JPS60258119A

JPS60258119A - 高脂血症治療剤

高脂血症治療剤

Info

Publication number: JPS60258119A
Authority: JP; Japan
Prior art keywords: acid; cyclobranol; cycloartenol; acid ester; group
Prior art date: 1984-06-04
Legal status : Granted

Application number

JP59115307A

Other languages

English (en)

Japanese (ja)

Other versions

JPH0140014B2 (enExample

Inventor

Fumio Kuzutani

葛谷　文男

Goro Kimura

木村　午朗

Masanari Fujita

藤田　勝成

Yoshihiko Hirose

広瀬　芳彦

Current Assignee

Amano Enzyme Inc

Original Assignee

Amano Pharmaceutical Co Ltd

Priority date

1984-06-04

Filing date

1984-06-04

Publication date

1985-12-20

1984-06-04 Application filed by Amano Pharmaceutical Co Ltd filed Critical Amano Pharmaceutical Co Ltd

1984-06-04 Priority to JP59115307A priority Critical patent/JPS60258119A/ja

1985-05-17 Priority to CA000481808A priority patent/CA1265785A/en

1985-05-30 Priority to AU43130/85A priority patent/AU598724B2/en

1985-05-30 Priority to DE8585303839T priority patent/DE3579064D1/de

1985-05-30 Priority to US06/739,183 priority patent/US4748161A/en

1985-05-30 Priority to EP85303839A priority patent/EP0166542B1/en

1985-05-31 Priority to KR1019850003819A priority patent/KR920007235B1/ko

1985-06-03 Priority to DK246985A priority patent/DK246985A/da

1985-06-03 Priority to FI852216A priority patent/FI852216A7/fi

1985-06-03 Priority to NO85852246A priority patent/NO852246L/no

1985-06-04 Priority to ES544466A priority patent/ES8708125A1/es

1985-12-20 Publication of JPS60258119A publication Critical patent/JPS60258119A/ja

1989-08-24 Publication of JPH0140014B2 publication Critical patent/JPH0140014B2/ja

