WO2016195017A1 - 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル及びその用途 - Google Patents
10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル及びその用途 Download PDFInfo
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- WO2016195017A1 WO2016195017A1 PCT/JP2016/066406 JP2016066406W WO2016195017A1 WO 2016195017 A1 WO2016195017 A1 WO 2016195017A1 JP 2016066406 W JP2016066406 W JP 2016066406W WO 2016195017 A1 WO2016195017 A1 WO 2016195017A1
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- cis
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- present
- optical isomer
- octadecenoic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
- A23D9/007—Other edible oils or fats, e.g. shortenings, cooking oils characterised by ingredients other than fatty acid triglycerides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or 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
- A61K8/30—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
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
Definitions
- the present invention relates to an alkyl ester of 10-hydroxy-cis-12-octadecenoic acid (hereinafter sometimes abbreviated as “HYA”), an ester with a divalent alkanol, or an optical isomer thereof.
- HYA 10-hydroxy-cis-12-octadecenoic acid
- the present invention also relates to the use of the ester or its optical isomer as an edible oil and fat, and a composition (food, medicine, cosmetic, feed, etc.) containing the ester or its optical isomer.
- Non-patent Document 1 conjugated fatty acids such as conjugated linoleic acid
- Patent Document 1 ⁇ 3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid
- Patent Document 1 has lipid metabolism improving action, diabetes improving action, etc.
- lipid metabolism improving action has been reported.
- One of the rare fatty acids is a hydroxylated fatty acid having a hydroxyl group in the compound.
- linoleic acid which is abundant in vegetable oils, has been used as a starting material for high efficiency and high selectivity.
- Patent Document 2 A means for manufacturing was found. And while the supply method of various hydroxylated fatty acids is ensured, the research regarding the physiological function is also actively performed.
- HYA 10-hydroxy-cis-12-octadecenoic acid
- Patent Document 3 10-hydroxy-cis-12-octadecenoic acid
- Non-patent document 2 It has been reported that it has an action to suppress inflammation of the intestinal tract
- HYA high-purity
- alkyl esters of HYA it has been reported that methyl 10-hydroxy-cis-12-octadecenoate and ethyl 10-hydroxy-cis-12-octadecenoate were used as intermediates for the production of sebacic acid (Patent Literature). 5) They are not used for any purpose other than the production intermediate. In addition, no alkyl ester of HYA other than methyl 10-hydroxy-cis-12-octadecenoate and ethyl 10-hydroxy-cis-12-octadecenoate has been reported so far.
- An object of the present invention is to provide a novel HYA derivative that has an excellent physiological function of HYA and is easy to ingest and handle.
- the present invention is as follows: [1] 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof (excluding methyl 10-hydroxy-cis-12-octadecenate and ethyl 10-hydroxy-cis-12-octadecenoate). [2] The 10-hydroxy-cis-12-octadecenoic acid alkyl ester or the optical isomer thereof according to the above [1], which is liquid at normal temperature. [3] An edible oil or fat characterized by containing 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof.
- a food or food additive comprising 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof.
- a pharmaceutical composition comprising 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof.
- a preventive or therapeutic agent for a disease selected from the group consisting of inflammation, Crohn's disease, irritable bowel syndrome and inflammatory disease.
- a cosmetic or cosmetic additive comprising 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof.
- a feed or a feed additive comprising 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof.
- the ester or optical isomer thereof according to [9] which is liquid at normal temperature.
- a pharmaceutical composition comprising the ester according to [9] or [10] or an optical isomer thereof.
- esters of 10-hydroxy-cis-12-octadecenoic acid with mono- or divalent alkanols (10-hydroxy-cis-12-octadecenoic acid alkyl esters and alkylene glycols 10-hydroxy-cis-12- Octadecenoic acid esters) and optical isomers thereof (hereinafter, these may be collectively referred to as “compounds of the present invention”).
- the compound of the present invention is a derivative of HYA that is liquid at room temperature, has a good flavor, and is easy to ingest and handle.
- the compound of the present invention after ingestion, hydrolyzes the ester bond in the molecule by lipase or the like in the body and releases HYA, so that it has an excellent physiological function as in the case of ingestion of HYA alone ( It is expected to exert lipid metabolism abnormality improving action, action for enhancing intestinal immunity, action for suppressing intestinal inflammation, and the like. Therefore, the compound of the present invention having the above functions can be used as an edible fat and oil, used as various foods and food additives, and further used in various fields such as pharmaceuticals, cosmetics and feeds. Since it can be used, it is extremely useful in industry.
- acyl (group) means alkanoyl, alkenoyl or aroyl.
- Alkanoyl is formyl, linear or branched alkylcarbonyl, and examples include formyl, acetyl, propanoyl (propionyl), butanoyl (butyryl), isobutanoyl (isobutyryl), pentanoyl, hexanoyl, heptanoyl and the like.
- Alkenoyl is linear or branched alkenylcarbonyl, and examples thereof include propenoyl (acrylyl), butenoyl, oleoyl and the like.
- Aroyl is arylcarbonyl, and examples thereof include benzoyl and naphthoyl.
- alkyl (group) means a linear or branched alkyl group having 1 or more carbon atoms, and is usually C 1-40 alkyl unless there is a limitation on the number of carbon atoms.
- a group preferably a C 1-20 alkyl group, particularly preferably a C 1-6 alkyl group, and most preferably a C 1-3 alkyl group.
- C 1-40 alkyl (group) means a linear or branched alkyl group having 1 to 40 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl.
- C 1-20 alkyl (group) means a linear or branched alkyl group having 1 to 20 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl.
- C 1-6 alkyl (group) means a linear or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl. Sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Can be mentioned.
- C 1-3 alkyl (group) means a linear or branched alkyl group having 1 to 3 carbon atoms, and examples thereof include methyl, ethyl, propyl, isopropyl and the like. .
- alkyl ester in “10-hydroxy-cis-12-octadecenoic acid alkyl ester” or “alkyl ester of fatty acid” means an alcohol having a defined alkyl group (monovalent alkanol), and It means an ester formed with 10-hydroxy-cis-12-octadecenoic acid or a fatty acid.
- the alkyl group constituting the “alkyl ester” may be substituted.
- alkylene glycol mono 10-hydroxy-cis-12-octadecenoic acid ester and “alkylene glycol di 10-hydroxy-cis-12-octadecenoic acid ester” are divalent alkanol (alkanediol) and Monoesters and diesters with 10-hydroxy-cis-12-octadecenoic acid are meant.
- the alkylene glycol constituting the monoester or diester may be substituted.
- alkylene glycol in the above means a divalent linear or branched alkanol (alkanediol).
- the alkylene glycol in the present invention is usually C 1-8 alkylene glycol, preferably C 2-6 alkylene glycol, more preferably C 2-4 alkylene glycol.
- the two hydroxyl groups in such an alkylene glycol may be bonded to any position of the alkylene chain as long as they can form an ester with 10-hydroxy-cis-12-octadecenoic acid.
- C 1-8 alkylene glycol refers to a divalent alkanol having 1 to 8 carbon atoms
- C 2-6 alkylene glycol refers to a divalent alkanol having 2 to 6 carbon atoms
- C 2-4 alkylene glycol refers to a divalent alkanol having 2 to 4 carbon atoms.
- Specific examples of such alkylene glycol include methylene glycol (methanediol), ethylene glycol (ethanediol), 1,2-propylene glycol (1,2-propanediol), 1,3-propylene glycol (1,3-propane).
- Diol 1,3-butylene glycol (1,3-butanediol), 1,2-pentylene glycol (1,2-pentanediol), 1,2-hexylene glycol (1,2-hexanediol),
- Examples include hexylene glycol (2-methyl-2,4-pentanediol), 1,2-octylene glycol (1,2-octanediol), ethylene glycol (ethanediol), 1,2-propylene glycol ( 1,2-propanediol), 1,3-propylene glycol (1 3-propanediol), 1,3-butylene glycol (1,3-butanediol), 1,2-pentylene glycol (1,2-pentanediol), 1,2-hexylene glycol (1,2-hexane) Diol), hexylene glycol (2-methyl-2,4-pentanediol) and the like, ethylene glycol (e
- alkylene (group) is a divalent substituent of a linear or branched alkane having 1 or more carbon atoms, and is usually a C 1-8 alkylene group, preferably C 2- 6 alkylene group, more preferably C 2-4 alkylene group.
