JPH01121253A - Inclusion compound of ethanolamine derivative and production thereof - Google Patents
Inclusion compound of ethanolamine derivative and production thereofInfo
- Publication number
- JPH01121253A JPH01121253A JP28005787A JP28005787A JPH01121253A JP H01121253 A JPH01121253 A JP H01121253A JP 28005787 A JP28005787 A JP 28005787A JP 28005787 A JP28005787 A JP 28005787A JP H01121253 A JPH01121253 A JP H01121253A
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- higher fatty
- fatty acid
- acyl group
- ethanolamine derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 46
- 150000002169 ethanolamines Chemical class 0.000 title claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 64
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 51
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 41
- 239000000194 fatty acid Substances 0.000 claims abstract description 41
- 229930195729 fatty acid Natural products 0.000 claims abstract description 41
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 41
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 125000002252 acyl group Chemical group 0.000 claims abstract description 27
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 150000005671 trienes Chemical class 0.000 claims abstract description 21
- 229960003512 nicotinic acid Drugs 0.000 claims abstract description 16
- 235000001968 nicotinic acid Nutrition 0.000 claims abstract description 16
- 239000011664 nicotinic acid Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 239000000243 solution Substances 0.000 claims abstract description 10
- 239000012298 atmosphere Substances 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 11
- 239000001116 FEMA 4028 Substances 0.000 claims description 9
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 9
- 229960004853 betadex Drugs 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 238000004898 kneading Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims description 4
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims description 4
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims description 4
- 229960004488 linolenic acid Drugs 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 claims description 2
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 claims description 2
- 235000020664 gamma-linolenic acid Nutrition 0.000 claims description 2
- 229960002733 gamolenic acid Drugs 0.000 claims description 2
- 239000012456 homogeneous solution Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 210000001772 blood platelet Anatomy 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 229940126062 Compound A Drugs 0.000 description 9
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 125000000627 niacin group Chemical group 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- XUGISPSHIFXEHZ-UHFFFAOYSA-N 3beta-acetoxy-cholest-5-ene Natural products C1C=C2CC(OC(C)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 XUGISPSHIFXEHZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000555825 Clupeidae Species 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 241001274189 Pomatomus saltatrix Species 0.000 description 2
- 241000269821 Scombridae Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- XUGISPSHIFXEHZ-VEVYEIKRSA-N cholesteryl acetate Chemical compound C1C=C2C[C@@H](OC(C)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 XUGISPSHIFXEHZ-VEVYEIKRSA-N 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000020640 mackerel Nutrition 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 235000019512 sardine Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- -1 γ-CD Chemical compound 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、新規化合物およびその製法に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to a novel compound and a method for producing the same.
即ちエタノールアミン誘導体をシクロデキストリンと反
応させることを特徴とするエタノールアミン誘導体シク
ロデキストリン包接化合物およびその製法に関する。That is, the present invention relates to an ethanolamine derivative cyclodextrin clathrate compound characterized by reacting an ethanolamine derivative with a cyclodextrin, and a method for producing the same.
従来、−殺伐Ｒ’ ＮＨＣＨ２ＣＨ２ＯＲ２（式中Ｒ
１は水素原子を示すか若しくはＲ１はニコチン酸。Conventionally, -R' NHCH2CH2OR2 (R in the formula
1 represents a hydrogen atom or R1 is nicotinic acid.
トリエン高級脂肪酸およびペンタエン高級脂肪酸のいず
れかから誘導されるアシル基を示し、Ｒ２は水素原子を
示すか若しくはＲ２はニコチン酸、トリエン高級脂肪酸
およびペンタエン高級脂肪酸のいずれかから誘導される
アシル基を示す）で表されるエタノールアミン誘導体は
、強力な血小板凝集抑制作用を有し、血小板凝集に起因
する疾患即ち血栓症やガン転移等の予防剤として有用で
あることが判っていた。It represents an acyl group derived from either triene higher fatty acid or pentaene higher fatty acid, and R2 represents a hydrogen atom, or R2 represents an acyl group derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid. It was known that the ethanolamine derivative represented by ) has a strong platelet aggregation inhibitory effect and is useful as a preventive agent for diseases caused by platelet aggregation, such as thrombosis and cancer metastasis.
