WO2015174500A1 - 脂質ペプチド型化合物を含有する増粘性組成物 - Google Patents
脂質ペプチド型化合物を含有する増粘性組成物 Download PDFInfo
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- WO2015174500A1 WO2015174500A1 PCT/JP2015/063933 JP2015063933W WO2015174500A1 WO 2015174500 A1 WO2015174500 A1 WO 2015174500A1 JP 2015063933 W JP2015063933 W JP 2015063933W WO 2015174500 A1 WO2015174500 A1 WO 2015174500A1
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- 0 *C(C(NC(*)C(NC(*=*)C(NC(*)C(O)=O)=O)=O)=O)NC(*)=O Chemical compound *C(C(NC(*)C(NC(*=*)C(NC(*)C(O)=O)=O)=O)=O)NC(*)=O 0.000 description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/16—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
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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
- A61K8/33—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- 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
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K2800/10—General cosmetic use
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/48—Thickener, Thickening system
Definitions
- the present invention relates to a thickening composition containing a lipid peptide-type compound, particularly to a thickening composition for external use on the skin.
- salts may be blended as a moisturizing agent, a depigmenting agent, an amino acid, or a vitamin in a composition for external use on skin for medical materials or cosmetics. Therefore, for use in the field of cosmetics, it is necessary to develop a thickening composition having salt resistance that does not lose its viscosity even in the presence of these salts.
- salt resistance is imparted by crosslinking hyaluronic acid, which is a polymer.
- crosslinking hyaluronic acid
- the present invention has been made based on the above circumstances, and the problem to be solved is to provide a thickening composition that does not lose its viscosity even in the presence of organic acids such as ascorbic acid and salts thereof. is there.
- the present invention provides, as a first aspect, from at least one of a polyhydric alcohol, water, an organic acid, a compound represented by the following formulas (1) to (3), or a pharmaceutically usable salt thereof. It is related with the thickening composition containing the lipid peptide type compound which becomes.
- 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 thickening composition according to the second aspect, wherein the fatty acid is stearic acid.
- the present invention relates to the thickening composition according to the third aspect, wherein the surfactant is one or more compounds selected from the group consisting of ethylene glycol alkyl ethers.
- the present invention relates to the thickening composition according to any one of the first to fifth aspects, wherein the organic acid is ascorbic acid.
- a seventh aspect including a polyhydric alcohol, water, and a lipid peptide type compound comprising at least one of a compound represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof, It is related with the raw material premix in the case of manufacture of the thickening composition of any one of a 1st viewpoint thru
- 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 can provide a composition capable of thickening even in the presence of a high concentration of organic acids and salts thereof that cannot be thickened by conventional thickeners.
- the lipid peptide compound contained in the thickening composition of the present invention is a very safe artificial low molecular weight compound composed only of a lipid and a peptide.
- various components contained as additives in the thickening composition of the present invention are general-purpose additives as additives for foods, cosmetics, and pharmaceuticals. That is, the thickening composition of the present invention has high biological safety, and is particularly useful in the above applications from the viewpoint of high safety required for medical materials or cosmetic materials.
- the present invention relates to a lipid peptide type compound comprising a polyhydric alcohol, water and an organic acid, and at least one of compounds represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof: And a thickening composition containing a fatty acid, a surfactant and other additives as required.
- a thickening composition containing a fatty acid, a surfactant and other additives as required.
- the lipid peptide type compound used in the thickening composition of the present invention is a compound (lipid peptide) represented by the following formulas (1) to (3) or a pharmaceutically usable salt thereof (hydrophobic site).
- a low molecular compound having a lipid 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 the adjacent carbonyl group include lauroyl group, dodecylcarbonyl group, myristoyl group, tetradecylcarbonyl group, palmitoyl group, margaroyl group, oleoyl group, and elideoyl group Linoleoyl group, stearoyl group, baccenoyl group, octadecylcarbonyl group, arachidyl group, eicosylcarbonyl group, behenoyl group, ercanoyl group, docosylcarbonyl group, lignoceyl group, nerbonoyl group, etc. Examples include lauroyl group
- 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 that may have 1 to 3 nitrogen atoms.
- it represents a 6-membered ring group or a condensed heterocyclic group composed of a 5-membered ring and a 6-membered ring.