- C 1-8 alkylene (group) means a linear or branched alkylene group having 1 to 8 carbon atoms, such as methylene, ethylene, propylene, 1-methylethylene, butylene. 1-methylpropylene, pentylene, 1-propylethylene, hexylene, 1-butylethylene, 1,1,3-trimethylpropylene, heptylene, octylene, 1-hexylethylene and the like.
- C 2-6 alkylene (group) means a linear or branched alkylene group having 2 to 6 carbon atoms, such as ethylene, propylene, 1-methylethylene, butylene, 1 -Methylpropylene, pentylene, 1-propylethylene, hexylene, 1-butylethylene, 1,1,3-trimethylpropylene and the like.
- C 2-4 alkylene (group) means a linear or branched alkylene group having 2 to 4 carbon atoms, such as ethylene, propylene, 1-methylethylene, butylene, 1 -Methylpropylene and the like.
- “optionally substituted” means that it may have one or more substituents, and the “substituent” is not particularly limited, but may be a halogen atom,
- Optionally protected hydroxyl group eg, hydroxyl group, C 1-6 alkoxy group, C 1-7 alkanoyloxy group, C 7-11 aroyloxy group, C 1-6 alkylsulfonyloxy group, C 6-10 arylsulfonyloxy group) Group, hydroperoxy group, etc.
- mercapto group which may be protected (eg, mercapto group, methylthio group, acetylthio group, etc.)
- carboxy group which may be protected (eg, carboxy group, C 1-6 alkoxy- A carbonyl group, etc.)
- an optionally protected amino group eg, amino group, methylamino group, acetylamino group, dimethylamino group, etc.
- acyl group eg, C 1-7
- “optionally protected hydroxyl group”, “optionally protected mercapto group”, “optionally protected carboxy group” or “optionally protected amino group” It means a hydroxyl group, mercapto group, carboxy group, or amino group which may be protected with a “protecting group”.
- a protecting group for example, a protecting group for a hydroxyl group, a mercapto group, a carboxy group, or an amino group described in Protective Groups in Organic Synthesis, published by John Wiley and Sons (1980) can be used.
- Protecting groups such as C 1-6 alkyl group, C 7-14 aralkyl group, C 6-10 aryl group, C 1-7 alkanoyl group, C 7-14 aralkyl-carbonyl group, tri-C 1-6 alkylsilyl group Can be mentioned.
- the above protecting group may be further substituted with a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group or a nitro group.
- the “optionally protected hydroxyl group”, “optionally protected mercapto group”, “optionally protected carboxy group”, or “optionally protected amino group” includes a hydroxyl group, A group in which a group derived from a natural product such as sugar, amino acid, fatty acid, nucleic acid, phosphoric acid, sulfuric acid or the like is bound to a mercapto group, a carboxy group, or an amino group is also included.
- the compound of the present invention contains 10-hydroxy-cis-12-octadecenoic acid alkyl ester or an optical isomer thereof (hereinafter referred to as “the compound (1) of the present invention”). Is).
- the compound of the present invention is a monoester formed from 10-hydroxy-cis-12-octadecenoic acid and a divalent alkanol (“alkylene glycol mono 10-hydroxy-cis- 12-octadecenoic acid ester ”) or an optical isomer thereof (hereinafter sometimes referred to as“ compound (2) of the present invention ”).
- the compound of the present invention is a diester formed from 10-hydroxy-cis-12-octadecenoic acid and a divalent alkanol (“alkylene glycol di10-hydroxy-cis-12- Or an optical isomer thereof (hereinafter sometimes referred to as “compound (3) of the present invention”).
- the compound (1) of the present invention is specifically represented by the following formula (I):
- R 1 represents an optionally substituted alkyl group.
- the compound (1) of the present invention may be an ester formed from one monovalent alkanol and 10-hydroxy-cis-12-octadecenoic acid, or two or more monovalent alkanols, It may be a mixture of esters formed with 10-hydroxy-cis-12-octadecenoic acid.
- R 2 represents an alkylene glycol residue which may be substituted.
- the optionally substituted alkylene glycol residue represented by R 2 is an alkylene glycol residue as defined above.
- the compound (2) of the present invention may be a monoester formed from one kind of divalent alkanol (alkylene glycol) and 10-hydroxy-cis-12-octadecenoic acid, or two or more kinds It may be a mixture of monoesters formed from a divalent alkanol (alkylene glycol) and 10-hydroxy-cis-12-octadecenoic acid.
- the compound (3) of the present invention is specifically represented by the following formula (III):
- X represents an optionally substituted alkylene group.
- the optionally substituted alkylene group represented by X is as defined above.
- the compound (3) of the present invention may be a diester formed from one divalent alkanol (alkylene glycol) and 10-hydroxy-cis-12-octadecenoic acid, or two or more diesters. It may also be a mixture of diesters formed from a divalent alkanol (alkylene glycol) and 10-hydroxy-cis-12-octadecenoic acid.
- any isomers and mixtures thereof are also compounds of the present invention.
- (1) to (3) are included.
- Each can be obtained as an optically pure compound by a known synthesis method, separation method (recrystallization method, separation by high performance liquid chromatography using an optically active column, enzyme method, or the like).
- separation method separation method, separation by high performance liquid chromatography using an optically active column, enzyme method, or the like.
- optical isomers may be used in a mixed state, optically pure compounds obtained by separation from each other may be used alone, or they may be used in combination.
- the compounds (1) to (3) of the present invention are desirably liquid at normal temperature.
- normal temperature means normal temperature (15 ° C. to 25 ° C.) defined by the 16th revised Japanese Pharmacopoeia General Rules and the 17th revised Japanese Pharmacopoeia General Rules.
- the compounds (2) and (3) of the present invention can also be used as foods or food additives.
- compositions administered parenterally It is particularly suitable for use as a product and as a cosmetic or cosmetic additive.
- the production method of the compound of the present invention is not particularly limited.
- HYA or an activated form thereof eg, acid halide, active ester, acid anhydride, etc.
- alkanol monovalent or divalent alkanol
- Esterification method (production method 1), HYA or its activated form eg, acid halide, active ester, acid anhydride, etc.
- fatty acid alkyl ester or alkylene glycol ester hereinafter abbreviated as fatty acid ester
- Transesterification reaction Production Method 2
- preferred ones can be selected in consideration of the stability of the raw material compounds and products, and a plurality of production methods can be combined.
- reaction steps such as protection and deprotection can be appropriately incorporated as necessary.
- HYA used in each of the above production methods can be prepared by the method described in Patent Document 2.
- the alkanol and fatty acid or activated form thereof (eg, acid halide, active ester, acid anhydride, etc.) used in each of the above-mentioned production methods are commercially available, or are known per se from commercially available raw material compounds, or to it. It can be synthesized and used in accordance with a similar method.
- the esterification step of production method 1 can be performed using an enzymatic reaction or a chemical reaction, but it is preferable to use an enzymatic reaction that is simple in reaction operation and mild in reaction conditions.
- the enzyme used for the esterification reaction in Production Method 1 is not particularly limited as long as it can be converted into the compound of the present invention, and examples thereof include lipase and esterase. Among them, lipase is preferable.
- the lipase can be obtained as a commercial product from Novozymes, Amano Enzyme Co., Ltd., Meisho Sangyo Co., Ltd., Sigma-Aldrich Co., etc.
- the alkanol used as the reaction substrate in production method 1 can be used without particular limitation as long as it is a monovalent or divalent alkanol from which the compound of the present invention can be obtained by an esterification reaction with HYA.
- the monovalent alkanol include alkanols having 1 to 40 carbon atoms, among which methanol, ethanol, propanol and the like are preferable.
- the divalent alkanol include alkane diols having 1 to 8 carbon atoms, preferably alkane diols having 2 to 6 carbon atoms, and alkane diols having 2 to 4 carbon atoms such as ethylene glycol, propylene glycol, and butylene glycol. More preferred.
- the water content in the reaction substrate and the solvent is as low as possible so that the compounds (1) to (3) of the present invention which are reaction products are not hydrolyzed.
