WO2019139143A1 - 粉体を含む組成物 - Google Patents
粉体を含む組成物 Download PDFInfo
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- WO2019139143A1 WO2019139143A1 PCT/JP2019/000759 JP2019000759W WO2019139143A1 WO 2019139143 A1 WO2019139143 A1 WO 2019139143A1 JP 2019000759 W JP2019000759 W JP 2019000759W WO 2019139143 A1 WO2019139143 A1 WO 2019139143A1
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- acid
- extract
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- oil
- fatty acid
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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
-
- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives 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
- A61K8/72—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
- A61K8/88—Polyamides
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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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds 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
- 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
-
- 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
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
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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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/416—Quaternary ammonium compounds
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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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
-
- 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
- A61K2800/59—Mixtures
- A61K2800/596—Mixtures of surface active compounds
-
- 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
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Definitions
- the present invention relates to a composition comprising a powder.
- a paint used for paint applications such as paint and paint is one in which colored powder is dispersed in a medium such as water or an organic solvent.
- a solid substance generally called powder-concentrated masterbatch is used, and the desired paint can be obtained by dissolving and diluting this masterbatch using an appropriate medium.
- resin are reported as a matrix used when producing these masterbatches (patent document 1).
- the powder is dispersed using a polymer such as a resin, even though the dispersibility of the powder in the masterbatch is good, the masterbatch has poor compatibility with the medium, particularly an aqueous medium.
- processing such as vigorous stirring is required.
- distributes a high concentration powder dispersion easily in water can be applied also to manufacture of the concentrate of a mouthwash, for example.
- the problem to be solved by the present invention is to provide a composition which contains powders used for various applications such as paints and mouthwashes in a dispersed state, and diffuses the powders quickly in water. .
- the present inventors have determined that a composition comprising a powder, a specific lipid peptide type gelling agent, a fatty acid salt, an acidic low molecular weight compound and a surfactant. Upon application, it was found that the powder dispersed in the composition and that the powder diffused rapidly in water, completing the present invention.
- a lipid peptide type gelling agent comprising at least one of a compound represented by the following formula (1) or a pharmaceutically usable salt thereof, water, a fatty acid salt and , A composition containing an acidic low molecular weight compound, a surfactant, and a powder.
- 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.
- the fatty acid salt is butyric acid, valerate, capronic acid, enanthate, caprylate, pelargonate, caprate, laurate, myristate, pentadecylate, palmitate Salt, palmitoleate, margarate, stearate, oleate, bacerate, linoleate, (9, 12, 15) -linolenic acid, (6, 9, 12) -linolenic acid, Selected from the group consisting of eleostearate, tuberculostearate, arachidate, arachidonic acid, behenate, lignoceric acid salt, nervonic acid salt, ceroterate, montanate and myristate acid salt
- the composition according to the first aspect which is at least one fatty acid salt.
- a third aspect relates to the composition according to the first or second aspect, wherein the surfactant is an anionic or nonionic surfactant having a hydrocarbon chain having 11 or more carbon atoms.
- the present invention relates to the composition according to any one of the first to third aspects, wherein the acidic low molecular weight compound is a quaternary ammonium salt and / or a hydrochloride of an organic acid.
- the present invention relates to the composition according to any one of the first to fourth aspects, further containing a polyhydric alcohol.
- the present invention relates to the composition according to any one of the first to fifth aspects, which diffuses in water rapidly.
- a seventh aspect relates to the composition according to any one of the first to sixth aspects, which is a mouthwash.
- An eighth aspect relates to the composition according to any one of the first to sixth aspects, which is a liquid dentifrice.
- the present invention it is possible to provide a composition which contains powder in a dispersed state and which rapidly diffuses the powder in water.
- a desired powder concentrate a composition containing a desired powder
- water the concentrate
- the powder can be uniformly dispersed in water to the extent that external shaking is added.
- FIG. 1 is a photograph of a sample tube after gel preparation in Reference Example 1.
- FIG. 2 is a photograph of a sample tube showing that hydroxyapatite is dispersed in Example 2.
- FIG. 3 is a photograph of the tall beaker before stirring in Example 3.
- FIG. 4 is a photograph of a tall beaker under agitation in Example 3.
- FIG. 5 is a photograph of the tall beaker after stirring in Example 3.
- the present invention provides a lipid peptide type gelling agent comprising at least one of a compound represented by the following formula (1) or a pharmaceutically usable salt thereof, water, a fatty acid salt, and an acidic low molecular weight compound , A surfactant, and a composition containing powder.
- a compound represented by the following formula (1) or a pharmaceutically usable salt thereof water, a fatty acid salt, and an acidic low molecular weight compound , A surfactant, and a composition containing powder.
- lipid peptide type gelling agent As a lipid peptide type gelling agent used in the present invention, a compound represented by the following formula (1) (lipid peptide) or a pharmaceutically usable salt thereof (a lipid part as a hydrophobic part and a hydrophilic part) A low molecular weight compound having a peptide moiety 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. It is desirable that it is an aliphatic group.
- lipid moiety (acyl group) composed of a carbonyl group adjacent to R 1 include a lauroyl group, a dodecyl carbonyl group, a myristoyl group, a tetradecyl carbonyl group, a palmitoyl group, a margaroyl group, an oleoyl group, an eliidoyl group And linoleoyl group, stearoyl group, baccenoyl group, octadecyl carbonyl group, arachidoyl group, eicosyl carbonyl group, behenoyl group, erkanoyl group, docosyl carbonyl group, lignoselyl group, nervonoyl group and the like, with particular preference given to A lauroyl group, a myristoyl group, a palmitoyl group, a margalloyl group, a stearoyl group, an
- 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 which can have a branched chain having 1 or 2 carbon atoms means a branched chain having 1 to 4 carbon atoms in the main chain and 1 or 2 carbon atoms.
- R 2 is preferably a hydrogen atom or an alkyl group having a carbon number of 1 to 3 may have a branched chain of carbon atoms 1, more preferably a hydrogen atom.
- An alkyl group having 1 to 3 carbon atoms which may have a branched chain having 1 carbon atom means an alkyl group having 1 to 3 carbon atoms in the main chain and having a branched chain having 1 carbon atom.
- specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an i-butyl group or a sec-butyl group and the like, preferably a methyl group, an i-propyl group, It is an i-butyl group or a sec-butyl group.
- R 3 represents a — (CH 2 ) n —X group.