- 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—X group is preferably an aminomethyl group, 2-aminoethyl group, 3-aminopropyl group, 4-aminobutyl group, carbamoylmethyl group, 2-carbamoylethyl group, 3- It represents a carbamoylbutyl group, 2-guanidinoethyl group, 3-guanidinobutyl group, pyrrolemethyl group, 4-imidazolemethyl group, pyrazolemethyl group, or 3-indolemethyl group, more preferably 4-aminobutyl group, carbamoylmethyl.
- Particularly preferred lipid peptide in the compound represented by the above formula (1) as the 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 ) n—X group, and preferably at least one of R 5 to R 7 represents a — (CH 2 ) n—X group.
- n a number from 1 to 4
- X represents an amino group, a guanidino group, a —CONH 2 group, or a 5-membered or 6-membered ring group that may have 1 to 3 nitrogen atoms, or a 5-membered ring and a 6-membered ring group.
- a condensed heterocyclic group composed of a member ring is represented.
- preferred specific examples of 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 ) n—X group, and preferably at least one of R 9 to R 12 represents a — (CH 2 ) n—X group.
- n a number from 1 to 4
- X represents an amino group, a guanidino group, a —CONH 2 group, or a 5-membered or 6-membered ring group that may have 1 to 3 nitrogen atoms, or a 5-membered ring and a 6-membered ring group.
- a condensed heterocyclic group composed of a member ring is represented.
- preferred specific examples of 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 preferably 0.1 to 10% by mass, more preferably 0.1 to 5% by mass, and still more preferably based on the total mass of the resulting thickening composition. 0.25 to 1% by mass.
- the lipid peptide type compound used in the present invention comprises at least one of the compounds (lipid peptides) represented by the above formulas (1) to (3) or a pharmaceutically usable salt thereof. Can be used alone or in combination of two or more.
- the polyhydric alcohol used in the thickening composition of the present invention is a compound having two or more hydroxyl groups in the molecule, and these polyhydric alcohols can be used alone or in combination of two or more.
- examples of the polyhydric alcohol include glycerin, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol and 1,2-decanediol, 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 Examples include glycol and polypropylene glycol.
- Preferred are 1,2-pentanediol, 1,2-hexanediol, and 1,2-octanediol. More preferred is 1,2-pentanediol or 1,2-hexanediol.
- the blending amount of the polyhydric alcohol used is, for example, 0.1 to 95% by weight, preferably 0.1 to 80% by weight, more preferably, based on the total weight of the resulting thickening composition. 0.1 to 50% by mass.
- Organic acid examples include ascorbic acid, citric acid, lactic acid, glycolic acid, succinic acid, acetic acid, malic acid, tartaric acid, fumaric acid, phosphoric acid, hydrochloric acid, and sulfuric acid.
- ascorbic acid, citric acid, and lactic acid are used. More preferably, ascorbic acid and citric acid are used.
- the amount of the organic acid used is, for example, 0.01 to 20% by mass, preferably 0.01 to 15% by mass, and more preferably 0% with respect to the total mass of the thickening composition obtained. .1 to 10% by mass.
- the thickening 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.
- 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 preferred are capric acid, lauric acid, myristic acid, palmitic acid and stearic acid.
- the amount of fatty acid used is preferably 0.01 to 1% by mass, more preferably 0.01 to 0.5% by mass, and more preferably, based on the total mass of the resulting thickening composition. Preferably it is 0.025 to 0.1 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.
- a compound having a hydrophilic part and a hydrophobic part in the molecule and having a betaine structure in the hydrophilic part hereinafter also referred to as a betaine compound
- ethylene Glycol alkyl ether a compound having a hydrophilic part and a hydrophobic part in the molecule and having a betaine structure in the hydrophilic part
- ethylene Glycol alkyl ether a compound having a hydrophilic part and a hydrophobic part in the molecule and having a betaine structure in the hydrophilic part
- ethylene Glycol alkyl ether ethylene Glycol alkyl ether
- 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 lauryl ether, polyoxyethylene palmitoyl ether, polyoxyethylene stearyl ether and the like. Polyoxyethylene lauryl ether and polyoxyethylene stearyl ether are preferable.