- the reaction can be carried out in the absence of a solvent or in various non-aqueous solvents (eg, non-polar solvents such as n-heptane, n-hexane, isooctane, etc.), but the reaction without a solvent is more preferred.
- the reaction can be carried out under reduced pressure in order to remove the water from the reaction system, shift the equilibrium of the reaction, promote the esterification reaction, or reduce the water content in the reaction substrate or solvent used. .
- the reaction temperature in production method 1 varies depending on the presence or absence of a solvent, the type of solvent when a solvent is used, the type of enzyme, the state of HYA that is a reaction substrate (type of activated substance, etc.), the type of alkanol, etc. It is 4 ° C to 100 ° C, preferably 20 ° C to 70 ° C, more preferably 30 ° C to 50 ° C.
- the reaction time in production method 1 varies depending on the presence or absence of a solvent, the type of solvent when a solvent is used, the type of enzyme, the state of HYA as a reaction substrate (type of activated substance), the type of alkanol, etc.
- the time is 168 hours, preferably 5 to 48 hours.
- the amount of HYA and alkanol used as reaction substrates in production method 1 depends on the type of alkanol used, but is preferably 10% by weight to 1000% by weight, more preferably 30% by weight to 500% by weight, based on HYA. 50 to 300% by weight is particularly preferred.
- the amount of the enzyme used for HYA used as a reaction substrate in production method 1 is preferably 1% by weight to 100% by weight, more preferably 1% by weight to 50% by weight, and particularly preferably 1% by weight to 20% by weight.
- the enzyme used for the enzyme reaction used in the above production method 1 may be immobilized on various carriers or may be a free type, but the immobilized enzyme is an anhydrous reaction system or a reaction system with little moisture. However, it is more preferable in that it has high activity and can be recovered and used repeatedly. Any of the above enzymes may be purified or may be a crude product. Alternatively, it may be expressed in bacterial cells such as Escherichia coli, and the bacterial cells themselves may be used, or a culture solution of the bacterial cells may be used.
- the present invention provides an edible oil and fat containing the compound of the present invention (hereinafter also referred to as “edible oil and fat of the present invention” in the present specification). That is, the compound of the present invention can be used as an edible oil or fat alone or in combination with other edible oils and fats.
- the content of the compound of the present invention in the edible fat / oil of the present invention is not particularly limited, but is usually 5% by weight or more, preferably 20% by weight or more, and preferably 50% by weight or more, based on the total amount of edible fat / oil. More preferably, it is particularly preferred to be used alone as an edible fat or oil in that excellent flavor and physiological function can be obtained.
- the edible oil / fat of the present invention can contain, for example, general components (food additives, etc.) used in edible oil / fat, as long as the characteristics of the present invention are not impaired.
- general components food additives, etc.
- these components include emulsifiers, oxidation / deterioration inhibitors, antifoaming agents, and crystal modifiers.
- Examples of the emulsifier include glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, polyglycerin condensed ricinoleic acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and organic acid monoglyceride. It is done.
- Examples of the oxidation / degradation inhibitor include tocopherols, flavone derivatives, gallic acid derivatives, catechins and esters thereof, lignans (eg, sesamin), fucic acid, sesamol, terpenes, and the like.
- Examples of the antifoaming agent include silicone oil.
- crystal modifier examples include triacylglycerol, diacylglycerol, mono fatty acid glyceryl, hepta fatty acid decaglyceryl, deca fatty acid decaglyceryl, waxes, sterol esters and the like.
- Spices and coloring agents can also be added. Examples of spices include capsaicin, anethole, eugenol, cineol, gingerone and the like. Examples of the colorant include carotene and astaxanthin.
- the edible fats and oils of the present invention include various nutrients (sugars, proteins, etc.), various vitamins (vitamin A, vitamin B 1 , vitamin B 2 , vitamin B 6 , vitamin C, vitamin D, vitamins as necessary. E, vitamin K, etc.) and various minerals (magnesium, zinc, iron, sodium, potassium, selenium, etc.) can also be contained.
- the present invention provides a food or food additive (hereinafter, also referred to as “the food or food additive of the present invention”) containing the compound of the present invention.
- the food or food additive of the present invention is not particularly limited as long as it can be taken orally, such as a solution, a suspension, an emulsion, a gel, a powder, and a solid molded product.
- the food or food additive of the present invention include supplements (powder, granules, soft capsules, hard capsules, tablets, chewable tablets, quick-disintegrating tablets, syrups, liquids, etc.), beverages (carbonated beverages, lactic acid beverages, sports beverages) , Fruit juice beverages, vegetable beverages, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, nutritional beverages, alcoholic beverages, etc.), confectionery (gummy, jelly, gum, chocolate, cookies, candy, caramel, Japanese confectionery, snack confectionery, etc.
- Instant foods instant noodles, retort foods, canned foods, microwave foods, instant soups and miso soups, freeze-dried foods, etc.
- fat and oil foods mayonnaise, dressing, butter, cream, margarine, etc.
- flour products bread, Pasta, noodles, cake mix, bread crumbs, etc.
- seasonings varietyce, tomato processed seasonings, flavor seasonings
- Cooking mix, soup, etc. such as processed livestock products (meat ham, sausage, etc.) and the like.
- the content of the compound of the present invention in the food or food additive of the present invention is 5 to 90% by weight, preferably 10 to 80% by weight, based on the total amount of the food or food additive. More preferably, it is 20% by weight to 70% by weight.
- the daily intake of the food or food additive of the present invention depends on the age of the subject to be ingested, the symptoms and conditions expected to be improved by the intake, the severity thereof, the dosage form of the food, etc. Although appropriately set, it is preferable to set the intake amount of the compound of the present invention to be approximately the same as the daily dose described later.
- the food or food additive of the present invention includes various nutrients (sugar, protein, etc.) and various vitamins (vitamin A, vitamin B 1 , vitamin B 2 , vitamin B 6 , vitamin C, vitamin D, as necessary. Vitamin E, vitamin K, etc.), various minerals (magnesium, zinc, iron, sodium, potassium, selenium, etc.), dietary fiber, foods with reported physiological functions (royal jelly, propolis, agarics, etc.) be able to.
- the food or food composition of the present invention contains general food additives, for example, emulsifiers (glycerin fatty acid esters, sucrose fatty acid esters, etc.), thickening stabilizers (pectin, sodium carboxymethyl cellulose, etc.) as necessary.
- Antioxidants mixed vitamin E, sodium erythorbate, etc.
- preservatives sodium benzoate, sorbic acid, etc.
- brighteners shellac, beeswax, etc.
- sweeteners xylitol, aspartame, etc.
- acidulants quenched
- Acid malic acid, etc.
- bittering agents caffeine, naringin, etc.
- seasonings sodium L-glutamate, disodium 5'-inosinate, etc.
- coloring agents Kuchinashi yellow, red No. 2, etc.
- flavors Orange flavor, vanillin, etc.
- manufacturing agents birine, binder, etc. and the like can be added.
- the food or food additive of the present invention is prepared by a general production method by adding the above-mentioned various nutrients, various vitamins, etc., and general food additives, if necessary, to the compound of the present invention. can do.
- the edible fats and oils and foods or food additives of the present invention described above include health foods, functional foods, health functional foods (for example, foods for specific health, functional indication foods, etc.), special purpose foods (for example, Foods for sick people, etc.), edible fats and oils with a disease risk reduction label, and foods etc. are also included.
- the “disease risk reduction display” includes, for example, an indication that the disease can be improved, suppressed, and / or prevented by HYA.
- the edible oil / fat, food or food additive of the present invention is capable of improving the symptoms by HYA, for example, obesity, diabetes, lipid metabolism abnormality, hyperlipidemia, fatty liver, inflammatory bowel disease (ulcerative colon) Inflammation, Crohn's disease, pseudomembranous enteritis, etc.), ulcers, irritable bowel syndrome, and various other inflammatory diseases (eg gout, arthritis, polyneuritis, polyradiculitis, hepatitis, bronchitis, pneumonia , Nephritis, cystitis, periodontal disease, dermatitis, atopic dermatitis, etc.) provided as an edible oil, food or food additive with a label indicating that it is intended to improve and / or prevent Can do.