エタノールアミン誘導体は、ニコチン酸またはトリエン
高級脂肪酸またはペンタエン高級脂肪酸あるいはこれら
の反応性誘導体とエタノールアミンとを縮合させること
により得られる。縮合剤としては、例えばクロル炭酸エ
チルが好適に用いられる。Ethanolamine derivatives are obtained by condensing nicotinic acid, triene higher fatty acids, pentaene higher fatty acids, or reactive derivatives thereof with ethanolamine. As the condensing agent, for example, ethyl chlorocarbonate is preferably used.
前記反応性誘導体としてはカルボン酸のチアゾリジンチ
オンアミド誘導体等がある。また、エタノールアミン誘
導体は、前記縮合反応に続いてアルコール性水酸基に対
してトリエン高級脂肪酸またはペンタエン高級脂肪酸を
縮合反応させることによって得られる。Examples of the reactive derivatives include thiazolidine thionamide derivatives of carboxylic acids. Further, the ethanolamine derivative can be obtained by subjecting the alcoholic hydroxyl group to a condensation reaction with a triene higher fatty acid or a pentaene higher fatty acid following the above condensation reaction.
本発明のエタノールアミン誘導体は、α−リノレン酸あ
るいはγ−リノレン酸等のトリエン高級脂肪酸から誘導
されるアシル基またはエイコサペンタエン酸等のペンタ
エン高級脂肪酸から誘導されるアシル基を分子中に有す
るため、光や酸素による影響を受けやすく、安定性に欠
ける上に水溶性にも欠けた。また、エイコサペンタエン
酸から誘導されたアシル基はイワシ、サバ等の青色魚特
有の臭気を有した。Since the ethanolamine derivative of the present invention has an acyl group derived from a triene higher fatty acid such as α-linolenic acid or γ-linolenic acid or an acyl group derived from a pentaene higher fatty acid such as eicosapentaenoic acid in the molecule, It was easily affected by light and oxygen, lacked stability, and lacked water solubility. Furthermore, the acyl group derived from eicosapentaenoic acid had an odor characteristic of blue fish such as sardines and mackerel.
更に融点が低く、常温で液体であるため固形剤として製
剤にするのが困難であった。Furthermore, it has a low melting point and is liquid at room temperature, making it difficult to prepare it as a solid preparation.
本発明は、光、酸素に対する安定性に優れ、水に溶は易
く、臭気を抑制し製剤性に優れたエタノールアミン誘導
体包接化合物を提供することを目的とする。An object of the present invention is to provide an ethanolamine derivative clathrate compound that has excellent stability against light and oxygen, is easily soluble in water, suppresses odor, and has excellent formulation properties.
本発明は上記目的を達成するため次のような構成とした
。即ち本発明は
（１）−殺伐Ｒ’ ＮＨ’ＣＨｚＣＨｚ ＯＲ２（
式中１７１は水素原子を示すか若しくはＲ１はニコチン
酸、トリエン高級脂肪酸およびペンタエン高級脂肪酸の
いずれかから誘導されるアシル基を示し、Ｒ２は゛水素
原子を示すか若しくはＲｔはニコチン酸、トリエン高級
脂肪酸およびペンタエン高級脂肪酸のいずれかから誘導
されるアシル基を示す）で表されるエタノールアミン誘
導体のシクロデキストリン包接化合物。In order to achieve the above object, the present invention has the following configuration. That is, the present invention provides (1) - R'NH'CHzCHz OR2 (
In the formula, 171 represents a hydrogen atom, or R1 represents an acyl group derived from nicotinic acid, a triene higher fatty acid, or a pentaene higher fatty acid, and R2 represents a hydrogen atom, or Rt represents a nicotinic acid, a triene higher fatty acid. and a cyclodextrin clathrate compound of an ethanolamine derivative (indicating an acyl group derived from either a pentaene or higher fatty acid).
（２）トリエン高級脂肪酸から誘導されるアシル基がα
−リノレン酸あるいはＴ−リノレン酸から誘導されるア
シル基である第１項記載のシクロデキストリン包接化合
物。(2) The acyl group derived from triene higher fatty acid is α
- The cyclodextrin clathrate compound according to item 1, which is an acyl group derived from linolenic acid or T-linolenic acid.
（３）ペンタエン高級脂肪酸から誘導されるアシル基が
エイコサペンタエン酸から誘導されるアシル基である第
１項記載のシクロデキストリン包接化合物。(3) The cyclodextrin clathrate compound according to item 1, wherein the acyl group derived from pentaene higher fatty acid is an acyl group derived from eicosapentaenoic acid.