- n represents a number from 1 to 4
- X is an amino group, a guanidino group, a -CONH 2 group, or a 5-membered ring which may have 1 to 3 nitrogen atoms 6-membered ring or a fused heterocyclic ring composed of 5- and 6-membered rings.
- X is preferably an amino group, a guanidino group, a carbamoyl group (-CONH 2 group), a pyrrole group, an imidazole group, a pyrazole group or an indole group, 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, a 2-aminoethyl group, a 3-aminopropyl group, a 4-aminobutyl group, a carbamoylmethyl group, a 2-carbamoylethyl group, a 3-carbamoyl group.
- a lipid peptide particularly suitable as a lipid peptide type gelling agent is a compound formed from the following lipid moiety and peptide moiety (amino acid aggregate moiety).
- amino acid aggregate moiety alanine (Ala), asparagine (Asn), glutamine (Gln), glycine (Gly), histidine (His), isolocin (Ile), leucine (Leu), lysine (Lys), tryptophan (Trp) And 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-
- lauroyl-Gly-His lauroyl-Ala-His
- myristoyl-Gly-His myristoyl-Ala-His
- palmitoyl-Gly-His palmitoyl-Ala-His
- stearoyl-Gly-His stearoyl-Ala -His is mentioned.
- the content of the lipid peptide type gelling agent is, for example, 0.01% by mass to 1% by mass, or 0.01% by mass or more and less than 1% by mass, preferably 0 based on the total mass of the composition.
- the content is 0.55% by mass to 0.5% by mass, more preferably 0.05% by mass to 0.3% by mass, for example, 0.05% by mass to 0.2% by mass.
- the lipid peptide type gelling agent used in the present invention comprises at least one of the compound represented by the above formula (1) (lipid peptide) or a pharmaceutically usable salt thereof, and these compounds may be used alone. Or in combination of two or more.
- the fatty acid salt used in the present invention is not particularly limited, and for example, a general-purpose fatty acid salt can be used as an additive for cosmetics and pharmaceuticals.
- fatty acid salt examples include butyric acid salt, valerate salt, capronic acid salt, enanthate, caprylate, pelargonate, caprate, laurate, myristate, pentadecylate, palmitate , Palmitoleate, margaric acid, stearate, oleate, bacerate, linoleate, (9, 12, 15) -linolenic acid, (6, 9, 12) -linolenic acid, aire
- laurate, myristate, palmitate, stearate or oleate is used. More preferred are myristate, palmitate or stearate.
- a sodium salt or a potassium salt is mentioned, for example, Especially a sodium salt is preferable.
- the content of the fatty acid salt is, for example, 0.01% by mass to 30% by mass, preferably 0.02% by mass to 10% by mass, more preferably 0.02% by mass, relative to the total mass of the composition. % To 2% by mass.
- the fatty acid salt used for this invention can be used individually or in combination of 2 or more types.
- the acidic low molecular compound used in the present invention is, for example, an acidic compound having a molecular weight of 200 to 600. Among them, quaternary ammonium salts or hydrochlorides of organic acids are preferable as the acidic low molecular weight compounds used in the present invention.
- Examples of the quaternary ammonium salt include cetyl pyridinium chloride, benzalkonium chloride, benzethonium chloride, decarinium chloride, dimethylethyl benzyl ammonium chloride, didecyl dimethyl ammonium chloride, didecyl dimethyl ammonium adipate, didecyl dimethyl ammonium gluconate, Mention may be made of decyl monomethyl hydroxyethyl ammonium adipate, didecyl dimethyl ammonium propionate and didecyl mono methyl hydroxyethyl ammonium sulfonate and the like.
- Preferred are cetyl pyridinium chloride, benzalkonium chloride, decalinium chloride or benzethonium chloride. More preferably, it is cetyl pyridinium chloride.
- lidocaine hydrochloride As hydrochlorides of the above-mentioned organic acids, lidocaine hydrochloride, histidine hydrochloride, meplarchine hydrochloride, alkyldiaminoethylglycine hydrochloride, cysteine hydrochloride, triethanolamine hydrochloride, triethanolamine, 2,2'-azobis (2-methylpropionamidine) dihydrochloride and There may be mentioned 2,2'-bis (2-imidazolin-2-yl) [2,2'-azobispropane] • hydrochloride and the like. More preferably, it is lidocaine hydrochloride.
- the content of the acidic low molecular weight compound is, for example, 0.01% by mass to 30% by mass, preferably 0.02% by mass to 10% by mass, more preferably 0 based on the total mass of the composition. It is .05 mass% to 2 mass%.
- the acidic low molecular weight compound used for this invention can be used individually or in combination of 2 or more types.
- the surfactant used in the present invention is preferably an anionic or nonionic surfactant having a hydrocarbon chain having 11 or more carbon atoms, and an anionic or nonionic surfactant having a hydrocarbon chain having 13 or more carbon atoms.
- Agent is more preferable, an anionic or nonionic surfactant having a hydrocarbon chain having 15 or more carbon atoms is further preferable, and an anionic or nonionic surfactant having a hydrocarbon chain having 17 or more carbon atoms is particularly preferable .
- anionic surfactant which has a C11 or more hydrocarbon chain
- Fatty acid salts such as potassium laurate and potassium myristate
- Alkyl sulfate ester salts such as sodium lauryl sulfate, triethanolamine lauryl sulfate, ammonium lauryl sulfate etc.
- nonionic surfactants having a hydrocarbon chain having 11 or more carbon atoms laureth (polyoxyethylene lauryl ether), ceteth (polyoxyethylene cetyl ether), steareth (polyoxyethylene stearyl ether), behenes
- Polyoxyethylene alkyl ethers of various polyoxyethylene addition numbers such as (polyoxyethylene behenyl ether), isosteares (polyoxyethylene isostearyl ether), octyl dodeces (polyoxyethylene octyl dodecyl ether), etc .; polyoxyethylene Alkyl phenyl ether; polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisos Castor oil and hydrogenated castor oil derivatives such as alate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester, polyoxyethylene hydrogenated castor oil and
- the content of surfactant is, for example, 0.01% by mass to 10% by mass, preferably 0.01% by mass to 7% by mass, more preferably 0.1% by mass, with respect to the total mass of the composition. It is 01% to 5% by mass, for example, 0.02% to 3% by mass.
- surfactant used for this invention can be used individually or in combination of 2 or more types.
- the powder used in the present invention is not particularly limited.