- HYA for example, obesity, diabetes, lipid metabolism abnormality, hyperlipidemia, fatty liver, inflammatory bowel disease (ulcerative colon) Inflammation, Crohn's disease, pseudomembranous enteritis, etc.), ulcers, irritable
- the present invention provides a pharmaceutical composition (hereinafter, also referred to as “the pharmaceutical composition of the present invention”) containing the compound of the present invention.
- the pharmaceutical composition of the present invention is a disease that can improve symptoms for animals by HYA, such as obesity, diabetes, dyslipidemia, hyperlipidemia, fatty liver, inflammatory bowel disease (ulcerative colitis, clone Disease, pseudomembranous enteritis etc.), ulcers, irritable bowel syndrome, and various other inflammatory diseases (eg gout, arthritis, polyneuritis, polyradiculitis, hepatitis, bronchitis, pneumonia, nephritis, Cystitis, periodontal disease, dermatitis, atopic dermatitis, etc.) can be used as a prophylactic agent or a therapeutic agent for treatment, improvement, or suppression.
- the “animal” include humans, mammals such as dogs, cats, rabbits, hamsters, rats, mice, cows, pigs, sheep, horses, donkey
- the pharmaceutical composition of the present invention is not particularly limited, and examples thereof include powders, granules, pills, soft capsules, hard capsules, tablets, chewable tablets, quick-disintegrating tablets, syrups, solutions, suspensions, and emulsions.
- Oral preparations in various dosage forms can be provided as parenteral preparations such as suppositories, ointments, creams, gels, patches, inhalants, injections and the like.
- a general formulation means for example, the 16th revised Japanese Pharmacopoeia Formulation General Rules [2] Formulation Articles, Tenth It can be manufactured according to the methods described in the Seventh Revised Japanese Pharmacopoeia General Formulation [3] Formulations, etc.
- the additive that can be used for formulation is not particularly limited.
- animal and vegetable oils such as soybean oil, safflower oil, olive oil, germ oil, sunflower oil, beef tallow, sardine oil, and the like
- Polyhydric alcohols such as polyethylene glycol, propylene glycol, glycerin, sorbitol
- surfactants such as sorbitan fatty acid ester, sucrose fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester
- purified water sterilized purified water, water for injection, physiological saline Solution, solvents such as ethanol, isopropanol, etc .
- excipients such as lactose, starch, crystalline cellulose, D-mannitol, soybean lecithin, gum arabic, sorbitol solution, chickenpox; pregelatinized starch, carboxymethylcellulose, hydroxypropylcellulose, shellac, etc.
- Binders Binders; disintegrants such as crospovidone, povidone, dextrin; lubricants such as magnesium silicate, aluminum stearate, talc; sweeteners such as aspartame, liquorice extract, sodium saccharin; yellow iron oxide, brown iron oxide, black oxide Coloring agents such as iron, edible blue No. 1 and edible red No. 2; pH adjusting agents such as hydrochloric acid, citric acid, sodium citrate, potassium hydroxide, sodium hydroxide; and flavors such as bitter essence.
- disintegrants such as crospovidone, povidone, dextrin
- lubricants such as magnesium silicate, aluminum stearate, talc
- sweeteners such as aspartame, liquorice extract, sodium saccharin
- yellow iron oxide, brown iron oxide, black oxide Coloring agents such as iron, edible blue No. 1 and edible red No. 2
- pH adjusting agents such as hydrochloric acid, citric acid, sodium citrate, potassium hydroxide, sodium hydroxide
- a therapeutic drug for the above-described diseases that can be improved or prevented by the pharmaceutical composition of the present invention may be used in combination with the compound of the present invention within a range not impairing the effects of the present invention.
- examples of the drug that can be used in combination in the pharmaceutical composition of the present invention include, for example, sulfonylurea drugs (tolbutamide, glyclopyramide, glybazole, glimepiride, etc.), biguanide drugs (hydrochloric acid) Metformin, etc.), ⁇ -glucosidase inhibitors (voglibose, acarbose, etc.), thiazolidine derivatives (pioglitazone hydrochloride, etc.) and other antidiabetic drugs; statins (pravastatin sodium, simvastatin, pitavastatin calcium, etc.), anion exchange resins
- the composition of the present invention is a parenteral preparation such as an injection
- the composition is not particularly limited.
- the composition is intravenous, intraperitoneal, intramuscular, subcutaneous, transdermal, intraarticular, slippery. It is preferable to administer into the sac, periosteum, sublingual, intraoral, etc., and particularly preferably intravenously or intraperitoneally.
- Intravenous administration may be either drip administration or bolus administration.
- the content of the compound of the present invention in the pharmaceutical composition of the present invention is 5% to 100% by weight, preferably 10% to 90% by weight, more preferably based on the total amount of the pharmaceutical composition of the present invention. Preferably, it is 20 to 80% by weight.
- the dosage of the pharmaceutical composition of the present invention can be appropriately determined according to the type of animal to be administered, age and weight, symptoms and severity, the dosage form of the pharmaceutical composition, the method of administration, the type of concomitant drug, etc. it can.
- the total amount in terms of HYA as an active ingredient is 0.02 mg / kg body weight to 100 mg / kg body weight per day for adults, preferably 0.2 mg / kg body weight In the range of ⁇ 50 mg / kg body weight, and when administered parenterally to humans, 0.002 mg / kg body weight to 50 mg / kg body weight, preferably 0.02 mg / kg body weight to 50 mg / kg It can be administered in the range of kg body weight.
- the above amount can be administered once a day or divided into several times (2 to 5 times).
- the administration period of the pharmaceutical composition of the present invention can be appropriately determined according to the condition, symptoms and severity of the animal to be administered, and is usually 1 day to 90 days, preferably 7 days to 30 days.
- the present invention provides a cosmetic or cosmetic additive (hereinafter, also referred to as “the cosmetic or cosmetic additive of the present invention”) containing the compound of the present invention.
- the cosmetic of the present invention can be prepared according to the above-described method for producing a pharmaceutical composition by adding various additives to the compound of the present invention as necessary.
- Cosmetics of the present invention are cosmetics for skin such as cream, gel, milky lotion, cosmetic liquid, lotion, microemulsion essence and pack; makeup cosmetics such as foundation, lipstick, eye shadow, cheek color; cleansing oil, cleansing Cosmetics for cleaning such as cream; cosmetics for hair such as shampoos and conditioners; cosmetics of various shapes such as bathing agents.
- the cosmetic composition of the present invention includes an active ingredient such as an anti-wrinkle / anti-aging agent, an anti-inflammatory agent, an anti-rough skin agent, a cell activation / wound healing agent, a whitening agent, and an oil agent within the range that does not impair the characteristics of the present invention.
- an active ingredient such as an anti-wrinkle / anti-aging agent, an anti-inflammatory agent, an anti-rough skin agent, a cell activation / wound healing agent, a whitening agent, and an oil agent within the range that does not impair the characteristics of the present invention.
- the cosmetic additive of the present invention is added to the compound of the present invention, if necessary, the above-mentioned oil agent, surfactant, solvent, thickener, pigment, etc., according to the method for producing the above pharmaceutical composition, It can be in the form of oil, suspension, milk, paste, powder, granule or the like.
- the content of the compound of the present invention in the cosmetic or cosmetic additive of the present invention is 5 to 70% by weight, preferably 10 to 60% by weight, based on the total amount of the cosmetic or the like of the present invention. More preferably, it is 20 to 50% by weight.
- the present invention provides a feed or feed additive containing the compound of the present invention (hereinafter sometimes referred to as “the feed or feed additive of the present invention”).
- the feed or feed additive of the present invention can be in the form of an oil, suspension, emulsion, gel, powder, granule, tablet or the like.
- Examples of the feed or feed additive of the present invention include pet food, livestock or aquaculture feed additive, and the like.
- the feed or feed additive of the present invention can be prepared according to a usual method by mixing the compound of the present invention with a feed shaping substance, a diluent substance and the like.
- the excipient and diluent for feed can be used without particular limitation as long as the characteristics of the present invention are not impaired.