（４）シクロデキストリンがβ−シクロデキストリンで
ある第１項乃至第３項のいずれかに記載のシクロデキス
トリン包接化合物。(4) The cyclodextrin clathrate compound according to any one of items 1 to 3, wherein the cyclodextrin is β-cyclodextrin.
（５）シクロデキストリンが分岐シクロデキストリンで
ある第１項乃至第３項のいずれかに記載のシクロデキス
トリン包接化合物。(5) The cyclodextrin clathrate compound according to any one of items 1 to 3, wherein the cyclodextrin is a branched cyclodextrin.
（６）シクロデキストリン水溶液と一般式％式％
（式中ｎｌは水素原子を示すか若しくはＲ１はニコチン
酸、トリエン高級脂肪酸およびペンタエン高級脂肪酸の
いずれかから誘導されるアシル基を示し、Ｒ２は水素原
子を示すか若しくはＲ２はニコチン酸、トリエン高級脂
肪酸およびペンタエン高級脂肪酸のいずれかから誘導さ
れるアシル基を示す）で表されるエタノールアミン誘導
体の有機溶媒溶液とを、酸素を実質的に含まない雰囲気
下で混合し、加熱して実質的に均質な溶液とした後、徐
々に室温まで冷却することを特徴とするエタノールアミ
ン誘導体のシクロデキストリン包接化合物の製法。(6) Cyclodextrin aqueous solution and general formula % formula % (in the formula, nl represents a hydrogen atom or R1 represents an acyl group derived from either nicotinic acid, triene higher fatty acid or pentaene higher fatty acid, and R2 represents hydrogen or R2 represents an acyl group derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid) in an organic solvent solution containing substantially no oxygen. A method for producing a cyclodextrin clathrate compound of an ethanolamine derivative, which comprises mixing in an atmosphere, heating to form a substantially homogeneous solution, and then gradually cooling to room temperature.
（７）該エタノールアミン誘導体１モルに対しシクロデ
キストリン１〜１０モルを反応させる製法。(7) A production method in which 1 to 10 moles of cyclodextrin are reacted with 1 mole of the ethanolamine derivative.
（８）有機溶媒がアセトン、メタノール、エタノール、
イソプロパノールおよびテトラヒドロフランよりなる群
の中から選ばれた製法。(8) Organic solvent is acetone, methanol, ethanol,
A manufacturing method selected from the group consisting of isopropanol and tetrahydrofuran.
（９）シクロデキストリンと該シクロデキストリンに対
して０．５〜１０重量部の水と、前記シクロデキストリ
ンに対して実質的に等モル以下の一般式
％式％
（式中Ｒ１は水素原子を示すか若しくはＲ１はニコチン
酸、トリエン高級脂肪酸およびペンタエン高級脂肪酸の
いずれかから誘導されるアシル基を示し、Ｒｔは水素原
子を示すか若しくはＲ２はニコチン酸、トリエン高級脂
肪酸およびペンタエン高級脂肪酸のいずれかから誘導さ
れるアシル基を示す）で表されるエタノールアミン誘導
体とを酸素を実質的に含まない雰囲気下で混練すること
を特徴とするエタノールアミン誘導体のシクロデキスト
リン包接化合物の製法。(9) Cyclodextrin, 0.5 to 10 parts by weight of water based on the cyclodextrin, and substantially equal moles or less of the general formula % formula % (wherein R1 represents a hydrogen atom). or R1 represents an acyl group derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid; Rt represents a hydrogen atom; or R2 represents nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid. A method for producing a cyclodextrin clathrate compound of an ethanolamine derivative, which comprises kneading an ethanolamine derivative represented by (indicating an acyl group to be derived) in an atmosphere substantially free of oxygen.
（１０）該エタノールアミン誘導体１モルに対しシクロ
デキストリン１〜１０モルを反応させる製法。(10) A production method in which 1 to 10 moles of cyclodextrin are reacted with 1 mole of the ethanolamine derivative.