- As powder mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, pyromica, biotite, permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, silicate Barium, calcium silicate, magnesium silicate, strontium silicate, metal salt of tungstate, magnesium, zeolite, barium sulfate, calcined calcium sulfate, calcium phosphate such as tricalcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder, bentonite, smectite , Clay, mud, metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, bengara, yellow iron oxide, black iron oxide, ultramarine blue, bitumen, carbon black, oxidized Tan, fine particles and ultrafine
- the content of the powder is, for example, 25% by mass or less, preferably 20% by mass or less, more preferably 15% by mass or less, based on the total mass of the composition.
- the lower limit of the content of the powder is not particularly limited, and is, for example, about 0.001 mass%.
- the powder used for this invention may be used individually or in combination of 2 or more types.
- the composition of the present invention may further contain a polyhydric alcohol.
- the polyhydric alcohol is an alcohol having a valence of 2 or more and, for example, propylene glycol, 1,3-butanediol, 2-ethyl-1,3-hexanediol, glycerin, isopentyldiol, ethylhexanediol, erythrulose , Ozonized glycerin, caprylyl glycol, glycol, (C15-18) glycol, (C20-30) glycol, glycerin, diethylene glycol, diglycerin, dithiaoctanediol, DPG, thioglycerin, 1,10-decanediol, Silene glycol, triethylene glycol, tilylmethyl gidooxymethyl cyclohexanol, phytantriol, phenoxypropanediol, 1,2-butanedi
- the content thereof when the polyhydric alcohol is contained, the content thereof can be, for example, 1% by mass to 60% by mass, preferably 1% by mass to 30% by mass, with respect to the total mass of the composition.
- the polyhydric alcohol when a polyhydric alcohol is contained, the polyhydric alcohol may be used alone or in combination of two or more.
- composition of the present invention can contain, if necessary, a cosmetic additive, an additive for quasi-drugs, an additive usable as a pharmaceutical additive, and the like.
- Additives such as physiologically active substances and functional substances to be added to skin external preparations such as cosmetics, quasi-drugs and medicines include, for example, pigments, oily bases, moisturizers, feel improvers, and surfactants other than the above.
- Agents polymers, thickeners / gelling agents, solvents, antioxidants, reducing agents, oxidizing agents, preservatives, antibacterial agents, bactericides, chelating agents, pH adjusters, acids, alkalis, inorganic salts, UV absorbers Whitening agents, vitamins and their derivatives, hair growth agents, circulation promoters, stimulants, hormones, anti-wrinkle agents, anti-aging agents, tempering agents, cooling agents, warming agents, wound healing promoters, stimulation Relievers, Analgesics, Cell Activators, Plant / Animals / Microbial Extracts, Antipruritics, Exfoliants, Solubilisers, Antiperspirants, Refreshants, Convulsants, Enzymes, Nucleic Acids, Flavors, Pigments, Colorants, Dyes, Anti-inflammatory Agent, anti-inflammatory agent, anti-asthma, anti-chronic obstructive pulmonary disease, anti-allergy, immune modulation , Anti-infective agents and antifungal
- inorganic white pigments such as titanium dioxide and zinc oxide
- inorganic red pigments such as red iron oxide (bengal) and iron titanate
- inorganic brown pigments such as ⁇ -iron oxide; yellow iron oxide, yellow earth and the like Inorganic yellow pigments
- inorganic black pigments such as black iron oxide and low-order titanium oxide
- inorganic violet pigments such as mango violet and cobalt violet
- inorganic green pigments such as chromium oxide, chromium hydroxide and cobalt titanate
- Inorganic blue pigments such as bitumen
- talc sericite, mica
- Extender pigments such as kaolin, calcium carbonate, magnesium carbonate, anhydrous silicic acid, barium sulfate, aluminum hydroxide; Rumi bromide
- higher (polyhydric) alcohols such as oleyl alcohol, jojoba alcohol, chymyl alcohol, cerakyl alcohol, batyl alcohol, hexyldecanol, isostearyl alcohol, 2-octyldodecanol, dimer diol, etc .; benzyl alcohol etc.
- Alcohols and derivatives thereof isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linoleic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, Anteisohenicoic acid, long chain branched fatty acid, dimer acid, hydrogenated dimer acid, etc .; liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, ⁇ -olefin Rigomers, polyisobutenes, hydrogenated polyisobutenes, polybutenes, squalanes, squalanes derived from olives, hydrocarbons such as squalene, squalene, vaseline, solid paraffin, etc .; candelilla wax, carnauba wax, rice wax, rice wax
- Humectants and feel improvers include polyols such as glycerin, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, dipropylene glycol, polypropylene glycol, ethylene glycol / propylene glycol copolymer, etc.
- Glycol alkyl ethers such as diethylene glycol monoethyl ether (ethoxy diglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol dibutyl ether; (Eicosane diacid / tetradecanedioic acid) polyglyceryl-10, tetradecane -Soluble esters such as polyglyceryl acid 10; sorbitol, xylitol, erythritol, man Sugar alcohols such as tall and maltitol; glucose, fructose, galactose, mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, trehalose, lactose, raffinose, gluconic acid, glucuronic acid, cyclodextrins ( ⁇ -, ⁇
- Peptides silylated peptides; lactic acid bacteria culture solution, yeast extract, eggshell membrane protein, bovine submandibular mucin, hypotaurine, sesame lignan glycoside, glutathione, Albumin, whey, choline chloride, phosphoryl choline; placenta extract, air lastin, collagen, aloe extract, hamamelis water, hemerica water, kamomira extract, licorice extract, licorice extract, silk extract, lice extract, yarrow extract, eucalyptus extract And extracts of animals and plants such as Meriloto extract, natural ceramides (types 1, 2, 3, 4, 5, 6), hydroxyceramides, pseudoceramides, glycosphingolipids, ceramides, and ceramides containing saccharides and ceramides. Preferred is mentioned.
- surfactant cationic surfactant, amphoteric surfactant, polymeric surfactant etc. are mentioned as a preferable thing.