- polysaccharides such as gum arabic, carrageenan, agar, xanthan gum, chitosan, cellulose, locust bean gum; glucose Monosaccharides or disaccharides such as lactose, maltose, and sucrose; sugar alcohols such as glycerin, sorbitol, and D-mannitol; proteins such as albumin, casein, gluten, and gelatin; grain flours such as kina flour, wheat flour, soybean flour, and corn flour ; Yeasts such as torula yeast, baker's yeast, beer yeast; oils and fats such as hardened oil, vegetable oils and animal fats; clay minerals such as kaolin, zeolite, talc, vermiculite and bentonite; diatomaceous earth, hydrous silicon dioxide, silicic acid, Light anhydrous silicic acid, anhydrous silicic acid, calcium silicate, magnesium silicate Silicic acid or a salt thereof; and the wax such as carnauba
- an amino acid such as glycine, DL-alanine, sodium L-glutamate or a salt thereof; L-ascorbic acid, ergocalciferol, Vitamins such as thiamine hydrochloride, cholecalciferol, vitamin A powder, vitamin D powder, riboflavin; minerals such as potassium chloride, iron citrate and calcium gluconate; additives for supplementing nutrients such as pigments such as astaxanthin and canthaxanthin Can be added.
- an amino acid such as glycine, DL-alanine, sodium L-glutamate or a salt thereof
- L-ascorbic acid such as thiamine hydrochloride, cholecalciferol, vitamin A powder, vitamin D powder, riboflavin
- minerals such as potassium chloride, iron citrate and calcium gluconate
- additives for supplementing nutrients such as pigments such as astaxanthin and canthaxanthin Can be added.
- the content of the compound of the present invention in the feed or feed additive of the present invention is 1 to 70% by weight, preferably 3 to 50% by weight, based on the total amount of the feed or the like of the present invention. More preferably, it is 5 to 30% by weight.
- the compounds (1) to (3) of the present invention were produced according to the above production method 1.
- the alkanol ethanol, propanol and ethylene glycol
- commercially available products manufactured by Wako Pure Chemical Industries, Ltd.
- HYA is prepared by the method described in Patent Document 2. It was.
- Other raw material compounds and reagents can be produced by using commercially available products as they are, or by methods known per se, or methods analogous thereto.
- Example 1 Compound (1) of the present invention: ethyl 10-hydroxy-cis-12-octadecenoate In a 100 mL reaction vessel (medium bottle), HYA (5 g), transesterase (lipase) (Novozymes) , Lipozyme RMIM, 1 g) and ethanol (5 g) were added, and the gas phase portion of the reaction system was replaced with nitrogen gas, followed by stirring at 40 ° C. for 28 hours. The transesterification enzyme was removed by filtration using filter paper, and then concentrated to obtain ethyl 10-hydroxy-cis-12-octadecenate (5.5 g; yield 100%).
- Example 2 Compound (1) of the present invention: propyl 10-hydroxy-cis-12-octadecenoate In a 100 mL reaction vessel (medium bottle), HYA (0.5 g), transesterase (lipase) (Novozymes) ), Lipozyme RMIM, 0.1 g) and propanol (0.5 g) were added, and the gas phase portion of the reaction system was replaced with nitrogen gas, followed by stirring at 40 ° C. for 14.5 hours. The transesterification enzyme was removed by filtration using filter paper, and then concentrated to obtain propyl 10-hydroxy-cis-12-octadecenoate (0.5 g; yield 88%).
- Example 3 Compound (2) of the present invention: ethylene glycol mono 10-hydroxy-cis-12-octadecenoic acid ester and Compound (3) of the present invention: ethylene glycol di-10-hydroxy-cis-12-octadecenoic acid Ester
- HYA 0.5 g
- transesterification enzyme lipase
- ethylene glycol 260.7 mg
- the gas phase portion of the reaction system was replaced with nitrogen gas, and then stirred at 40 ° C. for 72 hours.
- the compounds of Examples 1 and 2 were liquid at room temperature, and HYA of the comparative example was solid at room temperature. Therefore, it has been found that the compound of the present invention in which 10-hydroxy-cis-12-octadecenoic acid (HYA) is an ethyl ester or propyl ester exists in a liquid state at room temperature.
- HYA 10-hydroxy-cis-12-octadecenoic acid