- the blending amount of the surfactant is preferably 0.1 to 10% by mass, more preferably 0.1 to 5% by mass, and still more preferably 0, with respect to the total mass of the resulting thickening composition. .25 to 1% by 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 additive component such as a physiologically active substance and a functional substance to be blended in an external preparation for skin such as cosmetics or quasi-drugs include, for example, a moisturizer / feel improver; a surfactant other than the above; Gelling agents; Solvents, propellants; Antioxidants; Reducing agents; Oxidizing agents; Preservatives / antibacterial agents / bactericides; Chelating agents; pH adjusters / acids / alkalis; Powders; Inorganic salts; Whitening agents; vitamins and derivatives thereof; hair-restoring agents / blood circulation promoters / stimulants; hormones; anti-wrinkle agents, anti-aging agents, squeeze agents, cooling sensation agents, warming sensation agents, wound healing promoters, stimulation relief Agent, analgesic
- humectants and feel improvers examples include glycerin, 1,3-butylene glycol, propylene glycol, 3-methyl-1,3-butanediol, 1,3-propanediol, 2-methyl-1,3-propanediol, Polyols such as trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, ethylene glycol / propylene glycol copolymer and polymers thereof; diethylene glycol monoethyl ether (Ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol dibutyl ether, etc.
- Ethoxydiglycol ethylene glycol monoethyl ether
- ethylene glycol monobutyl ether diethylene glycol dibutyl
- Water-soluble esters such as polyglyceryl-10 and tetradecandioic acid polyglyceryl-10; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, maltitol; glucose, fructose, galactose Mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, trehalose, lactose, raffinose, gluconic acid, glucuronic acid, cyclodextrins ( ⁇ -, ⁇ -, ⁇ -cyclodextrin, and maltosylated, hydroxy Modified cyclodextrins such as alkylation), ⁇ -glucan, chitin, chitosan, heparin and its derivatives, pectin, arabinogalactan, dextrin, dextran, glyco Sugars
- 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
- Amino acid betaines include imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkylsulfobetaines such as alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; phosphate-type betaines such as alkyldimethylaminoethanol phosphate Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and other sphingophospholipids, lysolecithin, hydrogenated soybean phospholipid, partial water Phospholipids such as added soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, and hydroxylated lecithin; silicone-based amphoteric surfactants; polymer surfactants include polyvinyl alcohol, sodium alginate, starch Derivatives, tragacanth gum,
- 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 extracts and tinctures such as assembly extract, red pepper tincture, ginger tincture, ginger extract, cantalis tincture; capsaicin, nonylic acid vanillylamide, 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 and 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 thickening composition 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 polyhydric alcohol, water. And an organic acid, and if necessary, using a fatty acid, a surfactant, and other additives, mixing and stirring while heating, and then allowing to stand and allowing to cool.
- the thickening composition of the present invention is produced by the following process as an example. a) Step of preparing a solution or dispersion (premix phase) by mixing the lipid peptide compound and polyhydric alcohol and heating to prepare a solution or dispersion (premix phase). Step c) heating at a temperature of less than c) mixing polyhydric alcohol, water and organic acid and heating to prepare a solution or dispersion (aqueous phase) d) said solution or dispersion (water phase) Step e) heating at a temperature of room temperature to less than 100 ° C. e) Mixing the heated premix phase and the heated aqueous phase, cooling with stirring until the temperature is lower than the temperature in the heating step.
- Fatty acids, surfactants and other additives may be added in the preparation step of the solution or dispersion (premix phase) in step a), or the solution or dispersion (water phase) in step c). ) May be added in the preparation step.
- water is 20 mass% or more and less than 90 mass% with respect to the total mass of the obtained thickening composition.
- water is 40 to 80 mass% with respect to the total mass of the obtained solution or dispersion (aqueous phase).
- the heating temperature in the steps b) and d) 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, polyhydric alcohol, organic acid and other components used, and their blending amount, but it can usually be dissolved and dispersed in about 5 to 50 minutes. It is.
- cooling is performed with stirring until the liquid temperature is lower than that in steps b) and d) (step e)).
- the cooling temperature is, for example, room temperature to 80 ° C., room temperature to 60 ° C., or room temperature to 40 ° C.
- the present invention also includes a lipid peptide type compound comprising at least one of a compound represented by the above formulas (1) to (3) or a pharmaceutically usable salt thereof, polyhydric alcohol, water, It also relates to a raw material premix in the production of the thickening composition of the present invention.
- the premix which further contains at least 1 type of fatty acid is preferable.