- cationic surfactants alkyltrimethylammonium chlorides such as behentrimonium chloride, stealtrimonium chloride, cetrimonium chloride, lauryltrimonium chloride and the like; stearyltrimonium bromide and the like Alkyl trimethyl ammonium bromide; dialkyl dimethyl ammonium chloride such as distealyl dimonium chloride, dicoco di monium chloride; fatty acid amide amines such as stearamidopropyl dimethyl amine, stearamide ethyl diethylamine and salts thereof; alkyl ether amines such as stearoxy propyl dimethyl amine And salts or quaternary salts thereof; ethyl sulfate long-chain branched fatty acids (12 to 31)
- N-alkyl-N, N-dimethyl amino acid betaines such as lauryl betaine (lauryl dimethylaminoacetic acid betaine); fatty acid amide alkyl-N such as cocamidopropyl betaine and lauramidopropyl betaine , N-dimethyl amino acid betaines; imidazoline type betaines such as sodium cocoamphoacetate, sodium lauroamphoacetate; alkyl sulfobetaines such as alkyl dimethyl taurine; sulfuric acid type betaines such as alkyl dimethylamino ethanol sulfate esters; such as alkyl dimethylamino ethanol phosphate esters Phosphate type betaine; Sphingophospholipids such as phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, sphingomyelin, lysolecithin, hydrogenated soybean phospholipid Partially
- polymers, thickeners and gelling agents examples include guar gum, locust bean gum, queen seeds, carrageenan, galactan, gum arabic, gum arabic, tara gum, tamarind, farcereran, karaya gum, troy roy, caragam, tragant gum, pectin, pectate and sodium Salts such as salts, salts such as alginic acid and sodium salts, mannan starches such as rice, corn, potato, wheat etc.
- xanthan gum dextran, succinoglucan, curdlan, hyaluronic acid and its salts, xanthan gum, pullulan, gellan gum, chitin Chitosan, agar, cassava extract, chondroitin sulfate, casein, collagen, gelatin, albumin; methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypro Cellulose such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose and its sodium salt, methyl hydroxypropyl cellulose, cellulose sodium sulfate, dialkyldimethyl ammonium cellulose, crystalline cellulose, cellulose powder and its derivatives; soluble starch, carboxymethyl starch, Starch polymers such as methylhydroxypropyl starch and methyl starch, starch derivatives such as hydroxypropyltrimonium chloride chloride and corn starch aluminum octenyl succinic acid; alginic acid
- lower alcohols such as ethanol, 2-propanol (isopropyl alcohol), butanol and isobutyl alcohol; glycols such as propylene glycol, diethylene glycol, dipropylene glycol and isopentyl diol; diethylene glycol monoethyl ether (ethoxy diglycol) Glycol ethers such as ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, triethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, propylene glycol monoethyl ether, dipropylene glycol monoethyl ether; ethylene glycol monoethyl ether Acetate, diethylene glycol Glycol ether esters such as ethyl ether acetate and propylene glycol monoethyl ether acetate; Glycol esters such as diethoxyethyl succinate and ethylene glycol
- Antioxidants include tocopherols such as tocopherol (vitamin E) and tocopherol acetate; BHT, BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and / or its derivatives; erythorbic acid and its derivatives; Sulfites such as sodium sulfite; bisulfites such as sodium bisulfite; thiosulfates such as sodium thiosulfate; metabisulfite; thiotaurine, hypotaurine; thioglycerol, thiourea, thioglycolic acid, cysteine hydrochloride Can be mentioned as
- thioglycolic acid As a reducing agent, thioglycolic acid, cysteine, cysteamine etc. are mentioned as a preferable thing.
- oxidizing agent hydrogen peroxide water, ammonium persulfate, sodium bromate, percarbonate and the like are mentioned as preferable.
- hydroxybenzoic acids such as methylparaben, ethylparaben, propylparaben, butylparaben and salts or esters thereof; salicylic acid; sodium benzoate; phenoxyethanol; methyl chloroisothiazolinone, methylisothiazo Isothiazolinone derivatives such as linone; imidazolinium urea; dehydroacetic acid and salts thereof; phenols; halogenated bisphenols such as triclosan, acid amides, quaternary ammonium salts; trichlorocarbanide, zinc pyrithione, benzalkonium chloride, chloride Benzethonium, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophen, hinokitiol; phenol, isopropyl phenol, cresol, Mall,
- edetate ethylenediamine tetraacetate
- EDTA EDTA
- 2Na EDTA3Na
- EDTA4Na EDTA4Na
- hydroxyethylethylenediamine triacetate such as HEDTA3Na
- pentethate diethylenetriamine pentaacetate
- phytic acid etidronate etc.
- pH adjusters / acids / alkalis such as ascorbic acid, citric acid, sodium citrate, lactic acid, sodium lactate, potassium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric acid, fumaric acid, phosphoric acid, Hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propane Diol, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia, guanidine carbonate and ammonium carbonate are mentioned as preferred.
- acids / alkalis such as ascorbic acid, citric acid, sodium citrate, lactic acid, sodium lactate, potassium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric
- sodium chloride-containing salts such as sodium chloride, common salt, rock salt, sea salt, natural salt, etc .
- potassium chloride aluminum chloride, calcium chloride, magnesium chloride, zinc oxide, ammonium chloride
- sodium phosphates such as phosphoric acid 1Na ⁇ 2Na ⁇ 3Na, phosphoric acid Preferred are potassiums, calcium phosphates and magnesium phosphates.
- UV absorbers include paraaminobenzoic acid, paraglyceryl monoglyceryl ester of paraaminobenzoic acid, ethyl ester of N, N-dipropoxyparaaminobenzoic acid, ethyl ester of N, N-diethoxyparaaminobenzoic acid, ethyl N, N-dimethylparaaminobenzoate
- Benzoic acid ultraviolet absorbers such as ester, N, N-dimethyl paraaminobenzoic acid butyl ester, N, N-dimethyl paraaminobenzoic acid methyl ester;
- Anthranilic acid ultraviolet absorbers such as homomentyl-N-acetyl anthranilate
- salicylic acid And salicylic acid such as sodium salt, amyl salicylate, menthyl salicylate, homomentyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate,
- hydroquinone glycosides such as arbutin and ⁇ -arbutin and esters thereof; ascorbic acid phosphate ester salt such as ascorbic acid, ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt, ascorbic acid Ascorbic acid fatty acid esters such as tetraisopalmitate esters, 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 sulfuric acid esters, tocopheryl ascorbic acid phosphate Ascorbic acid derivatives such as: kojic acid, ellagic acid, tranexamic acid and its derivatives, ferulic acid and its derivatives, placenta extract, glutathione, oryzanol, butyl res Shinoru, oil-soluble Kamomiraekisu, oil-soluble lic
- Vitamins and derivatives thereof include vitamin A such as retinol, retinol acetate, retinol palmitate, thiamine hydrochloride, thiamine sulfate, riboflavin acetate, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, Flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinic acid such as nicotinamide and benzyl nicotinate, and vitamin B groups such as choline; vitamin C such as ascorbic acid and salts thereof such as sodium; vitamin D; ⁇ , ⁇ , Vitamin E such as ⁇ , ⁇ , ⁇ -tocopherol; Other vitamins such as pantothenic acid, biotin etc.