- Example 2 For the compound of Example 1 and the flavor of HYA of the Comparative Example, sensory evaluation (hereinafter referred to as taste test) was performed by panelists (10 persons). After taking a 5 mg sample (the sample name was concealed from the paneler at the time of the test), the panelist evaluated the five tastes (umami, bitterness, sourness, saltiness, sweetness), irritation and oily odor, and comprehensive evaluation. Went. Each evaluation was evaluated in five stages as follows, and an average value of evaluation scores of 10 panelists was calculated.
- the HYA of the comparative example showed strong irritation and moderate oily odor
- the compound of Example 1 of the present invention was compared with the comparative example.
- the evaluation of umami and sweetness was high, the irritation was remarkably reduced, and the oily odor was slightly reduced. Furthermore, the overall evaluation was also high.
- the compound of the present invention can exist in liquid form at room temperature due to a decrease in melting point.
- the compound of Example 1 did not have irritation and exhibited a strong umami taste.
- the compound of the present invention was found to be liquid at room temperature, good in flavor and easy to ingest and handle.
- the compound of the present invention hydrolyzes the ester bond by lipase etc. in the body after ingestion and releases HYA, it has an excellent physiological function (lipid metabolism) as in the case of ingestion of HYA itself. It is expected to exert abnormal ameliorating action, intestinal immunity enhancing action, intestinal inflammation suppressing action, etc., so it can be used as an edible oil and fat, making use of the above functions, and as various foods and food additives
- it is extremely useful industrially in that it can be used in various fields such as pharmaceuticals, cosmetics, and feeds.
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Abstract
Description
[1]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体(但し、10-ヒドロキシ-シス-12-オクタデセン酸メチル及び10-ヒドロキシ-シス-12-オクタデセン酸エチルを除く)。
[2]常温で液体である、上記[1]に記載の10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体。
[3]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、食用油脂。
[4]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、食品又は食品添加物。
[5]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、医薬組成物。
[6]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、肥満、糖尿病、脂質代謝異常、高脂血症、脂肪肝、潰瘍、潰瘍性大腸炎、クローン病、過敏性腸症候群及び炎症性疾患からなる群から選択される疾患の予防又は治療剤。
[7]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、化粧料又は化粧料添加物。
[8]10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、飼料又は飼料添加物。
[9]10-ヒドロキシ-シス-12-オクタデセン酸と二価アルカノールとのエステル又はその光学異性体。
[10]常温で液体である、[9]に記載のエステル又はその光学異性体。
[11][9]又は[10]に記載のエステル又はその光学異性体を含有する、食品又は食品添加物。
[12][9]又は[10]に記載のエステル又はその光学異性体を含有する、医薬組成物。
[13][9]又は[10]に記載のエステル又はその光学異性体を含有する、化粧料又は化粧料添加物。
また、本発明の化合物は、摂取後に、体内でリパーゼ等により分子内のエステル結合が加水分解され、HYAを遊離することから、HYAを単独で摂取した場合と同様に、優れた生理学的機能(脂質代謝異常改善作用、腸管免疫力を高める作用、腸管の炎症の抑制作用等)を発揮することが期待される。
従って、上記機能を有する本発明の化合物は、食用油脂としての利用が可能であり、また、各種食品及び食品添加物としての利用、更には、医薬品、化粧料、飼料等の様々な分野での利用が可能であることから、産業上極めて有用である。
アルカノイルとは、ホルミル、直鎖又は分岐鎖アルキルカルボニルであり、例えば、ホルミル、アセチル、プロパノイル(プロピオニル)、ブタノイル(ブチリル)、イソブタノイル(イソブチリル)、ペンタノイル、ヘキサノイル、ヘプタノイル等が挙げられる。
アルケノイルとは、直鎖又は分岐鎖アルケニルカルボニルであり、例えば、プロペノイル(アクリリル)、ブテノイル、オレオイル等が挙げられる。
アロイルとは、アリールカルボニルであり、例えば、ベンゾイル、ナフトイル等が挙げられる。
ここで、「C1-8アルキレングリコール」とは、炭素数1~8の二価アルカノールをいい、「C2-6アルキレングリコール」とは、炭素数2~6の二価アルカノールをいい、「C2-4アルキレングリコール」とは、炭素数2~4の二価アルカノールをいう。
かかるアルキレングリコールの具体例としては、メチレングリコール(メタンジオール)、エチレングリコール(エタンジオール)、1,2-プロピレングリコール(1,2-プロパンジオール)、1,3-プロピレングリコール(1,3-プロパンジオール)、1,3-ブチレングリコール(1,3-ブタンジオール)、1,2-ペンチレングリコール(1,2-ペンタンジオール)、1,2-ヘキシレングリコール(1,2-ヘキサンジオール)、ヘキシレングリコール(2-メチル-2,4-ペンタンジオール)、1,2-オクチレングリコール(1,2-オクタンジオール)等が挙げられ、エチレングリコール(エタンジオール)、1,2-プロピレングリコール(1,2-プロパンジオール)、1,3-プロピレングリコール(1,3-プロパンジオール)、1,3-ブチレングリコール(1,3-ブタンジオール)、1,2-ペンチレングリコール(1,2-ペンタンジオール)、1,2-ヘキシレングリコール(1,2-ヘキサンジオール)、ヘキシレングリコール(2-メチル-2,4-ペンタンジオール)等が好ましく、エチレングリコール(エタンジオール)、1,2-プロピレングリコール(1,2-プロパンジオール)、1,3-プロピレングリコール(1,3-プロパンジオール)、1,3-ブチレングリコール(1,3-ブタンジオール)等がより好ましい。
また、本発明の別の態様として、本発明の化合物は、10-ヒドロキシ-シス-12-オクタデセン酸と、二価のアルカノールとから形成されるモノエステル(「アルキレングリコールモノ10-ヒドロキシ-シス-12-オクタデセン酸エステル」ともいう)又はその光学異性体(以下、本明細書にて「本発明の化合物(2)」ということがある)である。
本発明のさらに別の態様として、本発明の化合物は、10-ヒドロキシ-シス-12-オクタデセン酸と、二価のアルカノールとから形成されるジエステル(「アルキレングリコールジ10-ヒドロキシ-シス-12-オクタデセン酸エステル」ともいう)又はその光学異性体(以下、本明細書にて「本発明の化合物(3)」ということがある)である。
で表される10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体である。
で表されるアルキレングリコールモノ10-ヒドロキシ-シス-12-オクタデセン酸エステル又はその光学異性体である。
式(II)中、R2で示される置換されていてもよいアルキレングリコールの残基は、上記に定義したアルキレングリコールの残基である。
で表されるアルキレングリコールジ10-ヒドロキシ-シス-12-オクタデセン酸エステル又はその光学異性体である。
式(III)中、Xで示される置換されていてもよいアルキレン基については、上記にて定義した通りである。
なお、本発明の化合物のうち、本発明の化合物(2)及び(3)は、食品又は食品添加物としても利用することができるが、後述する医薬組成物のうち、非経口投与される組成物としての利用、及び、化粧料又は化粧料添加物としての利用に特に適する。