- 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, filtered and dried under reduced pressure to obtain 26.9 g (yield 65%) of white crystals of N-palmitoyl-Gly-His free form.
- compositions 1 to 11 shown in Table 1 were prepared according to the following procedure.
- the components of the premix phase were weighed into sample tube No. 5 (manufactured by Maruemu) in accordance with the blending amounts shown in Table 1.
- the components of the aqueous phase were weighed in a 300 mL tall beaker according to the blending amounts shown in Table 1.
- the premix phase and the aqueous phase were heated to 70 ° C. or higher, respectively.
- the premix phase and the aqueous phase were mixed and then allowed to cool with stirring.
- compositions 12 to 21 shown in Table 2 were prepared by the following procedure.
- the components of the premix phase were weighed into sample tube No. 5 (manufactured by Maruemu) in accordance with the blending amounts shown in Table 2.
- the components of the aqueous phase were weighed in a 300 mL tall beaker according to the blending amounts shown in Table 2.
- the premix phase and the aqueous phase were heated to 70 ° C. or higher, respectively.
- the premix phase and the aqueous phase were mixed and then allowed to cool with stirring. Stirring was stopped when the liquid temperature reached 40 ° C., and a composition sample was prepared.
- the viscosity of the prepared sample was measured using a viscometer (AND VIBRO VISCOMETER SU-1A). As the viscosity value, a value one minute after giving vibration was used. The results are shown in Table 2.
- Pal-GH means the lipid peptide (N-palmitoyl-Gly-His free form) obtained in Synthesis Example 1, and BG means 3-butylene glycol.
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Abstract
Description
第2観点として、少なくとも一種の脂肪酸を更に含む、第1観点に記載の増粘性組成物に関する。
第3観点として、少なくとも一種の界面活性剤を更に含む、第1観点又は第2観点に記載の増粘性組成物に関する。
第4観点として、前記脂肪酸が、ステアリン酸である、第2観点に記載の増粘性組成物に関する。
第5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3観点に記載の増粘性組成物に関する。
第6観点として、前記有機酸が、アスコルビン酸である第1観点乃至第5観点のいずれか1項に記載の増粘性組成物に関する。
第7観点として、多価アルコール、水および、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を含む、第1観点乃至第6観点のいずれか1項に記載の増粘性組成物の製造の際の原料プレミックスに関する。
第8観点として、少なくとも一種の脂肪酸を更に含む第7観点に記載のプレミックスに関する。
また本発明の増粘性組成物に含まれる脂質ペプチド化合物は、脂質とペプチドのみから構成される非常に安全性の高い人工低分子化合物である。さらに本発明の増粘性組成物において添加剤として含まれる各種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、本発明の増粘性組成物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。
以下、各構成成分について説明する。