から構成されるものである。It consists of:
本発明の包接化合物の容体（ゲスト）であるエタノール
アミン誘導体は例えば式
で示される分子量４５０．黄色〜橙黄色の油状物質で、
わずかにイワシ、サバなどの青色生魚特有の臭気を有し
ている。そして、有機溶媒には溶は易く、水にはほとん
ど溶けない。また、光、酸素により容易に分解されて赤
味を呈するとともに特有の臭気を発する。その他に例え
ば次のような化合物がある。The ethanolamine derivative that is the host (guest) for the clathrate compound of the present invention has a molecular weight of 450. A yellow to orange-yellow oily substance,
It has a slight odor characteristic of raw blue fish such as sardines and mackerel. It is easily soluble in organic solvents and almost insoluble in water. It is also easily decomposed by light and oxygen, giving off a reddish color and a unique odor. Other examples include the following compounds:
本発明でいうシクロデキストリン（ＣＤ）とは、澱粉、
アミロースなどからシクロデキストリングルクツトラン
スフェラーゼ等によって生成されるα−ＣＤ、β−ＣＤ
、 γ−ＣＤなどのＣＤ、またはＣＤとマルトースを
原料とし、プルラナーゼを利用してＣＤにマルトースを
結合させたマルトシルＣＤ（イソエリート０塩水港精糖
■製）などを示す。Cyclodextrin (CD) in the present invention refers to starch,
α-CD and β-CD produced from amylose etc. by cyclodextrin luctutransferase etc.
, CD such as γ-CD, or maltosil CD (manufactured by Isoelite 0 Shisui Minato Seito), which uses CD and maltose as raw materials and binds maltose to CD using pullulanase.
本発明はこのシクロデキストリンに前述のエタノールア
ミン誘導体を包接させた化合物に関するものである。包
接化合物の製法としては、溶液法。The present invention relates to a compound in which the above-mentioned ethanolamine derivative is included in this cyclodextrin. The method for producing clathrate compounds is the solution method.
混練法が適宜使用できる。A kneading method can be used as appropriate.
溶液法では、シクロデキストリンの水溶液を作り、これ
を穏やかに加温したエタノールアミン誘導体の有機溶媒
溶液に徐々に加え、２〜６時間撹拌して包接化合物を沈
澱として得る。In the solution method, an aqueous solution of cyclodextrin is prepared, and this is gradually added to a gently heated solution of an ethanolamine derivative in an organic solvent, and the mixture is stirred for 2 to 6 hours to obtain the clathrate compound as a precipitate.
一方混練法では、シクロデキストリンに約０．５〜１０
重量部の水を加えペースト状にし、次にシクロデキスト
リンに対して実質的に等モル量以下のエタノールアミン
誘導体を加えて十分に混練する。On the other hand, in the kneading method, cyclodextrin contains about 0.5 to 10
Parts by weight of water are added to form a paste, and then an ethanolamine derivative in a substantially equimolar amount or less relative to the cyclodextrin is added and thoroughly kneaded.
混練する時間は１〜１２時間、好ましくは２〜６時間で
あり、その時の温度は好ましくは室温（１０〜３５°Ｃ
）である。The kneading time is 1 to 12 hours, preferably 2 to 6 hours, and the temperature at that time is preferably room temperature (10 to 35°C).
).
溶液法および混練法ともに、実質的に酸素を含まない雰
囲気下で行うことが好ましい。実質的に酸素を含まない
雰囲気下とは、不活性ガス、窒素。Both the solution method and the kneading method are preferably carried out in an atmosphere substantially free of oxygen. An atmosphere substantially free of oxygen is an inert gas, nitrogen.
酸素を除去した空気等で置換した状態を示す。This shows the state in which the air is replaced with air, etc. from which oxygen has been removed.
また、本発明に使用される有機溶媒としては、水に可溶
性でありシクロデキストリンと強固な包接化合物を形成
しないものであればよく、例えばアセトン、メタノール
、エタノール、イソプロパノール、テトラヒドロフラン
などがあげられる。Further, the organic solvent used in the present invention may be any solvent as long as it is soluble in water and does not form a strong clathrate with cyclodextrin, such as acetone, methanol, ethanol, isopropanol, and tetrahydrofuran.
混練法においても少量の有機溶媒を添加してもよい。A small amount of organic solvent may also be added in the kneading method.
包接化が終了したのち、含水アルコールで洗浄し、減圧
乾燥して粉末状包接化合物を得る。After the clathration is completed, the mixture is washed with hydrous alcohol and dried under reduced pressure to obtain a powdery clathrate compound.
得られた粉末は大気中に放置しても赤味を呈することが
なく、更に臭気もほとんどなく変質５酸敗を受けにくい
ことも判明した。It was also found that the obtained powder did not develop a reddish color even when left in the air, had almost no odor, and was not susceptible to rancidity.
また、得られた粉末はそのままあるいは通常の方法で製
剤担体あるいは賦形剤と混合され、錠剤。The obtained powder may be used as it is or mixed with a pharmaceutical carrier or excipient in a conventional manner to form a tablet.