リパーゼは、ノボザイムズ(Novozymes)社、天野エンザイム株式会社、名糖産業株式会社、シグマ-アルドリッチ社等から市販品として入手することができる。
一価のアルカノールとしては、炭素数1~40のアルカノールが挙げられるが、中でも、メタノール、エタノール、プロパノール等が好ましい。
二価のアルカノールとしては、炭素数1~8のアルカンジオールが挙げられるが、炭素数2~6のアルカンジオールが好ましく、炭素数2~4のアルカンジオール、例えばエチレングリコール、プロピレングリコール、ブチレングリコールがより好ましい。
すなわち、本発明の化合物は、単独で、又は他の食用油脂に配合して食用油脂とすることができる。本発明の食用油脂における本発明の化合物の含有量は、特に限定されないが、食用油脂全量当たり通常5重量%以上であり、20重量%以上とすることが好ましく、50重量%以上とすることがより好ましく、優れた風味及び生理学的機能が得られるという点では、単独で食用油脂として使用することが特に好ましい。
酸化・劣化防止剤としては、例えば、トコフェロール類、フラボン誘導体、没食子酸誘導体、カテキン及びそのエステル、リグナン類(例えばセサミンなど)、フキ酸、セサモール、テルペン類等が挙げられる。
消泡剤としては、例えば、シリコーン油等が挙げられる。
結晶調整剤としては、例えば、トリアシルグリセロール、ジアシルグルセロール、モノ脂肪酸グリセリル、ヘプタ脂肪酸デカグリセリル、デカ脂肪酸デカグリセリル、ワックス類、ステロールエステル類等が挙げられる。
また、香辛料や着色剤等も添加することができる。香辛料としては、例えば、カプサイシン、アネトール、オイゲノール、シネオール、ジンゲロン等が挙げられる。着色剤としては、例えば、カロテン、アスタキサンチン等が挙げられる。
本発明の食品又は食品添加物は、溶液、懸濁物、乳化物、ゲル、粉末、固体成形物等、経口摂取可能な形態であればよく、特に限定されるものではない。
本発明の食品又は食品添加物の具体例としては、サプリメント(散剤、顆粒剤、ソフトカプセル、ハードカプセル、錠剤、チュアブル錠、速崩錠、シロップ、液剤等)、飲料(炭酸飲料、乳酸飲料、スポーツ飲料、果汁飲料、野菜飲料、豆乳飲料、コーヒー飲料、茶飲料、粉末飲料、濃縮飲料、栄養飲料、アルコール飲料等)、菓子(グミ、ゼリー、ガム、チョコレート、クッキー、キャンデー、キャラメル、和菓子、スナック菓子等)、即席食品類(即席麺、レトルト食品、缶詰、電子レンジ食品、即席スープ・みそ汁類、フリーズドライ食品等)、油脂食品(マヨネーズ、ドレッシング、バター、クリーム、マーガリン等)、小麦粉製品(パン、パスタ、麺、ケーキミックス、パン粉等)、調味料(ソース、トマト加工調味料、風味調味料、調理ミックス、つゆ類等)、畜産加工品(畜肉ハム・ソーセージ等)等が挙げられる。
本発明の食品又は食品添加物の1日あたりの摂取量は、摂取させる対象者の年齢、摂取により改善等が期待される症状や状態及びその重篤度、食品等の剤形等に応じて適宜設定されるが、本発明の化合物の摂取量が後述する1日あたりの投与量と同程度となるように設定されることが好ましい。
また、本発明の食品又は食品組成物には、必要に応じて一般的な食品用添加剤、例えば乳化剤(グリセリン脂肪酸エステル、ショ糖脂肪酸エステル等)、増粘安定剤(ペクチン、カルボキシメチルセルロースナトリウム等)、酸化防止剤(混合ビタミンE、エリソルビン酸ナトリウム等)、保存料(安息香酸ナトリウム、ソルビン酸等)、光沢剤(セラック、ミツロウ等)、甘味料(キシリトール、アスパルテーム等)、酸味料(クエン酸、リンゴ酸等)、苦味料(カフェイン、ナリンジン等)、調味料(L-グルタミン酸ナトリウム、5’-イノシン酸二ナトリウム等)、着色料(クチナシ黄色素、赤色2号等)、香料(オレンジ香料、バニリン等)、製造用剤(かん水、結着剤等)等を添加することができる。
ここで、「疾病リスク低減表示」としては、例えば、HYAにより症状を改善し得る疾患を治療、改善、抑制、及び/又は予防するためのものである旨の表示が挙げられる。従って、本発明の食用油脂、食品又は食品添加物は、HYAにより症状を改善し得る疾患、例えば、肥満、糖尿病、脂質代謝異常、高脂血症、脂肪肝、炎症性腸疾患(潰瘍性大腸炎、クローン病、偽膜性腸炎等)、潰瘍、過敏性腸症候群、及びその他の種々の炎症性疾患(例えば、痛風、関節炎、多発性神経炎、多発性神経根炎、肝炎、気管支炎、肺炎、腎炎、膀胱炎、歯周病、皮膚炎、アトピー性皮膚炎等)を改善、及び/又は予防するためのものである旨の表示を付した食用油脂、食品又は食品添加物として提供することができる。
本発明の医薬組成物は、動物に対し、HYAにより症状を改善し得る疾患、例えば、肥満、糖尿病、脂質代謝異常、高脂血症、脂肪肝、炎症性腸疾患(潰瘍性大腸炎、クローン病、偽膜性腸炎等)、潰瘍、過敏性腸症候群、及びその他の種々の炎症性疾患(例えば、痛風、関節炎、多発性神経炎、多発性神経根炎、肝炎、気管支炎、肺炎、腎炎、膀胱炎、歯周病、皮膚炎、アトピー性皮膚炎等)を予防するための予防剤、又は治療、改善、抑制するための治療剤として用いることができる。
ここで、「動物」としては、ヒトをはじめ、イヌ、ネコ、ウサギ、ハムスター、ラット、マウス、ウシ、ブタ、ヒツジ、ウマ、ロバ、ラクダ等の哺乳動物が挙げられる。
本発明の医薬組成物は、本発明の化合物に、必要に応じて各種添加剤を加え、一般的な製剤化手段、例えば第十六改正日本薬局方製剤総則[2]製剤各条、第十七改正日本薬局方製剤総則[3]製剤各条等に記載された方法等に従って、製造することができる。
なお、液体製剤とする場合は、用時に水又は他の適切な溶媒に溶解又は懸濁して用いる固形の製剤としてもよい。また、錠剤や顆粒剤には、周知の方法でコーティングを施してもよい。
本発明の医薬組成物において併用し得る薬物(以下、本明細書において「併用薬物」ともいう)としては、例えば、スルホニル尿素薬(トルブタミド、グリクロピラミド、グリブゾール、グリメピリド等)、ビグアナイド薬(塩酸メトホルミン等)、α-グルコシダーゼ阻害薬(ボグリボース、アカルボース等)、チアゾリジン誘導体(塩酸ピオグリタゾン等)等の糖尿病治療薬;スタチン類(プラバスタチンナトリウム、シンバスタチン、ピタバスタチンカルシウム等)、陰イオン交換樹脂(コレスチラミン、コレスチミド等)、フィブラート系薬(クロフィブラート、クリノフィブラート等)、ニコチン酸系薬(ニコチン酸トコフェロール、ニコモール等)等の高脂血症治療薬;サリチル酸製剤(メサラジン等)、持続性サルファ薬(サラゾスルファピリジン等)、副腎皮質ステロイド(ベタメタゾン、プレドニゾロン等)、分子標的治療薬(インフリキシマブ、アダリムマブ等)、免疫抑制剤(アザチオプリン等)等の炎症性腸疾患(クローン病、潰瘍性大腸炎、偽膜性腸炎等)治療薬;抗コリン薬(塩酸ピペタナート、臭化メペンゾラート等)、消化管運動調節薬(トリメブチン等)、合成高分子化合物(ポリカルボフィルカルシウム等)、乳酸菌製剤等の過敏性腸症候群治療薬;痛風発作予防薬(コルヒチン等)、尿酸排泄促進薬(プロベネシド、ブコローム、ベンズブロマロン等)、尿酸生成抑制薬(アロプリノール等)等の痛風治療薬;非ステロイド抗炎症薬(メフェナム酸、ケトプロフェン、ジクロフェナクナトリウム等)、生物活性薬(シクロスポリン等)等の関節炎、神経炎治療薬;インターフェロン製剤(インターフェロンβ、インターフェロンα-2a等)、抗肝炎ウイルス薬(リバビリン、ラミブジン等)、肝機能改善薬(グリチルリチン製剤、グルクロン酸、チオプロニン等)等の肝炎治療薬;β-刺激薬(塩酸エフェドリン、dl-塩酸メチルエフェドリン、塩酸トリメトキノール等)、テオフィリン薬(ジプロフィリン、アミノフィリン等)、抗コリン薬(臭化チオトロピウム水和物等)等の気管支炎治療薬;マクロライド系抗菌薬(クラリスロマイシン、アジスロマイシン等)、ニューキノロン系抗菌薬(レボフロキサシン、ガレノキサシン等)等の肺炎治療薬;アンジオテンシン変換酵素阻害薬(マレイン酸エナラプリル、塩酸デラプリル等)、アンジオテンシンII受容体拮抗薬(ロサルタンカリウム、カンデサルタンシレキセチル等)等の腎炎治療薬;ニューキノロン系抗菌薬(オフロキサシン、レボフロキサシン、ノルフロキサシン等)、ペニシリン系抗菌薬(アモキシシリン、アンピシリン、クロキサシリン等)、セフェム系抗菌薬(塩酸セフカペンピボキシル、塩酸セフォチアムヘキセチル等)、漢方薬(八味地黄丸、猪苓湯等)等の膀胱炎治療薬;セフェム系抗菌薬(セファレキシン等)、殺菌剤(塩化ベンゼトニウム、塩酸クロルヘキシジン等)等の歯周病治療薬;非ステロイド抗炎症薬(ブフェキサマク、ウフェナマート等)、鎮痒薬(クロタミトン等)等の皮膚炎、アトピー性皮膚炎治療薬;免疫調整薬(タクロリムス水和物等)等のアトピー性皮膚炎治療薬等が挙げられる。
また、本発明の医薬組成物の投与期間は、投与する動物の状態、症状および重篤度等に応じて、適宜決定することができ、通常1日間~90日間であり、好ましくは7日間~30日間である。
本発明の化粧料は、本発明の化合物に、必要に応じて各種添加剤を加え、上記した医薬組成物の製造方法に準じて調製することができる。
本発明の化粧料は、クリーム、ゲル、乳液、美容液、ローション、マイクロエマルションエッセンス、パック等の皮膚用化粧料;ファンデーション、口紅、アイシャドー、チークカラー等のメイクアップ化粧料;クレンジングオイル、クレンジングクリーム等の洗浄用化粧料;シャンプー、コンディショナー等の毛髪用化粧料;入浴剤等の種々の形状の化粧料とすることができる。
本発明の化粧料には、本発明の特徴を損なわない範囲で、抗しわ・抗老化剤、抗炎症剤、肌荒れ防止剤、細胞賦活・創傷治癒剤、美白剤等の活性成分や、油剤(動植物性油脂、ロウ、エステル、高級脂肪酸、高級脂肪族アルコール等)、界面活性剤、溶剤、増粘剤、保湿剤、抗酸化剤、防腐剤、pH調整剤、顔料、香料等、化粧料に一般的に使用される添加剤を添加することができる。
本発明の飼料又は飼料添加物は、油剤、懸濁剤、乳剤、ゲル、粉末、顆粒、錠剤等の形態とすることができる。
本発明の飼料又は飼料添加物としては、ペットフード、畜産又は水産養殖飼料添加物等が挙げられる。
本発明の飼料又は飼料用添加物は、本発明の化合物を、飼料用賦形物質、希釈物質等と混合して、通常の方法に従って調製することができる。