本発明の増粘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-X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、好ましくは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員環基若しくは6員環基、又は5員環と6員環から構成される縮合複素環基を表す。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、好ましくは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員環基若しくは6員環基、又は5員環と6員環から構成される縮合複素環基を表す。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。
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、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。
本発明の増粘性組成物において使用される多価アルコールとして、分子内に2個以上の水酸基を有する化合物であり、これら多価アルコールを単独で、或いは二種以上を組み合わせて用いることができる。多価アルコールとしては、例えばグリセリン、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、1,3-ブチレングリコール、プロピレングリコール、3-メチル-1,3-ブタンジオール、1,3-プロパンジオール、2-メチル-1,3-プロパンジオール、トリメチロールプロパン、ペンタエリスリトール、ヘキシレングリコール、ジグリセリン、ポリグリセリン、ジエチレングリコール、ポリエチレングリコール、ジプロピレングリコール、ポリプロピレングリコールが挙げられる。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。
本発明において、使用される多価アルコールの配合量は、得られる増粘性組成物の総質量に対して、例えば0.1乃至95質量%、好ましくは0.1乃至80質量%、より好ましくは0.1乃至50質量%である。
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、リン酸、塩酸、硫酸が挙げられる。好ましくは、アスコルビン酸、クエン酸、乳酸が挙げられる。より好ましくは、アスコルビン酸、クエン酸が挙げられる。
本発明において、使用される有機酸の配合量は、得られる増粘性組成物の総質量に対して、例えば0.01乃至20質量%、好ましくは0.01乃至15質量%、より好ましくは0.1乃至10質量%である。
本発明の増粘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る。
本発明において、使用される脂肪酸の配合量は、得られる増粘性組成物の総質量に対して、好ましくは0.01乃至1質量%、より好ましくは0.01乃至0.5質量%、さらに好ましくは0.025乃至0.1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。
本発明の増粘性組成物において使用され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)或いは、エチレングリコール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。
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(又は水性固体状組成物、溶解液又は分散液)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、噴射剤類;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;無機塩類;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;酵素類;核酸類;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;並びに抗感染症剤及び抗真菌剤等が挙げられる。
非イオン界面活性剤としては、ラウレス(ポリオキシエチレンラウリルエーテル)類、セテス(ポリオキシエチレンセチルエーテル)類、ステアレス(ポリオキシエチレンステアリルエーテル)類、ベヘネス類(ポリオキシエチレンベヘニルエーテル)、イソステアレス(ポリオキシエチレンイソステアリルエーテル)類、オクチルドデセス(ポリオキシエチレンオクチルドデシルエーテル)類等の種々のポリオキシエチレン付加数のポリオキシエチレンアルキルエーテル類;ポリオキシエチレンアルキルフェニルエーテル;ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンヒマシ油、ポリオキシエチレン硬化ヒマシ油モノイソステアレート、ポリオキシエチレン硬化ヒマシ油トリイソステアレート、ポリオキシエチレン硬化ヒマシ油モノピログルタミン酸モノイソステアリン酸ジエステル、ポリオキシエチレン硬化ヒマシ油マレイン酸等のヒマシ油及び硬化ヒマシ油誘導体;ポリオキシエチレンフィトステロール;ポリオキシエチレンコレステロール;ポリオキシエチレンコレスタノール;ポリオキシエチレンラノリン;ポリオキシエチレン還元ラノリン;ポリオキシエチレン・ポリオキシプロピレンセチルエーテル、ポリオキシエチレン・ポリオキシプロピレン2-デシルテトラデシルエーテル、ポリオキシエチレン・ポリオキシプロピレンモノブチルエーテル、ポリオキシエチレン・ポリオキシプロピレン水添ラノリン、ポリオキシエチレン・ポリオキシプロピレングリセリンエーテル等の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