散剤、カプセル剤、顆粒剤に製剤化される。担体あるい
は賦形剤の例として澱粉、乳糖、結晶セルロース、タル
ク、ステアリン酸マグネシウム等があげられる。本発明
の化合物は、上記の固形製剤の他に液剤、乳化剤とする
こともできる。It is formulated into powders, capsules, and granules. Examples of carriers or excipients include starch, lactose, crystalline cellulose, talc, magnesium stearate, and the like. In addition to the above-mentioned solid preparations, the compound of the present invention can also be made into liquid preparations and emulsifiers.
次に実施例により本発明の詳細な説明する。Next, the present invention will be explained in detail with reference to Examples.
実施例１
エタノールアミン誘導体−シクロデキストリン包接化合
物の調製。Example 1 Preparation of ethanolamine derivative-cyclodextrin clathrate.
化合物Ａ ２７■（０，０６ミリモル）を０．３ｍｌ
のエタノールに溶解した溶液に、別にβ−シクロデキス
トリン２１０ ｍｇ（０，３ミリモル）を水４．７ｍｆ
ｌに加温溶解して調整した溶液を加え、５０°Ｃで加温
溶解した後、徐々に室温まで冷却すると沈澱が析出する
。0.3 ml of compound A 27■ (0.06 mmol)
Separately, 210 mg (0.3 mmol) of β-cyclodextrin was dissolved in 4.7 mf of water.
Add the solution prepared by heating and dissolving the solution in 100°C, heat and dissolve at 50°C, and then gradually cool to room temperature to form a precipitate.
これを室温で一夜放置後濾過し、５０％エタノール水溶
液で洗浄し、減圧乾燥しエタノールアミン誘導体シクロ
デキストリン包接化合物を得た。This was left overnight at room temperature, filtered, washed with a 50% aqueous ethanol solution, and dried under reduced pressure to obtain an ethanolamine derivative cyclodextrin clathrate compound.
白色粉末状結晶、融点３００°Ｃ以上であった。It was a white powdery crystal with a melting point of 300°C or higher.
また、β−シクロデキストリンの代りにマルトシル−シ
クロデキストリンを用いたものについても８両型した。Eight types were also prepared using maltosyl-cyclodextrin instead of β-cyclodextrin.
更に、化合物Ｂ、Ｃ，Ｄについても同様に操作し包接化
合物を得た。Furthermore, compounds B, C, and D were operated in the same manner to obtain clathrate compounds.
この包接化合物中のエタノールアミン誘導体の含量は、
次の方法により測定した。包接化合物の約５０■をはか
りとり、水ＩＭを加えて溶解させた後、酢酸エチル１０
ｍで２回抽出し、抽出液を減圧乾固する。残留物をエタ
ノールに熔解し、２６３ｎｍの吸光度を測定することに
より求めた。その結果を第１表に示した。The content of ethanolamine derivative in this clathrate is
It was measured by the following method. Weigh out about 50 μm of the clathrate, add water IM to dissolve it, and add 10 μm of ethyl acetate.
Extract twice with m and dry the extract under reduced pressure. It was determined by dissolving the residue in ethanol and measuring the absorbance at 263 nm. The results are shown in Table 1.
さらに、化合物Ａのβ−ＣＤ包接化合物の赤外線吸収ス
ペクトルを測定した。その結果を第１図に示した。Furthermore, the infrared absorption spectrum of the β-CD clathrate of Compound A was measured. The results are shown in Figure 1.
第 １ 表
第１表の結果から明らかなように、包接化合物はＣＤの
種類に係わりなく生成し、包接化合物中に含まれるエタ
ノールアミン誘導体の量は約５０％であった。また、こ
れらの包接化合物を０．５Ｗ／Ｖ％になるように水に溶
解させたところ、いずれも容易に溶解することが判った
。Table 1 As is clear from the results in Table 1, the clathrate compound was produced regardless of the type of CD, and the amount of ethanolamine derivative contained in the clathrate compound was about 50%. Furthermore, when these clathrate compounds were dissolved in water to a concentration of 0.5 W/V%, it was found that all of them were easily dissolved.
実施例２
エタノールアミン誘導体−シクロデキストリン包接化合
物の調製。Example 2 Preparation of ethanolamine derivative-cyclodextrin clathrate.
β−シクロデキストリン１０５ｇに水１１１ｄ及び化合
物Ａ２７ｇを加えて密栓し、室温下で５時間混練した。111 d of water and 27 g of compound A were added to 105 g of β-cyclodextrin, the mixture was tightly stoppered, and the mixture was kneaded at room temperature for 5 hours.