飼料用賦形物質、希釈物質は、本発明の特徴を損なわない限り、特に制限なく用いることができ、例えば、アラビアゴム、カラギーナン、寒天、キサンタンガム、キトサン、セルロース、ローカストビーンガム等の多糖;ブドウ糖、乳糖、麦芽糖、白糖等の単糖または二糖;グリセリン、ソルビトール、D-マンニトール等の糖アルコール;アルブミン、カゼイン、グルテン、ゼラチン等のタンパク質;きな粉、小麦粉、大豆粉、トウモロコシ粉等の穀物粉;トルラ酵母、パン酵母、ビール酵母等の酵母;硬化油、植物性油脂、動物性油脂等の油脂;カオリン、ゼオライト、タルク、バーミキュライト、ベントナイト等の粘土鉱物;珪藻土、含水二酸化ケイ素、ケイ酸、軽質無水ケイ酸、無水ケイ酸、ケイ酸カルシウム、ケイ酸マグネシウム等のケイ酸またはその塩;軽質流動パラフィン、流動パラフィン等の炭化水素;カルナウバロウ等のロウ等が挙げられる。
また、さらに、本発明の飼料又は飼料添加物には、本発明の特徴を損なわない限り、グリシン、DL-アラニン、L-グルタミン酸ナトリウム等のアミノ酸又はその塩;L-アスコルビン酸、エルゴカルシフェロール、塩酸チアミン、コレカルシフェロール、ビタミンA粉末、ビタミンD粉末、リボフラビン等のビタミン;塩化カリウム、クエン酸鉄、グルコン酸カルシウム等のミネラル;アスタキサンチン、カンタキサンチン等の色素等、栄養成分補給用の添加剤を添加することができる。
高分解能質量スペクトル解析は、株式会社島津製作所製高速液体クロマトグラフ質量分析計(LCMS)(LCMS-2020)を用いて実施した。
融点(mp)測定は、株式会社アナテック・ヤナコ製融点測定器(MP-J3)を用いて行った。
100mLの反応容器(メジウム瓶)にHYA(5g)、エステル交換酵素(リパーゼ)(ノボザイムズ(Novozymes)社、リポザイム(Lipozyme) RMIM、1g)、エタノール(5g)を投入し、反応系の気相部分を窒素ガスで置換した後、40℃で28時間、撹拌した。ろ紙を用いてエステル交換酵素をろ過して除去した後、濃縮することにより、10-ヒドロキシ-シス-12-オクタデセン酸エチル(5.5g;収率100%)を得た。
融点:-20℃以下;
1H NMR(CDCl3,500MHz):(δ)ppm:0.89(t,3H,J=6.9Hz),1.30(m,19H),1.46(m,2H),1.61(tt,2H,J=7.3,7.3Hz),2.05(dt,2H,J=7.0,7.3Hz),2.21(dd,2H,J=6.8,6.8Hz),2.28(t,2H,J=7.6Hz),3.61(tt,1H,J=5.9,6.0Hz),4.12(q,2H,J=7.2Hz),5.40(dt,1H,J=7.5,11.0Hz),5.57(dt,1H,J=7.4,10.9Hz);
MS(ESI):M+326。
100mLの反応容器(メジウム瓶)にHYA(0.5g)、エステル交換酵素(リパーゼ)(ノボザイムズ(Novozymes)社、リポザイム(Lipozyme) RMIM、0.1g)、プロパノール(0.5g)を投入し、反応系の気相部分を窒素ガスで置換した後、40℃で14.5時間、撹拌した。ろ紙を用いてエステル交換酵素をろ過して除去した後、濃縮することにより、10-ヒドロキシ-シス-12-オクタデセン酸プロピル(0.5g;収率88%)を得た。
融点:-20℃以下;
1H NMR(CDCl3,500MHz):(δ)ppm:0.89(t,3H,J=6.9Hz),0.95(t,3H,J=7.4Hz),1.30(m,16H),1.47(m,2H),1.64(m,4H),2.05(dt,2H,J=5.7,7.6Hz),2.21(dd,2H,J=6.6,6.6Hz),2.30(t,2H,J=7.6Hz),3.61(tt,1H,J=5.9,6.0Hz),4.02(t,2H,J=6.7Hz),5.40(dt,1H,J=6.8,10.9Hz),5.57(dt,1H,J=7.3,10.9Hz);
MS(ESI):M+340。
100mLの反応容器(メジウム瓶)にHYA(0.5g)、エステル交換酵素(リパーゼ)(ノボザイムズ(Novozymes)社、リポザイム(Lipozyme) RMIM、0.1g)、エチレングリコール(260.7mg)を投入し、反応系の気相部分を窒素ガスで置換した後、40℃で72時間、撹拌した。ろ紙を用いてエステル交換酵素をろ過して除去した後、中圧シリカゲルクロマトグラフィー(「フラッシュ自動精製装置 Isolera One」、バイオタージ(Biotage)社製、カラム:「SNAP Ultra」、バイオタージ(Biotage)社製、ヘキサン:酢酸エチル=90:10~50:50で溶出)により単離精製し、エチレングリコールモノ10-ヒドロキシ-シス-12-オクタデセン酸エステル(315.6mg)及びエチレングリコールジ10-ヒドロキシ-シス-12-オクタデセン酸エステル(152.7mg)を得た。
エチレングリコールモノ10-ヒドロキシ-シス-12-オクタデセン酸エステル
融点:8~9℃以下;
1H NMR(CDCl3,500MHz):(δ)ppm:
0.89(t,3H,J=7.0Hz),1.30(m,16H),1.46(m,2H),1.63(tt,2H,J=7.3,7.3Hz),1.84(brs,1H),2.05(dt,2H,J=5.2,6.5Hz),2.21(dd,2H,J=6.5,6.5Hz),2.35(t,2H,J=7.5Hz),3.48(brs,1H),3.61(tt,1H,J=5.8,6.2Hz),4.21(t,2H,J=1.7Hz),5.40(dt,1H,J=7.5,11.0Hz),5.57(dt,1H,J=7.4,10.9Hz);
MS(ESI):M+342。
エチレングリコールジ10-ヒドロキシ-シス-12-オクタデセン酸エステル
融点:22℃;
1H NMR(CDCl3,500MHz):(δ)ppm:
0.89(t,6H,J=7.0Hz),1.30(m,32H),1.46(m,4H),1.62(tt,4H,J=7.1,9.1Hz),2.05(dt,4H,J=6.1,7.4Hz),2.21(dd,4H,J=6.7,6.7Hz),2.32(m,4H),3.48(brs,2H),3.61(tt,2H,J=5.8,6.3Hz),4.27(brs,4H),5.40(dt,2H,J=7.5,11.0Hz),5.57(dt,2H,J=7.3,11.0Hz);
MS(ESI):M+623。
比較例として、特許文献2に記載の方法により調製したHYAを用いた。
実施例1及び2の化合物、並びに比較例のHYAが、常温(15℃~25℃)で液体であるか、固体であるかについて、目視することにより確認した。
従って、10-ヒドロキシ-シス-12-オクタデセン酸(HYA)をエチルエステル又はプロピルエステルとした本発明の化合物は、常温において液体状態で存在することが分かった。
実施例1の化合物と、比較例のHYAの風味について、パネラー(10名)による官能評価(以下味覚試験という)を実施した。パネラーは、5mgの試料(試料名は、試験時にパネラーに対して秘匿した)を摂取した後に、五味(旨味・苦味・酸味・塩味・甘味)、刺激性及び油臭を評価し、さらに総合評価を行った。
各評価は、次の通り5段階の評価とし、10名のパネラーの評価点の平均値を算出した。
五味(旨味・苦味・酸味・塩味・甘味):強い(5点)~弱い(1点)
刺激性:弱い(5点)~強い(1点)
油臭:弱い(5点)~強い(1点)
総合評価:うまい(5点)~まずい(1点)
Claims (13)
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体(但し、10-ヒドロキシ-シス-12-オクタデセン酸メチル及び10-ヒドロキシ-シス-12-オクタデセン酸エチルは除く)。
- 常温で液体である、請求項1に記載の10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、食用油脂。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、食品又は食品添加物。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、医薬組成物。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、肥満、糖尿病、脂質代謝異常、高脂血症、脂肪肝、潰瘍性大腸炎、クローン病、潰瘍、過敏性腸症候群及び炎症性疾患からなる群から選択される疾患の予防又は治療剤。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、化粧料又は化粧料添加物。
- 10-ヒドロキシ-シス-12-オクタデセン酸アルキルエステル又はその光学異性体を含有することを特徴とする、飼料又は飼料添加物。
- 10-ヒドロキシ-シス-12-オクタデセン酸と二価アルカノールとのエステル又はその光学異性体。
- 常温で液体である、請求項9に記載のエステル又はその光学異性体。
- 請求項9又は10に記載のエステル又はその光学異性体を含有する、食品又は食品添加物。
- 請求項9又は10に記載のエステル又はその光学異性体を含有する、医薬組成物。
- 請求項9又は10に記載のエステル又はその光学異性体を含有する、化粧料又は化粧料添加物。
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JP2017522248A JP6806340B2 (ja) | 2015-06-02 | 2016-06-02 | 10−ヒドロキシ−シス−12−オクタデセン酸アルキルエステル及びその用途 |
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WO2023063175A1 (ja) * | 2021-10-13 | 2023-04-20 | 株式会社J-オイルミルズ | 水添臭付与剤、その製造方法、食品に水添臭を付与する方法、食品に水添臭を付与するための酸化処理物の使用、及び水添臭付与剤を含む食品 |
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