;ポリオキシエチレン・ポリオキシプロピレングリコール;PPG-9ジグリセリル等の(ポリ)グリセリンポリオキシプロピレングリコール;ステアリン酸グリセリル、イソステアリン酸グリセリル、パルミチン酸グリセリル、ミリスチン酸グリセリル、オレイン酸グリセリル、ヤシ油脂肪酸グリセリル、モノ綿実油脂肪酸グリセリン、モノエルカ酸グリセリン、セスキオレイン酸グリセリン、α,α’-オレイン酸ピログルタミン酸グリセリン、モノステアリン酸グリセリンリンゴ酸等のグリセリン脂肪酸部分エステル類;ステアリン酸ポリグリセリル-2、同3、同4、同5、同6、同8、同10、ジステアリン酸ポリグリセリル-6、同10、トリステアリン酸ポリグリセリル-2、デカステアリン酸ポリグリセリル-10、イソステアリン酸ポリグリセリル-2、同3、同4、同5、同6、同8、同10、ジイソステアリン酸ポリグリセリル-2(ジイソステアリン酸ジグリセリル)、同3、同10、トリイソステアリン酸ポリグリセリル-2、テトライソステアリン酸ポリグリセリル-2、デカイソステアリン酸ポリグリセリル-10、オレイン酸ポリグリセリル-2、同3、同4、同5、同6、同8、同10、ジオレイン酸ポリグリセリル-6、トリオレイン酸ポリグリセリル-2、デカオレイン酸ポリグリセリル-10等のポリグリセリン脂肪酸エステル;モノステアリン酸エチレングリコール等のエチレングリコールモノ脂肪酸エステル;モノステアリン酸プロピレングリコール等のプロピレングリコールモノ脂肪酸エステル;ペンタエリスリトール部分脂肪酸エステル;ソルビトール部分脂肪酸エステル;マルチトール部分脂肪酸エステル;マルチトールエーテル;ソルビタンモノオレエート、ソルビタンモノイソステアレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタントリオレエート、ペンタ-2-エチルヘキシル酸ジグリセロールソルビタン、テトラ-2-エチルヘキシル酸ジグリセロールソルビタン等のソルビタン脂肪酸エステル;ショ糖脂肪酸エステル、メチルグルコシド脂肪酸エステル、ウンデシレン酸トレハロース等の糖誘導体部分エステル;カプリリルグルコシド等のアルキルグルコシド;アルキルポリグリコシド;ラノリンアルコール;還元ラノリン;ポリオキシエチレンジステアレート、ポリチレングリコールジイソステアレート、ポリオキシエチレンモノオレエート、ポリオキシエチレンジオレエート等のポリオキシエチレン脂肪酸モノ及びジエステル;ポリオキシエチレン・プロピレングリコール脂肪酸エステル;ポリオキシエチレングリセリンモノステアレート、ポリオキシエチレングリセリンモノイソステアレート、ポリオキシエチレングリセリントリイソステアレート等のポリオキシエチレンモノオレエート等のポリオキシエチレングリセリン脂肪酸エステル;ポリオキシエチレンソルビタンモノオレエート、ポリオキシエチレンソルビタンモノステアレート、ポリオキシエチレンソルビタンモノオレート、ポリオキシエチレンソルビタンテトラオレエート等のポリオキシエチレンソルビタン脂肪酸エステル;ポリオキシエチレンソルビトールモノラウレート、ポリオキシエチレンソルビトールモノオレエート、ポリオキシエチレンソルビトールペンタオレエート、ポリオキシエチレンソルビトールモノステアレート等のポリオキシエチレンソルビトール脂肪酸エステル;ポリオキシエチレンメチルグルコシド脂肪酸エステル;ポリオキシエチレンアルキルエーテル脂肪酸エステル;ポリオキシエチレンソルビトールミツロウ等のポリオキシエチレン動植物油脂類;イソステアリルグリセリルエーテル、キミルアルコール、セラキルアルコール、バチルアルコール等のアルキルグリセリルエーテル類;多価アルコールアルキルエーテル;ポリオキシエチレンアルキルアミン;テトラポリオキシエチレン・テトラポリオキシプロピレン-エチレンジアミン縮合物類;サポニン、ソホロリピッド等の天然系界面活性剤;ポリオキシエチレン脂肪酸アミド;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;ラウラミンオキシド、コカミンオキシド、ステアラミンオキシド、ベヘナミンオキシド等のアルキルジメチルアミンオキシド;アルキルエトキシジメチルアミンオキシド;ポリオキシエチレンアルキルメルカプタン;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、ポリシロキサン・オキシアルキレン共重合体、ポリグリセリン変性シリコーン、糖変性シリコーン等のシリコーン系非イオン性界面活性剤等;
陽イオン性界面活性剤としては、ベヘントリモニウムクロリド、ステアルトリモニウムクロリド、セトリモニウムクロリド、ラウリルトリモニウムクロリド等のアルキルトリメチルアンモニウムクロリド;ステアリルトリモニウムブロミド等のアルキルトリメチルアンモニウムブロミド;ジステアリルジモニウムクロリド、ジココジモニウムクロリド等のジアルキルジメチルアンモニウムクロリド;ステアラミドプロピルジメチルアミン、ステアラミドエチルジエチルアミン等の脂肪酸アミドアミン及びその塩;ステアロキシプロピルジメチルアミン等のアルキルエーテルアミン及びその塩又は四級塩;エチル硫酸長鎖分岐脂肪酸(12乃至31)アミノプロピルエチルジメチルアンモニウム、エチル硫酸ラノリン脂肪酸アミノプロピルエチルジメチルアンモニウム等の脂肪酸アミド型四級アンモニウム塩;ポリオキシエチレンアルキルアミン及びその塩又は四級塩;アルキルアミン塩;脂肪酸アミドグアニジウム塩;アルキルエーテルアミンモニウム塩;アルキルトリアルキレングリコールアンモニウム塩;ベンザルコニウム塩;ベンゼトニウム塩;塩化セチルピリジニウム等のピリジニウム塩;イミダゾリニウム塩;アルキルイソキノリニウム塩;ジアルキルモリホニウム塩;ポリアミン脂肪酸誘導体;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、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等のシリコーン系陽イオン性界面活性剤等;