- vitamin A such as retinol, retinol acetate, retinol palmitate, thiamine hydro
- the fatty acid ester, ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, tocopherol phosphate, tocotrienol, various other vitamin derivatives Is mentioned as a preferable thing.
- estradiol, estrone, ethynyl estradiol, cortisone, hydrocortisone, prednisone etc. are mentioned as a preferable thing.
- Other medicinal agents such as anti-wrinkle agent, anti-aging agent, tempering agent, cooling agent, warming agent, wound healing promoting agent, irritation reducing agent, analgesia agent, cell activator and the like include retinols, retinoic acid, retinoic acid Acid tocopheryl; lactic acid, glycolic acid, gluconic acid, fruit acid, salicylic acid and derivatives thereof such as glycosides / esterified products, hydroxycapric acid, long chain ⁇ -hydroxy fatty acid, long chain ⁇ -hydroxy fatty acid cholesteryl ⁇ - or ⁇ -hydroxy acids and their derivatives; ⁇ -aminobutyric acid, ⁇ -amino- ⁇ -hydroxybutyric acid; carnitine; carnosine; creatine; ceramides, sphingo
- coenzyme Q10 coenzyme Q10, carotene, lycopene , Astaxanthin, lutein, ⁇ -lipoic acid, platinum nanocolloid, fullerenes, etc.
- hesperidin and glycosides Derivatives of hesperidin and glycosides; lignan glycosides; licorice extract related substances such as glabridin, glabren, liquiritin and isoliquiritin; lactoferrin; gingerol and zingerol; flavoring substances such as menthol and cedrol; Vanillin and the like and derivatives; Insect repellents such as diethyltoluamide; and complexes of physiologically active substances and cyclodextrins.
- plant / animal / microbe extracts examples include iris extract, ashitaba extract, asunaro extract, asparagus extract, avocado extract, amacha extract, almond extract,retea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract and ginkgo extract , Ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, umbilical root extract, Egeria extract, Echinacea leaf extract, Einacea leaf extract, Aedesium extract, Augan extract, Auaba extract, Auaba extract, Auula extract, a barley extract, a ginseng extract, a ginseng extract, an apricot extract, an apricot extract , Dutch mustard extract, orange extract, dried sea water, seaweed extract, persimmon leaf extract, persimmon leaf extract, hydrolyzed elastin, hydrolyzed wheat powder, water content Silk, Cucklin Extract, Kamomila Extract, Oil-soluble Kamomila Extract, Carrot Extract, Ka
- antipruritic agents examples include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, substance-P inhibitors and the like.
- exfoliating agent for solubilization examples include salicylic acid, sulfur, resorcinol, selenium sulfide, pyridoxine and the like.
- chlorhydroxy aluminum, aluminum chloride, zinc oxide, zinc paraphenol sulfonate etc. are mentioned.
- cooling agent examples include menthol, methyl salicylate and the like.
- citric acid tartaric acid, lactic acid, aluminum potassium sulfate, tannic acid and the like can be mentioned.
- enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, protease and the like.
- nucleic acids As nucleic acids, ribonucleic acid and its salts, deoxyribonucleic acid and its salts, and adenosine triphosphate disodium are mentioned as preferable.
- Dyes / Colorants / Dye Brown No. 201, Black No. 401, Purple No. 201, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 202, Blue No. 203, Blue No. 203, Blue No. 204, Blue No. 205, Blue 403, Blue 404, Green 201, Green 202, Green 204, Green 205, Green 3, Green 401, Green 402, Red 102, Red 102, Red 104-1, Red 105-1, red 106, red 2, red 201, red 202, red 203, red 204, red 205, red 206, red 207, red 208, red 208, red 213, red No.
- Anti-inflammatory agents and anti-inflammatory agents include glycyrrhizinic acid and derivatives thereof, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, ketoprofen, ibuprofen, diclofenac, loxoprofen, cericosquib, infliximab, etanercept, zinc oxide, acetic acid hydrocortisone. Plant extracts such as prednisone, diphedramine hydrochloride, chlorpheniramine maleate, and peach leaf extract and mulberry leaf extract are preferred.
- immuno-regulatory agents such as aminophylline, theophyllines, steroids (fluticasone, beclomethas
- oseltamivir, zanamivir and itraconazole are mentioned as preferable ones.
- cosmetic raw material standard cosmetic type compounding ingredient standard
- Japan Cosmetics Industry Association Association ingredient display name list INCI dictionary (The International Cosmetic Ingredient Dictionary and Handbook), quasi-drug raw material standard, Japanese Pharmacopoeia, pharmaceutical additive standard Ingredients described in Food Additives Official Standards, etc.
- Japanese and other foreign patent publications and patent publication gazettes including published gazettes / republications
- the international patent classification IPC belongs to the classification of A61K7 and A61K8. It is possible to contain known cosmetic ingredients, pharmaceutical ingredients, food ingredients, etc. in the known combination and blending ratio / blending amount, such as the ingredients mentioned above.
- composition of the present invention comprises a lipid peptide type gelling agent comprising at least one of the compound represented by the above formula (1) or a pharmaceutically usable salt thereof, water, a fatty acid salt, and an acid. It can be produced by mixing low molecular weight compounds, surfactants, powders, and, if desired, other additives such as polyhydric alcohols.
- the composition of the present invention is produced, for example, by the following steps. a) mixing a lipid peptide type gelling agent, a fatty acid salt, and water to prepare a premix (aqueous composition); b) mixing the premix obtained in step a), an acidic low molecular weight compound, and a surfactant to prepare a mixed solution; c) mixing the mixed solution obtained in step b) with powder to obtain the composition of the present invention.
- polyhydric alcohols and other additives may be added in the step a), may be added in the step b), or may be added in the step c).
- the solution may be heated at the time of mixing, and the heating temperature is preferably 40 ° C. to 90 ° C., more preferably 50 ° C. to 90 ° C., for example 80 ° C.
- stirring is performed.
- the heating and stirring time in each step at this time varies depending on the type and amount of each component used, but is usually about 1 minute to about 120 minutes.