Status Granted legal-status Critical Current

Links

201000005577 familial hyperlipidemia Diseases 0.000 title abstract 2
-1 organic acid esters Chemical class 0.000 claims abstract description 130
CIBNJPPYSPYHDB-UHFFFAOYSA-N Cyclobranol Natural products C1CC(O)C(C)(C)C2C31CC13CCC3(C)C(C(CCC(C)=C(C)C)C)CCC3(C)C1CC2 CIBNJPPYSPYHDB-UHFFFAOYSA-N 0.000 claims abstract description 81
RRTBTJPVUGMUNR-UHFFFAOYSA-N Cycloartanol Natural products C12CCC(C(C(O)CC3)(C)C)C3C2(CC)CCC2(C)C1(C)CCC2C(C)CCCC(C)C RRTBTJPVUGMUNR-UHFFFAOYSA-N 0.000 claims abstract description 78
YNBJLDSWFGUFRT-UHFFFAOYSA-N cycloartenol Natural products CC(CCC=C(C)C)C1CCC2(C)C1(C)CCC34CC35CCC(O)C(C)(C)C5CCC24C YNBJLDSWFGUFRT-UHFFFAOYSA-N 0.000 claims abstract description 78
XZEUYTKSAYNYPK-UHFFFAOYSA-N 3beta-29-Norcycloart-24-en-3-ol Natural products C1CC2(C)C(C(CCC=C(C)C)C)CCC2(C)C2CCC3C(C)C(O)CCC33C21C3 XZEUYTKSAYNYPK-UHFFFAOYSA-N 0.000 claims abstract description 76
HVXLSFNCWWWDPA-UHFFFAOYSA-N Isocycloartenol Natural products C1CC(O)C(C)(C)C2C31CC13CCC3(C)C(C(CCCC(C)=C)C)CCC3(C)C1CC2 HVXLSFNCWWWDPA-UHFFFAOYSA-N 0.000 claims abstract description 76
HXQRIQXPGMPSRW-UHZRDUGNSA-N Pollinastanol Natural products O[C@@H]1C[C@H]2[C@@]3([C@]4([C@H]([C@@]5(C)[C@@](C)([C@H]([C@H](CCCC(C)C)C)CC5)CC4)CC2)C3)CC1 HXQRIQXPGMPSRW-UHZRDUGNSA-N 0.000 claims abstract description 76
FODTZLFLDFKIQH-UHFFFAOYSA-N cycloartenol trans-ferulate Natural products C1=C(O)C(OC)=CC(C=CC(=O)OC2C(C3CCC4C5(C)CCC(C5(C)CCC54CC53CC2)C(C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-UHFFFAOYSA-N 0.000 claims abstract description 76
CIBNJPPYSPYHDB-UEBIAWITSA-N cyclobranol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@@H](CCC(C)=C(C)C)C)CC[C@@]3(C)[C@@H]1CC2 CIBNJPPYSPYHDB-UEBIAWITSA-N 0.000 claims abstract description 73
ONQRKEUAIJMULO-YBXTVTTCSA-N cycloartenol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@@H](CCC=C(C)C)C)CC[C@@]3(C)[C@@H]1CC2 ONQRKEUAIJMULO-YBXTVTTCSA-N 0.000 claims abstract description 67
KKSCKZFKHNHGEO-UHFFFAOYSA-N 24-methylenecycloartanol Natural products CC(CCC(=C)C(C)(C)O)C1CCC2C3CCC4C(C)(C)C(O)CCC45CC35CCC12C KKSCKZFKHNHGEO-UHFFFAOYSA-N 0.000 claims abstract description 43
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 37
150000007524 organic acids Chemical class 0.000 claims abstract description 25
239000005711 Benzoic acid Substances 0.000 claims abstract description 19
235000010233 benzoic acid Nutrition 0.000 claims abstract description 19
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims abstract description 19
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims abstract description 17
235000013985 cinnamic acid Nutrition 0.000 claims abstract description 17
229930016911 cinnamic acid Natural products 0.000 claims abstract description 17
125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
150000001555 benzenes Chemical class 0.000 claims abstract description 16
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims abstract description 15
125000005157 alkyl carboxy group Chemical group 0.000 claims abstract description 14
150000002148 esters Chemical class 0.000 claims description 59
239000002253 acid Substances 0.000 claims description 52
BJZVHTWNCLKZGN-SPQNPFHSSA-N 24-methylidenecycloartanol Natural products CC(C)C(=C)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C(C)(C)[C@@H](O)CC[C@@]45C[C@@]35CC[C@]12C BJZVHTWNCLKZGN-SPQNPFHSSA-N 0.000 claims description 42
BDHQMRXFDYJGII-UEBIAWITSA-N 24-methylenecycloartanol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@H](C)CCC(=C)C(C)C)CC[C@@]3(C)[C@@H]1CC2 BDHQMRXFDYJGII-UEBIAWITSA-N 0.000 claims description 38
208000031226 Hyperlipidaemia Diseases 0.000 claims description 34
239000003814 drug Substances 0.000 claims description 33
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
229940124597 therapeutic agent Drugs 0.000 claims description 28
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 27
229960004050 aminobenzoic acid Drugs 0.000 claims description 21
239000011664 nicotinic acid Substances 0.000 claims description 17