両性界面活性剤としては、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。
本発明の増粘性組成物は、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、多価アルコール、水および有機酸とを含み、所望に応じて、脂肪酸、界面活性剤、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。
a)上記脂質ペプチド化合物と、多価アルコールを混合し、加熱して溶解液又は分散液(プレミックス相)を調製する工程
b)上記溶解液又は分散液(プレミックス相)を室温以上100℃未満の温度で加熱する工程
c)多価アルコール、水および有機酸を混合し、加熱して溶解液又は分散液(水相)を調製する工程
d)上記溶解液又は分散液(水相)を室温以上100℃未満の温度で加熱する工程
e)上記加熱されたプレミックス相と、上記加熱された水相とを混合し、上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、増粘性組成物を形成する工程
なお、脂肪酸、界面活性剤、その他添加剤は、a)工程において溶解液又は分散液(プレミックス相)の調製工程において添加してもよいし、c)工程において溶解液又は分散液(水相)の調製工程において添加してもよい。
また得られた増粘性組成物の総質量に対して、水は20質量%以上90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(水相)の総質量に対して、水は40質量%以上80質量%未満であることが好ましい。
この時の夫々の工程における加熱撹拌の時間は、用いる脂質ペプチド化合物や多価アルコール、有機酸ほかその他成分の種類、そしてそれらの配合量によって異なるが、通常5分から50分程度で溶解・分散可能である。
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フリー体の白色の結晶、26.9g(収率65%)を得た。
(アスコルビン酸増粘性組成物の調製1)
表1に示す組成物1乃至11を以下の手順で調整した。
プレミックス相の成分を、表1に示す配合量に従いサンプル管No.5(マルエム社製)に秤取した。また、水相の成分を、表1に示す配合量に従い、300mLトールビーカーに秤取した。次にプレミックス相と水相を加熱し、それぞれ70℃以上にした。続いてプレミックス相および水相を混合した後、攪拌放冷した。液温が40℃となったところで攪拌停止し、組成物サンプルとして調製した。
調製したサンプルの粘度を、粘度計(AND VIBRO VISCOMETER SU-1A)を用いて測定した。粘度値は、振動を与えて1分後の値を用いた。結果を表1に示す。表1中、Pal-GHは合成例1で得られた脂質ペプチド(N-パルミトイル-Gly-Hisフリー体)を意味し、BGは3-ブチレングリコールを意味する。
(アスコルビン酸増粘性組成物の調製2)
表2に示す組成物12乃至21を以下の手順で調整した。
プレミックス相の成分を、表2に示す配合量に従いサンプル管No.5(マルエム社製)に秤取した。また、水相の成分を、表2に示す配合量に従い、300mLトールビーカーに秤取した。次にプレミックス相と水相を加熱し、それぞれ70℃以上にした。プレミックス相および水相を混合した後、攪拌放冷した。液温が40℃となったところで攪拌停止し、組成物サンプルとして調製した。
調製したサンプルの粘度を、粘度計(AND VIBRO VISCOMETER SU-1A)を用いて測定した。粘度値は、振動を与えて1分後の値を用いた。結果を表2に示す。表2中、Pal-GHは合成例1で得られた脂質ペプチド(N-パルミトイル-Gly-Hisフリー体)を意味し、BGは3-ブチレングリコールを意味する。
Claims (8)
- 多価アルコール、水および有機酸と、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増粘性組成物。
- 少なくとも一種の脂肪酸を更に含む、請求項1に記載の増粘性組成物。
- 少なくとも一種の界面活性剤を更に含む、請求項1又は請求項2に記載の増粘性組成物。
- 前記脂肪酸が、ステアリン酸である、請求項2に記載の増粘性組成物。
- 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3に記載の増粘性組成物。
- 前記有機酸が、アスコルビン酸である請求項1乃至5のいずれか1項に記載の増粘性組成物。
- 多価アルコール、水および、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を含む、請求項1乃至6のいずれか1項に記載の増粘性組成物の製造の際の原料プレミックス。
- 少なくとも一種の脂肪酸を更に含む請求項7に記載のプレミックス。
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JP2016519303A JP6613486B2 (ja) | 2014-05-15 | 2015-05-14 | 脂質ペプチド型化合物を含有する増粘性組成物 |
KR1020167031281A KR20170002431A (ko) | 2014-05-15 | 2015-05-14 | 지질 펩티드형 화합물을 함유하는 증점성 조성물 |
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