その後、濾紙を用いて吸引濾過し、水およびエタノール
で洗浄した後、乾燥し包接化合物を得た。また、βシク
ロデキストリンの代りにマルトシル−シクロデキストリ
ンを用いたものについても調製した。Thereafter, the mixture was suction filtered using filter paper, washed with water and ethanol, and then dried to obtain a clathrate compound. Furthermore, a product using maltosyl-cyclodextrin instead of β-cyclodextrin was also prepared.
更に、化合物Ｂ、Ｃ，Ｄについても同様に操作し包接化
合物を得た。Furthermore, compounds B, C, and D were operated in the same manner to obtain clathrate compounds.
これらの包接化合物中のエタノールアミン誘導体の含量
は第２表に示した。The content of ethanolamine derivatives in these clathrates is shown in Table 2.
イアトロスキャンによる化合物Ａのβ−シクロデキスト
リン包接化合物の分析の１例を第２図に示した。An example of the analysis of the β-cyclodextrin clathrate compound of Compound A using IATROSCAN is shown in FIG.
（以下余白）
第２表の結果から明らかなように、包接化合物はＣＤの
種類に係わりな（生成し、包接化合物中に含まれるエタ
ノールアミン誘導体の量は約５０％であった。また、こ
れらの包接化合物を０．５Ｗ／Ｖ％になるように水に溶
解させたところ、いずれも容易に溶解することが判った
。(Left below) As is clear from the results in Table 2, clathrates were formed regardless of the type of CD, and the amount of ethanolamine derivatives contained in the clathrates was approximately 50%. When these clathrate compounds were dissolved in water to a concentration of 0.5 W/V%, it was found that all of them were easily dissolved.
安定性試験
実施例１および２で調製した化合物Ａの包接化合物を４
０°Ｃ下に保存し化合物Ａの残存率を測定した。その結
果を第３表に示した。The clathrate compound of Compound A prepared in Stability Test Examples 1 and 2 was
It was stored at 0°C and the residual rate of Compound A was measured. The results are shown in Table 3.
測定は包接化合物中の含有量測定時と同様に抽出、乾固
した後コレステロールアセテートを内部標準物質として
加え、クロロホルムで溶解しイアトロスキャン（イアト
ロスキャンＴ）Ｉ−１０，＠ヤトロン製）を用い下記の
条件下で行った。The measurement was carried out in the same manner as when measuring the content in clathrate compounds, after extraction and drying, cholesterol acetate was added as an internal standard substance and dissolved in chloroform. The test was carried out under the following conditions.
展開条件（３段階に展開）
■ クロロホルム：メタノール（９： １ 、 Ｖ／Ｖ
）３ｃｍ展開
■ ｎ−へキサン：ジエチルエーテル：ギ酸（７０：３
０：１） ６ ｃ＋ａ展開
■ ｎ−ヘキサン：ジエチルエーテル（７０： ３）１
０ｃｍ展開
ロッド
クロマトロッドＳ■
イアトロスキャン
Ｈ！流量０．８ｋｇ／ｃ＋＋ｔ
（以下余白）
第 ３ 表
第３表の結果から明らかなように、包接化合物はＣＤの
種類、調製の方法に係わりなく、優れた経時的安定性を
示した。また、比較例では保存日数が増すに従って臭気
が激しくなったが、本発明の包接化合物ではかすかな臭
気を有するだけであった。Development conditions (deployed in 3 steps) ■ Chloroform:methanol (9:1, V/V
) 3cm development ■ n-hexane: diethyl ether: formic acid (70:3
0:1) 6 c+a expansion■ n-hexane:diethyl ether (70:3)1
0cm deployment rod Chromatorod S ■ Iatoroscan H! Flow rate: 0.8 kg/c++t (blank below) Table 3 As is clear from the results in Table 3, the clathrate compound showed excellent stability over time, regardless of the type of CD or the method of preparation. Furthermore, in the comparative example, the odor became more intense as the number of days of storage increased, but the clathrate compound of the present invention only had a faint odor.
表に示さないが他の包接化合物においてもほぼ同様の経
時的安定性を示した。Although not shown in the table, other clathrate compounds also showed almost similar stability over time.
本発明によれば新規なエタノールアミン誘導体包接化合
物およびその製法が提供される。According to the present invention, a novel ethanolamine derivative clathrate compound and a method for producing the same are provided.