- the heated solution may be left to cool by stirring, cooling by stirring or a combination thereof before proceeding to the next step.
- room temperature for example, room temperature to 80 ° C., room temperature to 60 ° C., or room temperature to 40 ° C. or so.
- composition of the present invention is suitable for a concentrate to be used by diluting at the time of use, and can be used, for example, in paints, cosmetics, pharmaceuticals, quasi-drugs, foods and the like.
- the composition of the present invention is preferably used as an oral composition such as a liquid dentifrice or a mouthwash, which is used as a concentrated type and diluted at the time of use.
- Synthesis Example 1 Synthesis of lipid peptide (N-palmitoyl-Gly-His)
- the lipid peptide type compound used in this example was synthesized by the method shown below. In a 500 mL four-necked flask, 14.2 g (91.6 mmol) of histidine, 30.0 g (91.6 mmol) of N-palmitoyl-Gly-methyl, and 300 g of toluene are charged, and sodium methoxide as a base 28% methanol solution 35.3 g (183.2 mmol) was added and heated to 60 ° C. with an oil bath and stirring was continued for 1 hour.
- the solid obtained here was dissolved in a mixed solution of 600 g of water and 750 g of methanol, and 30.5 mL (183.2 mmol) of 6 N hydrochloric acid was added thereto to neutralize it to precipitate a solid, which was filtered.
- the obtained solid was dissolved in a mixed solution of 120 g of tetrahydrofuran and 30 g of water at 60 ° C., 150 g of ethyl acetate was added, and the mixture was cooled to 60 ° C. to 30 ° C. Thereafter, the precipitated solid was filtered.
- the solid obtained 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 is washed with 120 g of water, filtered and dried under reduced pressure, and white crystals of N-palmitoyl-Gly-His free form (hereinafter, also simply referred to as Pal-GH), 26.9 g (yield 65) %) Got.
- Preparation Example 1 Preparation of Premix Add Pal-GH, stearic acid, sodium hydroxide, 1,3-butanediol and water as additives to a 300 mL beaker in the proportions shown in Table 1 below, and keep the liquid temperature at 80 ° C for 20 minutes to 90 minutes at 300 rpm. Heating and stirring were performed. After that, the heating was stopped, and after stirring and allowed to cool at 300 rpm for 1 hour, the water of the evaporation was replenished and stirring was further performed at 300 rpm for 1 minute. Then, it was left to stand overnight at room temperature to prepare a TW-01W premix.
- Softtilt AS-L Stairoyl sodium sodium manufactured by NOF Corporation: Musashino Chemical Laboratory Co., Ltd.
- Magbiobride MG-T NOF Corporation 12-hydroxystearic acid: Tokyo Chemical Industry Co., Ltd.
- 10 % CPC aqueous solution prepared by dissolving in pure water so that the concentration of hexadecyl pyridinium chloride monohydrate (manufactured by Wako Pure Chemical Industries, Ltd.) becomes 10 wt%.
- 10% lidocaine hydrochloride aqueous solution prepared by dissolving in pure water so that the concentration of lidocaine hydrochloride (Nisshin Pharmaceutical Co., Ltd.) becomes 10 wt%.
- Example 1 and Example 2 and Comparative Example 1 Dispersion Evaluation of Powder
- Each composition was weighed according to Table 3, and the composition was prepared according to the procedure shown below.
- the TW-01W premix was heated to 80 ° C.
- phase A was heated to 80.degree.
- stirring and cooling were performed.
- the liquid temperature reached 50 ° C.
- phase B was added, and stirring and cooling were further performed until the liquid temperature reached 40 ° C.
- the dispersibility of hydroxyapatite was evaluated as x when hydroxyapatite was precipitated after preparation of the composition.
- the hydroxyapatite was maintaining dispersion, it was set as O.