229960003512 nicotinic acid Drugs 0.000 claims description 17
235000001968 nicotinic acid Nutrition 0.000 claims description 17
235000020778 linoleic acid Nutrition 0.000 claims description 14
OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims description 14
KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 claims description 13
KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 11
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 10
229940090248 4-hydroxybenzoic acid Drugs 0.000 claims description 9
NGSWKAQJJWESNS-UHFFFAOYSA-N 4-coumaric acid Chemical compound OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 claims description 8
YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 claims description 7
WTPDKEAYVAXNRO-UHFFFAOYSA-N 4-acetyloxy-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1OC(C)=O WTPDKEAYVAXNRO-UHFFFAOYSA-N 0.000 claims description 7
OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 claims description 7
OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 claims description 7
SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims description 6
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
KDTUPJQCNDBOJZ-UHFFFAOYSA-N 3-(4-acetyloxy-3-ethoxyphenyl)prop-2-enoic acid Chemical compound CCOC1=CC(C=CC(O)=O)=CC=C1OC(C)=O KDTUPJQCNDBOJZ-UHFFFAOYSA-N 0.000 claims description 5
QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 claims description 5
IHKNVZISLLDMOR-UHFFFAOYSA-N O-Acetylferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1OC(C)=O IHKNVZISLLDMOR-UHFFFAOYSA-N 0.000 claims description 5
IHKNVZISLLDMOR-GQCTYLIASA-N O-acetylferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1OC(C)=O IHKNVZISLLDMOR-GQCTYLIASA-N 0.000 claims description 5
ZWHTWBSYWXSZCD-GQCTYLIASA-N (e)-3-(3-ethoxy-4-hydroxyphenyl)prop-2-enoic acid Chemical compound CCOC1=CC(\C=C\C(O)=O)=CC=C1O ZWHTWBSYWXSZCD-GQCTYLIASA-N 0.000 claims description 4
NGMYCWFGNSXLMP-UHFFFAOYSA-N 3-acetyloxybenzoic acid Chemical compound CC(=O)OC1=CC=CC(C(O)=O)=C1 NGMYCWFGNSXLMP-UHFFFAOYSA-N 0.000 claims description 4
BYHBHNKBISXCEP-QPJJXVBHSA-N 4-acetoxycinnamic acid Chemical compound CC(=O)OC1=CC=C(\C=C\C(O)=O)C=C1 BYHBHNKBISXCEP-QPJJXVBHSA-N 0.000 claims description 4
ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 claims description 4
BYHBHNKBISXCEP-UHFFFAOYSA-N p-acetoxy-cinnamic acid Natural products CC(=O)OC1=CC=C(C=CC(O)=O)C=C1 BYHBHNKBISXCEP-UHFFFAOYSA-N 0.000 claims description 4
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
RBOMGDPEJGZFNE-UHFFFAOYSA-N 3-(3-methoxy-4-propanoyloxyphenyl)prop-2-enoic acid Chemical compound CCC(=O)OC1=CC=C(C=CC(O)=O)C=C1OC RBOMGDPEJGZFNE-UHFFFAOYSA-N 0.000 claims description 3
QFDSMZGWVHEDHT-UHFFFAOYSA-N 3-ethoxy-4-hydroxybenzoic acid Chemical compound CCOC1=CC(C(O)=O)=CC=C1O QFDSMZGWVHEDHT-UHFFFAOYSA-N 0.000 claims description 3
AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 claims description 3
MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 claims description 3
GDBUZIKSJGRBJP-UHFFFAOYSA-N 4-acetoxy benzoic acid Chemical compound CC(=O)OC1=CC=C(C(O)=O)C=C1 GDBUZIKSJGRBJP-UHFFFAOYSA-N 0.000 claims description 3
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 claims description 3
TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 claims description 3
ZDIYGBWFISUTHI-GQCTYLIASA-N (e)-3-(3,4-diacetyloxyphenyl)prop-2-enoic acid Chemical compound CC(=O)OC1=CC=C(\C=C\C(O)=O)C=C1OC(C)=O ZDIYGBWFISUTHI-GQCTYLIASA-N 0.000 claims description 2
WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 claims description 2
DNUYOWCKBJFOGS-UHFFFAOYSA-N 2-[[10-(2,2-dicarboxyethyl)anthracen-9-yl]methyl]propanedioic acid Chemical compound C1=CC=C2C(CC(C(=O)O)C(O)=O)=C(C=CC=C3)C3=C(CC(C(O)=O)C(O)=O)C2=C1 DNUYOWCKBJFOGS-UHFFFAOYSA-N 0.000 claims description 2
DAUAQNGYDSHRET-UHFFFAOYSA-N 3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OC DAUAQNGYDSHRET-UHFFFAOYSA-N 0.000 claims description 2
DTFQMPQJMDEWKJ-UHFFFAOYSA-N 3-ethoxybenzoic acid Chemical compound CCOC1=CC=CC(C(O)=O)=C1 DTFQMPQJMDEWKJ-UHFFFAOYSA-N 0.000 claims description 2