本発明のエタノールアミン誘導体包接化合物は、エタノ
ールアミン誘導体がその構造中にトリエンあるいはペン
タエン高級脂肪酸から誘導されたアシル基を有するため
に本質的に有していた、光および酸素に対する不安定さ
を著しく改善した。その上、エタノールアミン誘導体自
体の低融点に起因する熱に対する不安定さおよび製剤化
の困難性を改善することができた。The ethanolamine derivative clathrate compound of the present invention has the inherent instability to light and oxygen due to the acyl group derived from triene or pentaene higher fatty acids in its structure. Significant improvement. Furthermore, it was possible to improve the thermal instability and difficulty in formulation caused by the low melting point of the ethanolamine derivative itself.
また本発明の包接化合物は、エタノールアミン誘導体自
体が有している特有の臭気を抑制し、更に水に対する溶
解性をも付加するため、血小板凝集抑制剤の優れた製剤
原料として使用できることをも示唆するものである。Furthermore, the clathrate compound of the present invention suppresses the characteristic odor of the ethanolamine derivative itself and also has water solubility, so it can be used as an excellent pharmaceutical raw material for platelet aggregation inhibitors. It is suggestive.
第１図は、化合物Ａのβ−シクロデキストリン包接化合
物の赤外線吸収スペクトルを示し、第２図は化合物Ａの
β−シクロデキストリン包接化合物のイアトロスキャン
による分析例である。
第２図中１は内部標準物質であるコレステロールアセテ
ート、２は化合物Ａ由来のピークである。FIG. 1 shows an infrared absorption spectrum of the β-cyclodextrin clathrate of Compound A, and FIG. 2 is an example of analysis of the β-cyclodextrin clathrate of Compound A by IATROScan. In FIG. 2, 1 is a peak derived from cholesterol acetate, which is an internal standard substance, and 2 is a peak derived from compound A.
Claims (10)
＾２（式中Ｒ＾１は水素原子を示すか若しくはＲ＾１は
ニコチン酸、トリエン高級脂肪酸およびペンタエン高級
脂肪酸のいずれかから誘導されるアシル基を示し、Ｒ＾
２は水素原子を示すか若しくはＲ＾２はニコチン酸、ト
リエン高級脂肪酸およびペンタエン高級脂肪酸のいずれ
かから誘導されるアシル基を示す）で表されるエタノー
ルアミン誘導体のシクロデキストリン包接化合物。(1) General formula R^1-NH-CH_2CH_2-O-R
^2 (In the formula, R^1 represents a hydrogen atom or R^1 represents an acyl group derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid, R^1
2 represents a hydrogen atom, or R^2 represents an acyl group derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid). A cyclodextrin clathrate compound of an ethanolamine derivative.
−リノレン酸あるいはγ−リノレン酸から誘導されるア
シル基である特許請求の範囲第１項記載のシクロデキス
トリン包接化合物。(2) The acyl group derived from triene higher fatty acid is α
The cyclodextrin clathrate compound according to claim 1, which is an acyl group derived from -linolenic acid or γ-linolenic acid.
エイコサペンタエン酸から誘導されるアシル基である特
許請求の範囲第１項記載のシクロデキストリン包接化合
物。(3) The cyclodextrin clathrate compound according to claim 1, wherein the acyl group derived from pentaene higher fatty acid is an acyl group derived from eicosapentaenoic acid.
ある特許請求の範囲第１項乃至第３項のいずれかに記載
のシクロデキストリン包接化合物。(4) The cyclodextrin clathrate compound according to any one of claims 1 to 3, wherein the cyclodextrin is β-cyclodextrin.
ある特許請求の範囲第１項乃至第３項のいずれかに記載
のシクロデキストリン包接化合物。(5) The cyclodextrin clathrate compound according to any one of claims 1 to 3, wherein the cyclodextrin is a branched cyclodextrin.
