:30349-3を用いて破断強度測定を行った。
得られた結果を表1に示す。
(皮膚外用固形基材の調製方法)
下記表2に従って、A相の各成分をサンプル管No.5に秤量した。秤量したA相を70℃以上に加熱し、均一に溶解させた。一方、別のサンプル管No.5にB相の各成分を秤量し、70℃以上に加熱した。その後、A相をB相に添加し、加熱した状態で混合し約30秒程度撹拌した後、60℃になるまで撹拌冷却を行った。60℃以降は、静置放冷を行った。
上記(破断強度測定方法)と同様に破断強度測定を行った。
得られた結果を表2に示す。
一方、1,2-アルカンジオール及び界面活性剤を含まない比較例1及び界面活性剤を含まない比較例2は、破断応力が検出できず、スティック状の基材としては強度が足りないという結果となった。
下記表3に従って、A相の各成分をサンプル管No.5に秤量した。秤量したA相を70℃以上に加熱し、均一に溶解させた。一方、別のサンプル管No.5にB相の各成分を秤量し、70℃以上に加熱した。その後、A相をB相に添加し、加熱した状態で混合し約30秒程度撹拌した後、60℃になるまで撹拌冷却を行った。60℃以降は、静置放冷を行った。なお実施例14のB相におけるグリセリンは、保湿剤・感度向上剤として添加したものである。
上記(破断強度測定方法)と同様に破断強度測定を行った。
得られた結果を表3に示す。
下記表4に従って、A相の各成分をマルエムサンプル管No.3に秤量した。秤量したA相を水浴(設定温度85℃)にて加熱し、均一に溶解させた。一方、スターラーチップを入れた別のマルエムサンプル管No.5にB相の各成分を秤量し、これを水浴(設定温度85℃)で加熱した。A相をB相に添加し、液温が60℃程度となるまで撹拌冷却を開始した。一方、別のサンプル管No.5にC相の各成分を秤量し、液温が60℃程度となるように加熱した。A+B相の液温が60℃になったところで、液温が60℃程度となったC相を添加し、約30秒程度撹拌した後、静置放冷した。
上記(破断強度測定方法)と同様に破断強度測定を行った。
得られた結果を表4に示す。
下記表5に従って、A相の各成分をマルエムサンプル管No.7に秤量した。秤量したA相を水浴(設定温度80℃)にて液温が80℃になるまで加熱・撹拌し、均一に溶解させた。なおこのとき撹拌にはマグネチックスターラーを用いた。一方、スターラーチップを入れた別のマルエムサンプル管No.7にB相の各成分を秤量し、これを水浴(設定温度80℃)にて液温が80℃となるまで加熱・撹拌した。A相をB相に添加し、上記設定温度にて加熱・撹拌を1分間継続した。A相+B相が入ったサンプル管を水浴から外して、冷却を開始した。冷却開始と同時にマグネチックスターラーを除去し、その後の撹拌はスパチュラを用いて液温が60℃になるまで手動にて行った。
液温が60℃となったところで、金属製の容器(内径φ9.5mm、(株)ヒダン製の口紅容器、容器本体と本体全体を覆うように蓋が取り付けられて成る)を準備し、容器本体にすりきり一杯になるまで混合物を充填し、その後すぐに容器本体の開口部に、充填した混合物を密封するようにアルミテープを貼り、さらにその上から容器本体を覆うように仮蓋としてカプセルをかぶせ、充填密封試料を作製した。こうした充填密封試料を各例毎に4本作製し(N-1~N-4)、その後室温にて30分間、静置放冷を行った。
静置30分後に仮蓋であるカプセル除去を行い、蓋を付けた。
金属容器に蓋をしたのち質量を計測し、事前に測定しておいた金属容器(容器本体、蓋、アルミテープ)の質量を差し引いて、充填した試料の質量を算出した(調製時の試料の質量)。その後、蓋をした充填密封試料を45℃設定恒温槽内に2週間保管し、再度質量を測定して、2週間保管後の充填試料の質量を算出した(保管後の試料の質量)。2週間保管後の質量損失率を下記式にて算出した。得られた結果を表5に示す。質量損失率は低い数値であるほど試料の質量損失が少なく、すなわち、試料の経時安定性が高いことを示す。
質量損失率(%)=100-{[保管後の質量/調製時の材料の質量]×100}
下記表6に従って、A相の各成分をサンプル管No.5に秤量した。秤量したA相を70℃以上に加熱し、均一に溶解させた。一方、別のサンプル管No.5にB相である水5.0gを秤量し、70℃以上に加熱した。その後、A相をB相に添加し、加熱した状態で混合し約30秒程度撹拌した後、静置放冷を行った。
上記(破断強度測定方法)と同様に破断強度測定を行った。
得られた結果を表6に示す。
Claims (21)
- 界面活性剤及び水と、下記式(1)乃至式(3)で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなる脂質ペプチド型化合物とを含む、皮膚外用固形基材。
- 1,2-アルカンジオール又はグリセリンを更に含む、請求項1に記載の皮膚外用固形基材。