- a photograph of a sample tube showing that hydroxyapatite is dispersed in Example 2 is shown in FIG.
- Hydroxyapatite Made by Taihei Kagaku Sangyo Co., Ltd.
- Example 3 Evaluation of dispersibility of powder-containing composition
- a 300 mL tall beaker 190 g of pure water was weighed, and 10 g of the composition of Example 2 was added thereto. After stirring this for 2 minutes at 197 rpm using NEO SHAKER (made by As One Co., Ltd.), when the dispersibility was visually confirmed, the gel lump was not seen but it was disperse
- FIG. 3 is a photograph of the tall beaker before agitation
- Fig. 4 is a photograph of the tall beaker during agitation
- Fig. 5 is a photograph of the tall beaker after agitation.
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Abstract
Description
これらのマスターバッチを作る際に用いられるマトリックスとしては、樹脂を用いる例が多く報告されている(特許文献1)。
しかしながら、樹脂等の高分子を用いて粉体を分散させた場合は、マスターバッチ中の粉体の分散性は良好でも、該マスターバッチは媒体、特に水系の媒体との相溶性が悪く、該マスターバッチを水中に均一に分散させるためには、激しく撹拌する等の処理が必要となる。
また、高濃度の粉体分散物を、容易に水中に分散させる処方は、例えば、口腔洗浄剤の濃縮液の製造にも応用することができる。
第2観点として、前記脂肪酸塩が酪酸塩、吉草酸塩、カプロン酸塩、エナント酸塩、カプリル酸塩、ペラルゴン酸塩、カプリン酸塩、ラウリン酸塩、ミリスチン酸塩、ペンタデシル酸塩、パルミチン酸塩、パルミトレイン酸塩、マルガリン酸塩、ステアリン酸塩、オレイン酸塩、バクセン酸塩、リノール酸塩、(9,12,15)-リノレン酸塩、(6,9,12)-リノレン酸塩、エレオステアリン酸塩、ツベルクロステアリン酸塩、アラキジン酸塩、アラキドン酸塩、ベヘン酸塩、リグノセリン酸塩、ネルボン酸塩、セロチン酸塩、モンタン酸塩及びメリシン酸塩からなる群から選択される少なくとも一種の脂肪酸塩である、第1観点に記載の組成物に関する。
第3観点として、前記界面活性剤が炭素原子数11以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤である、第1観点又は第2観点に記載の組成物に関する。
第4観点として、前記酸性の低分子化合物が第4級アンモニウム塩及び/又は有機酸の塩酸塩である、第1観点乃至第3観点のいずれかに記載の組成物に関する。
第5観点として、更に多価アルコールを含有する、第1観点乃至第4観点のいずれかに記載の組成物に関する。
第6観点として、水中で速やかに拡散する、第1観点乃至第5観点のいずれかに記載の組成物に関する。
第7観点として、口腔洗浄剤である、第1観点乃至第6観点のいずれかに記載の組成物に関する。
第8観点として、液状歯磨剤である、第1観点乃至第6観点のいずれかに記載の組成物に関する。
特に、本発明によれば、所望の粉体の濃縮物(所望の粉体を含む組成物)を水中へ投入、又は、当該濃縮物(当該組成物)へ水を添加した際に、激しく撹拌することなく、外部からの振盪を加える程度で、当該粉体を、水中において、均一に拡散させることができる。
以下、各成分について説明する。
本発明に用いる脂質ペプチド型ゲル化剤としては、下記式(1)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と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。
なお、本発明に用いられる脂質ペプチド型ゲル化剤は、上記式(1)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、又は二種以上を組み合わせて用いることができる。
本発明に用いる脂肪酸塩としては特に制限されず、例えば、化粧品や医薬品の添加剤として汎用の脂肪酸塩を使用することができる。
なお、本発明に用いられる脂肪酸塩は単独で、又は二種以上を組み合わせて用いることができる。
本発明に用いる酸性の低分子化合物は、例えば、分子量が200乃至600である酸性の化合物である。その中でも、本発明に用いる酸性の低分子化合物としては、第4級アンモニウム塩又は有機酸の塩酸塩が好ましい。
なお、本発明に用いられる酸性の低分子化合物は単独で、又は二種以上を組み合わせて用いることができる。
本発明に用いる界面活性剤としては、炭素原子数11以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤が好ましく、炭素原子数13以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤がより好ましく、炭素原子数15以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤がさらに好ましく、炭素原子数17以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤が特に好ましい。
なお、本発明に用いられる界面活性剤は単独で、又は二種以上を組み合わせて用いることができる。
本発明に用いられる粉体としては、特に限定されるものではない。
粉体としては、マイカ、タルク、カオリン、セリサイト、モンモリロナイト、カオリナイト、雲母、白雲母、金雲母、合成雲母、紅雲母、黒雲母、パーミキュライト、炭酸マグネシウム、炭酸カルシウム、ケイ酸アルミニウム、ケイ酸バリウム、ケイ酸カルシウム、ケイ酸マグネシウム、ケイ酸ストロンチウム、タングステン酸金属塩、マグネシウム、ゼオライト、硫酸バリウム、焼成硫酸カルシウム、リン酸三カルシウム等のリン酸カルシウム、弗素アパタイト、ヒドロキシアパタイト、セラミックパウダー、ベントナイト、スメクタイト、粘土、泥、金属石鹸(例えば、ミリスチン酸亜鉛、パルミチン酸カルシウム、ステアリン酸アルミニウム)、炭酸カルシウム、ベンガラ、黄酸化鉄、黒酸化鉄、群青、紺青、カーボンブラック、酸化チタン、微粒子及び超微粒子酸化チタン、酸化亜鉛、微粒子及び超微粒子酸化亜鉛、アルミナ、シリカ、煙霧状シリカ(超微粒子無水ケイ酸)、雲母チタン、魚鱗箔、窒化ホウ素、ホトクロミック顔料、合成フッ素金雲母、微粒子複合粉体、金、銀、プラチナ、アルミニウム等の各種の大きさ・形状の無機粉体、及び、これらをハイドロジェンシリコーン、環状ハイドロジェンシリコーン等のシリコーン若しくはその他のシラン若しくはチタンカップリング剤等の各種表面処理剤で処理を行って疎水化若しくは親水化した粉体等の無機粉体;デンプン、セルロース、ナイロンパウダー、ポリエチレン末、ポリメタクリル酸メチル末、ポリスチレン末、スチレンとアクリル酸の共重合体樹脂粉末、ポリエステル末、ベンゾグアナミン樹脂粉末、ポリエチレンテレフタレート・ポリメチルメタクリレート積層末、ポリエチレンテレフタレート・アルミニウム・エポキシ積層末等、ウレタン粉末、シリコーン粉末、テフロン(登録商標)粉末等の各種の大きさ・形状の有機系粉体及び表面処理粉体、有機無機複合粉体が好ましいものとして挙げられる。
なお、本発明に用いられる粉体は単独で、又は二種以上を組み合わせて用いられ得る。
本発明の組成物は、さらに多価アルコールを含んでいてもよい。