＾１は水素原子を示すか若しくはＲ＾１はニコチン酸、
トリエン高級脂肪酸およびペンタエン高級脂肪酸のいず
れかから誘導されるアシル基を示し、Ｒ＾２は水素原子
を示すか若しくはＲ＾２はニコチン酸、トリエン高級脂
肪酸およびペンタエン高級脂肪酸のいずれかから誘導さ
れるアシル基を示す）で表されるエタノールアミン誘導
体の有機溶媒溶液とを、酸素を実質的に含まない雰囲気
下で混合し、加熱して実質的に均質な溶液とした後、徐
々に室温まで冷却することを特徴とするエタノールアミ
ン誘導体のシクロデキストリン包接化合物の製法。(6) Cyclodextrin aqueous solution and the general formula R^1-NH-CH_2CH_2CH_2-O-R^2 (in the formula R
^1 represents a hydrogen atom or R^1 is nicotinic acid,
Indicates an acyl group derived from either triene higher fatty acid or pentaene higher fatty acid, and R^2 represents a hydrogen atom, or R^2 is derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid. An organic solvent solution of an ethanolamine derivative (representing an acyl group) is mixed in an atmosphere substantially free of oxygen, heated to form a substantially homogeneous solution, and then gradually cooled to room temperature. A method for producing a cyclodextrin clathrate compound of an ethanolamine derivative, characterized by:
キストリン１〜１０モルを反応させる特許請求の範囲第
６項記載の製法。(7) The production method according to claim 6, wherein 1 to 10 moles of cyclodextrin are reacted with 1 mole of the ethanolamine derivative.
イソプロパノールおよびテトラヒドロフランよりなる群
の中から選ばれた特許請求の範囲第６項記載の製法。(8) Organic solvent is acetone, methanol, ethanol,
7. The method according to claim 6, wherein the isopropanol and tetrahydrofuran are selected from the group consisting of isopropanol and tetrahydrofuran.
して０．５〜１０重量部の水と、前記シクロデキストリ
ンに対して実質的に等モル以下の一般式 Ｒ＾１−ＮＨ−ＣＨ＿２ＣＨ＿２−Ｏ−Ｒ＾２（式中Ｒ
＾１は水素原子を示すか若しくはＲ＾１はニコチン酸、
トリエン高級脂肪酸およびペンタエン高級脂肪酸のいず
れかから誘導されるアシル基を示し、Ｒ＾２は水素原子
を示すか若しくはＲ＾２はニコチン酸、トリエン高級脂
肪酸およびペンタエン高級脂肪酸のいずれかから誘導さ
れるアシル基を示す）で表されるエタノールアミン誘導
体とを酸素を実質的に含まない雰囲気下で混練すること
を特徴とするエタノールアミン誘導体のシクロデキスト
リン包接化合物の製法。(9) Cyclodextrin, 0.5 to 10 parts by weight of water based on the cyclodextrin, and substantially equimolar or less of the general formula R^1-NH-CH_2CH_2-O-R^ with respect to the cyclodextrin. 2 (in the formula R
^1 represents a hydrogen atom or R^1 is nicotinic acid,
Indicates an acyl group derived from either triene higher fatty acid or pentaene higher fatty acid, and R^2 represents a hydrogen atom, or R^2 is derived from either nicotinic acid, triene higher fatty acid, or pentaene higher fatty acid. A method for producing a cyclodextrin clathrate compound of an ethanolamine derivative, which comprises kneading an ethanolamine derivative represented by (representing an acyl group) in an atmosphere substantially free of oxygen.
デキストリン１〜１０モルを反応させる特許請求の範囲
第９項記載の製法。(10) The production method according to claim 9, wherein 1 to 10 moles of cyclodextrin are reacted with 1 mole of the ethanolamine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28005787A JPH01121253A (en) | 1987-11-05 | 1987-11-05 | Inclusion compound of ethanolamine derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28005787A JPH01121253A (en) | 1987-11-05 | 1987-11-05 | Inclusion compound of ethanolamine derivative and production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01121253A true JPH01121253A (en) | 1989-05-12 |
Family
ID=17619703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28005787A Pending JPH01121253A (en) | 1987-11-05 | 1987-11-05 | Inclusion compound of ethanolamine derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01121253A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8765964B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
-
1987
- 1987-11-05 JP JP28005787A patent/JPH01121253A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8765964B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US8765963B2 (en) | 2009-09-01 | 2014-07-01 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE45261E1 (en) | 2009-09-01 | 2014-11-25 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE45275E1 (en) | 2009-09-01 | 2014-12-02 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US8940903B2 (en) | 2009-09-01 | 2015-01-27 | Catabasis Pharmaceuticals, Inc. | Niacin conjugated fatty acid mixtures and their uses |
| US9238077B2 (en) | 2009-09-01 | 2016-01-19 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US9278136B2 (en) | 2009-09-01 | 2016-03-08 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| US9486534B2 (en) | 2009-09-01 | 2016-11-08 | Catabasis Pharmaceuticals, Inc. | Niacin conjugated fatty acid mixtures and their uses |
| USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
| USRE46605E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
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