- 少なくとも一種の脂肪酸を更に含む、請求項1又は請求項2に記載の皮膚外用固形基材。
- 少なくとも一種の油性基剤を更に含む、請求項1乃至請求項3のうち何れか一項に記載の皮膚外用固形基材。
- 少なくとも一種の有機酸を更に含む、請求項1乃至請求項4のうち何れか一項に記載の皮膚外用固形基材。
- 前記界面活性剤が、エチレングリコールアルキルエーテル、リン脂質、ポリグリセリン脂肪酸エステル及びポリオキシエチレンポリオキシプロピレンアルキルエーテルからなる群から選択される1種類以上の化合物である、請求項1乃至請求項5のうち何れか一項に記載の皮膚外用固形基材。
- 前記脂肪酸がステアリン酸である、請求項3乃至請求項6のうち何れか一項に記載の皮膚外用固形基材。
- 前記有機酸がアスコルビン酸である、請求項5乃至請求項7のうち何れか一項に記載の皮膚外用固形基材。
- ポリエチレングリコールを更に含有する、請求項1乃至請求項8のうち何れか一項に記載の皮膚外用固形基材。
- 化粧品又は医薬用である、請求項1乃至請求項9のうち何れか一項に記載の皮膚外用固形基材。
- スティック状である、請求項1乃至請求項10のうち何れか一項に記載の皮膚外用固形材。
- 界面活性剤及び水と、下記式(1)乃至式(3)で表される化合物又はその薬学的に使用可能な塩のうちの少なくとも一種からなる脂質ペプチド型化合物とを含む、水性組成物。
- 1,2-アルカンジオール又はグリセリンを更に含む、請求項12に記載の水性組成物。
- 少なくとも一種の脂肪酸を更に含む、請求項12又は請求項13に記載の水性組成物。
- 前記界面活性剤が、エチレングリコールアルキルエーテル、リン脂質、ポリグリセリン脂肪酸エステル及びポリオキシエチレンポリオキシプロピレンアルキルエーテルからなる群から選択される1種類以上の化合物である、請求項12乃至請求項14のうち何れか一項に記載の水性組成物。
- 皮膚外用固形基材の調製のためのプレミックスである、請求項12乃至請求項15のうち何れか一項に記載の水性組成物。
- 請求項12乃至請求項16のうち何れか一項に記載の水性組成物を室温以上100℃未満の温度で加熱する工程、
室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、及び
得られた混合物を冷却し、ゲルを形成させる工程、
を含む請求項1に記載の皮膚外用固形基材の製造方法。 - 前記水相が少なくとも一種の油性基材を含む、請求項17に記載の製造方法。
- 前記水相がポリエチレングリコールを含む、請求項17に記載の製造方法。
- 請求項12乃至請求項16のうち何れか一項に記載の水性組成物を室温以上100℃未満の温度で加熱する工程、
室温以上100℃未満の温度で加熱した水相に、上記加熱した水性組成物を添加し、混合する工程、
得られた混合物を冷却し、ゲルを形成させる工程、及び
前記冷却過程の中途において、前記混合物に水と有機酸の混合液を添加し、さらに混合する工程、
を含む請求項5に記載の皮膚外用固形基材の製造方法。 - 前記水相が少なくとも一種の油性基材を含む、請求項20に記載の製造方法。
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2014
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- 2014-12-25 BR BR112016014595-0A patent/BR112016014595B1/pt not_active IP Right Cessation
- 2014-12-25 EP EP21169841.0A patent/EP3881823B1/en active Active
- 2014-12-25 US US15/107,960 patent/US10092496B2/en active Active
- 2014-12-25 TW TW107142102A patent/TW201907903A/zh unknown
- 2014-12-25 TW TW103145896A patent/TWI650140B/zh active
- 2014-12-25 KR KR1020227002428A patent/KR20220016301A/ko not_active IP Right Cessation
- 2014-12-25 KR KR1020237038115A patent/KR102674582B1/ko active IP Right Grant
- 2014-12-25 CN CN201480070175.8A patent/CN105848631A/zh active Pending
- 2014-12-25 EP EP14873681.2A patent/EP3087971B1/en active Active
- 2014-12-25 CN CN202110187486.4A patent/CN112891245A/zh active Pending