上記多価アルコールとは、2価以上のアルコールであり、例えば、プロピレングリコール、1,3-ブタンジオール、2-エチル-1,3-ヘキサンジオール、グリセリン、イソペンチルジオール、エチルヘキサンジオール、エリスルロース、オゾン化グリセリン、カプリリルグリコール、グリコール、(C15-18)グリコール、(C20-30)グリコール、グリセリン、ジエチレングリコール、ジグリセリン、ジチアオクタンジオール、DPG、チオグリセリン、1,10-デカンジオール、デシレングリコール、トリエチレングリコール、チリメチルギドロキシメチルシクロヘキサノール、フィタントリオール、フェノキシプロパンジオール、1,2-ブタンジオール、2,3-ブタンジオール、ブチルエチルプロパンジオール、1,2-ヘキサンジオール、ヘキシレングリコール、ペンチレングリコール、メチルプロパンジオール、メンタンジオール、ラウリルグリコール及びポリプロピレングリコールが挙げられる。
なお、本発明において、多価アルコールを含む場合、多価アルコールは単独で、又は二種以上を組み合わせて用いられ得る。
本発明の組成物は、必要に応じて一般に化粧品用添加剤や、医薬部外品用添加剤及び医薬用添加剤として使用可能な添加剤などを含むことができる。化粧品、医薬部外品又は医薬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、例えば顔料、油性基剤、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、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、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、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。
これらその他添加剤の含有量は、その種類によって種々変化し得るが、組成物の総質量に対して、例えば0.001質量%乃至20質量%、あるいは0.01質量%乃至10質量%程度とすることができる。
顔料としては、二酸化チタン、酸化亜鉛等の無機白色顔料;赤酸化鉄(ベンガラ)、チタン酸鉄等の無機赤色系顔料;γ-酸化鉄等の無機褐色系顔料;黄酸化鉄、黄土等の無機黄色系顔料;黒酸化鉄、低次酸化チタン等の無機黒色系顔料;マンゴバイオレット、コバルトバイオレット等の無機紫色系顔料;酸化クロム、水酸化クロム、チタン酸コバルト等の無機緑色系顔料;群青、紺青等の無機青色系顔料;酸化チタンコーテッドマイカ、酸化チタンコーテッドオキシ塩化ビスマス、酸化チタンコーテッドタルク、着色酸化チタンコーテッドマイカ、オキシ塩化ビスマス、魚鱗箔等のパール顔料;タルク、セリサイト、マイカ、カオリン、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸、硫酸バリウム、水酸化アルミニウム等の体質顔料;アルミニウムパウダー、カッパーパウダー、金等の金属粉末顔料;表面処理無機及び金属粉末顔料;ジルコニウム、バリウム又はアルミニウムレーキ等の有機顔料;表面処理有機顔料等が好ましいものとして挙げられる。
本発明の組成物は、上記式(1)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ゲル化剤と、水と、脂肪酸塩と、酸性の低分子化合物と、界面活性剤と、粉体、そして所望により多価アルコールなどのその他添加剤とを用い、これらを混合することによって製造され得る。
a)脂質ペプチド型ゲル化剤と、脂肪酸塩と、水とを混合して、プレミックス(水性組成物)を調製する工程、
b)前記工程a)で得られたプレミックスと、酸性の低分子化合物と、界面活性剤とを混合して、混合溶液を調製する工程、
c)前記工程b)で得られた混合溶液と、粉体とを混合して、本発明の組成物を得る工程。
ここで、多価アルコールやその他添加剤は、a)工程において添加してもよいし、b)工程において添加してもよいし、又はc)工程において添加してもよい。
また、こうして得られた本発明の組成物の総質量に対して、水は60質量%以上99.9質量%以下であることが好ましい。
本実施例において用いた脂質ペプチド型化合物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の混合溶液に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。
Pal-GH、添加剤としてステアリン酸、水酸化ナトリウム、1,3‐ブタンジオール及び水を、下記の表1に示す割合にて300mLビーカーに加え、液温80℃、300rpmで20分~90分間加熱撹拌を行った。その後加熱を止め、300rpmで1時間、撹拌放冷を行った後、蒸発分の水を補充しさらに300rpmで1分間撹拌した。その後室温で一晩以上放置を行い、TW‐01Wプレミックスを調製した。
300mLトールビーカーに下記の表2に示す割合にてB相を秤量し、液温80℃、100rpmで撹拌を行った。固形物が溶解したことを目視で確認した後、A相であるTW-01Wプレミックスを添加し、室温付近まで撹拌冷却した。得られた混合溶液(A相+B相)1mLを取り分け、そこへ10%CPC(ヘキサデシルピリジニウムクロリド一水和物,和光純薬工業(株)製)水溶液又は10%リドカイン塩酸塩水溶液を添加し、ゲル形成(ゲルとは、溶液の流動性が失われて、サンプル管を倒置しても溶液が流れ落ちない状態のものをいう)を目視により観察した。10%CPC水溶液又は10%リドカイン塩酸塩水溶液の添加量上限を600μLとし、600μL添加後にもゲル化が見られない場合には「ゲル形成せず」と下記の表2に記載した。また、ゲル形成が確認できた参考例1のゲル調製後のサンプル管の写真を図1に示す。
ステアロイル乳酸ナトリウム:(株)武蔵野化学研究所製
マグビオブライドMG‐T:日油(株)製
12‐ヒドロキシステアリン酸:東京化成工業(株)製
10%CPC水溶液:ヘキサデシルピリジニウムクロリド一水和物(和光純薬工業(株)製)の濃度が10wt%となるように純水に溶解させて調製したものである。
10%リドカイン塩酸塩水溶液:リドカイン塩酸塩(日新製薬)の濃度が10wt%となるように純水に溶解させて調製したものである。
表3に従い各組成物を秤量し、以下に示す手順で組成物を調製した。
TW-01Wプレミックスを80℃に加熱した。他方でA相を80℃に加熱した。加熱撹拌を行っているA相へ加熱したTW-01Wプレミックスを添加した後、撹拌冷却を行った。液温が50℃となったところでB相を添加し、液温が40℃となるまでさらに撹拌冷却を行った。ヒドロキシアパタイトの分散性は組成物調製後にヒドロキシアパタイトが沈澱している場合は×とした。一方で、ヒドロキシアパタイトが分散を維持している場合には○とした。実施例2における、ヒドロキシアパタイトが分散していることを示すサンプル管の写真を図2に示す。
300mLトールビーカーに純水190gを量りとり、そこへ実施例2の組成物10gを添加した。これをNEO SHAKER(アズワン(株)製)を用いて、197rpmで撹拌を2分間行った後、分散性を目視にて確認したところ、ゲルの塊は見られず均一に分散していた(図3は撹拌前のトールビーカーの写真である。図4は撹拌中のトールビーカーの写真である。図5は撹拌後のトールビーカーの写真である。)。
Claims (8)
- 前記脂肪酸塩が酪酸塩、吉草酸塩、カプロン酸塩、エナント酸塩、カプリル酸塩、ペラルゴン酸塩、カプリン酸塩、ラウリン酸塩、ミリスチン酸塩、ペンタデシル酸塩、パルミチン酸塩、パルミトレイン酸塩、マルガリン酸塩、ステアリン酸塩、オレイン酸塩、バクセン酸塩、リノール酸塩、(9,12,15)-リノレン酸塩、(6,9,12)-リノレン酸塩、エレオステアリン酸塩、ツベルクロステアリン酸塩、アラキジン酸塩、アラキドン酸塩、ベヘン酸塩、リグノセリン酸塩、ネルボン酸塩、セロチン酸塩、モンタン酸塩及びメリシン酸塩からなる群から選択される少なくとも一種の脂肪酸塩である、請求項1に記載の組成物。
- 前記界面活性剤が炭素原子数11以上の炭化水素鎖を有するアニオン性またはノニオン性界面活性剤である、請求項1又は請求項2に記載の組成物。
- 前記酸性の低分子化合物が第4級アンモニウム塩及び/又は有機酸の塩酸塩である、請求項1乃至請求項3のいずれか1項に記載の組成物。
- 更に多価アルコールを含有する、請求項1乃至請求項4のいずれか1項に記載の組成物。
- 水中で速やかに拡散する、請求項1乃至請求項5のいずれか1項に記載の組成物。
- 口腔洗浄剤である、請求項1乃至請求項6のいずれか1項に記載の組成物。
- 液状歯磨剤である、請求項1乃至請求項6のいずれか1項に記載の組成物。
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