GPVDHNVGGIAOQT-UHFFFAOYSA-N Veratric acid Natural products COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
IJFXRHURBJZNAO-UHFFFAOYSA-N meta--hydroxybenzoic acid Natural products OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 claims description 2
FJVSTYFZOUSZCS-UHFFFAOYSA-N 3,4-diacetyloxybenzoic acid Chemical compound CC(=O)OC1=CC=C(C(O)=O)C=C1OC(C)=O FJVSTYFZOUSZCS-UHFFFAOYSA-N 0.000 claims 2
150000001875 compounds Chemical class 0.000 abstract description 128
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 60
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](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 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 47
210000002966 serum Anatomy 0.000 abstract description 26
235000012000 cholesterol Nutrition 0.000 abstract description 21
108010023302 HDL Cholesterol Proteins 0.000 abstract description 17
FODTZLFLDFKIQH-FSVGXZBPSA-N gamma-Oryzanol (TN) Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)O[C@@H]2C([C@@H]3CC[C@H]4[C@]5(C)CC[C@@H]([C@@]5(C)CC[C@@]54C[C@@]53CC2)[C@H](C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-FSVGXZBPSA-N 0.000 abstract description 14
150000003648 triterpenes Chemical class 0.000 abstract description 9
235000005985 organic acids Nutrition 0.000 abstract description 8
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract description 4
150000003904 phospholipids Chemical class 0.000 abstract description 2
239000000470 constituent Substances 0.000 abstract 1
150000002895 organic esters Chemical class 0.000 abstract 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 296
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 122
238000006243 chemical reaction Methods 0.000 description 111
238000002844 melting Methods 0.000 description 99
230000008018 melting Effects 0.000 description 99
238000000921 elemental analysis Methods 0.000 description 93
239000000203 mixture Substances 0.000 description 91
239000002904 solvent Substances 0.000 description 89
238000000034 method Methods 0.000 description 83
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 82
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 79
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
238000002360 preparation method Methods 0.000 description 65
239000000243 solution Substances 0.000 description 63
238000004519 manufacturing process Methods 0.000 description 51
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
239000013078 crystal Substances 0.000 description 38
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 37
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238000010898 silica gel chromatography Methods 0.000 description 35
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 30
239000008187 granular material Substances 0.000 description 29
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
238000001035 drying Methods 0.000 description 21
229920000168 Microcrystalline cellulose Polymers 0.000 description 20
239000008108 microcrystalline cellulose Substances 0.000 description 20
229940016286 microcrystalline cellulose Drugs 0.000 description 20
235000019813 microcrystalline cellulose Nutrition 0.000 description 20
230000003287 optical effect Effects 0.000 description 20
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
235000011114 ammonium hydroxide Nutrition 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
229920002261 Corn starch Polymers 0.000 description 17
239000008120 corn starch Substances 0.000 description 17
229940099112 cornstarch Drugs 0.000 description 17
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 15
230000003247 decreasing effect Effects 0.000 description 15
230000000694 effects Effects 0.000 description 15
235000019359 magnesium stearate Nutrition 0.000 description 15
238000005259 measurement Methods 0.000 description 15
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 14
239000002775 capsule Substances 0.000 description 13
229960004232 linoleic acid Drugs 0.000 description 13
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