- 2014-12-25 ES ES14873681T patent/ES2745290T3/es active Active
- 2014-12-25 EP EP19169794.5A patent/EP3533439A1/en not_active Withdrawn
- 2014-12-25 KR KR1020167013775A patent/KR20160100931A/ko not_active IP Right Cessation
- 2014-12-25 JP JP2015555015A patent/JP6624380B2/ja active Active
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Cited By (7)
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WO2016208473A1 (ja) * | 2015-06-24 | 2016-12-29 | 日産化学工業株式会社 | 脂質ペプチド型化合物を含有するスティック状基材 |
WO2016208460A1 (ja) * | 2015-06-24 | 2016-12-29 | 日産化学工業株式会社 | 脂質ペプチド型化合物を含有するスティック状基材の硬度調整方法 |
WO2016208442A1 (ja) * | 2015-06-24 | 2016-12-29 | 日産化学工業株式会社 | 脂質ペプチド型化合物を含むスティック状基材 |
US10639263B2 (en) | 2015-06-24 | 2020-05-05 | Nissan Chemical Industries, Ltd. | Method for adjusting hardness of stick-shaped base material comprising lipid peptide compound |
WO2018190383A1 (ja) * | 2017-04-12 | 2018-10-18 | 日産化学株式会社 | 顔料又は粉体用分散剤を含有する分散液 |
JP2022114423A (ja) * | 2021-01-26 | 2022-08-05 | 広東丸美生物技術股▲フン▼有限公司 | 化粧品濃縮乳化マトリックス及びその調製方法と使用 |
JP7153778B2 (ja) | 2021-01-26 | 2022-10-14 | 広東丸美生物技術股▲フン▼有限公司 | 化粧品濃縮乳化マトリックス及びその調製方法と使用 |
Also Published As
Publication number | Publication date |
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TW201536340A (zh) | 2015-10-01 |
TWI650140B (zh) | 2019-02-11 |
ES2745290T3 (es) | 2020-02-28 |
US20160324749A1 (en) | 2016-11-10 |
JP6624380B2 (ja) | 2019-12-25 |
EP3533439A1 (en) | 2019-09-04 |
US10092496B2 (en) | 2018-10-09 |
EP3881823A1 (en) | 2021-09-22 |
EP3881823B1 (en) | 2023-01-25 |
CN112891245A (zh) | 2021-06-04 |
BR112016014595B1 (pt) | 2021-05-18 |
CN105848631A (zh) | 2016-08-10 |
BR112016014595A8 (pt) | 2018-04-17 |
HK1225619A1 (zh) | 2017-09-15 |
EP3087971A4 (en) | 2017-08-30 |
KR102674582B1 (ko) | 2024-06-13 |
EP3087971B1 (en) | 2019-06-12 |
KR20160100931A (ko) | 2016-08-24 |
EP3087971A1 (en) | 2016-11-02 |
KR20220016301A (ko) | 2022-02-08 |
KR20230155620A (ko) | 2023-11-10 |
TW201907903A (zh) | 2019-03-01 |
JPWO2015099074A1 (ja) | 2017-03-23 |
BR112016014595A2 (pt) | 2017-08-08 |
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