CN100540523C - L-2-(Alpha-hydroxy amyl group) benzoate and method for making and purposes - Google Patents
L-2-(Alpha-hydroxy amyl group) benzoate and method for making and purposes Download PDFInfo
- Publication number
- CN100540523C CN100540523C CNB2004100482689A CN200410048268A CN100540523C CN 100540523 C CN100540523 C CN 100540523C CN B2004100482689 A CNB2004100482689 A CN B2004100482689A CN 200410048268 A CN200410048268 A CN 200410048268A CN 100540523 C CN100540523 C CN 100540523C
- Authority
- CN
- China
- Prior art keywords
- alpha
- amyl group
- hydroxy amyl
- benzoate
- hydroxy
- 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.)
- Expired - Lifetime
Links
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 title claims abstract description 80
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 36
- 230000002490 cerebral effect Effects 0.000 claims abstract description 12
- 230000000302 ischemic effect Effects 0.000 claims abstract description 12
- 210000004556 brain Anatomy 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 11
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 9
- 230000002785 anti-thrombosis Effects 0.000 claims abstract description 8
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 208000019553 vascular disease Diseases 0.000 claims abstract description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 229950005197 butylphthalide Drugs 0.000 claims description 31
- 238000003756 stirring Methods 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 17
- 206010008118 cerebral infarction Diseases 0.000 claims description 14
- 229910021645 metal ion Inorganic materials 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
- 239000002798 polar solvent Substances 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 238000010253 intravenous injection Methods 0.000 claims description 10
- -1 metallic ion salt Chemical class 0.000 claims description 10
- 150000001455 metallic ions Chemical class 0.000 claims description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 229910052791 calcium Inorganic materials 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 229910052700 potassium Inorganic materials 0.000 claims description 7
- 239000011591 potassium Substances 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims 1
- 125000001033 ether group Chemical group 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 33
- 230000002265 prevention Effects 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 39
- 239000001103 potassium chloride Substances 0.000 description 39
- 235000011164 potassium chloride Nutrition 0.000 description 39
- 241000700159 Rattus Species 0.000 description 36
- 159000000007 calcium salts Chemical class 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 229940050390 benzoate Drugs 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- 208000007536 Thrombosis Diseases 0.000 description 18
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- SVDVJBWDBYSQLO-UHFFFAOYSA-N 5-(4-hydroxy-3-methoxyphenyl)-5-phenylimidazolidine-2,4-dione Chemical compound C1=C(O)C(OC)=CC(C2(C(NC(=O)N2)=O)C=2C=CC=CC=2)=C1 SVDVJBWDBYSQLO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 101000937642 Homo sapiens Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Proteins 0.000 description 12
- 102100027329 Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Human genes 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 208000026106 cerebrovascular disease Diseases 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 230000009102 absorption Effects 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 229940032147 starch Drugs 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 210000003194 forelimb Anatomy 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007574 infarction Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 4
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 3
- 240000008415 Lactuca sativa Species 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 3
- 238000011047 acute toxicity test Methods 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000004731 jugular vein Anatomy 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000000452 restraining effect Effects 0.000 description 3
- 235000012045 salad Nutrition 0.000 description 3
- XYGBKMMCQDZQOZ-UHFFFAOYSA-M sodium;4-hydroxybutanoate Chemical compound [Na+].OCCCC([O-])=O XYGBKMMCQDZQOZ-UHFFFAOYSA-M 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
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- 239000008215 water for injection Substances 0.000 description 3
- 235000020985 whole grains Nutrition 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- HJXMNVQARNZTEE-UHFFFAOYSA-N Butylphthalide Chemical compound C1=CC=C2C(CCCC)OC(=O)C2=C1 HJXMNVQARNZTEE-UHFFFAOYSA-N 0.000 description 2
- 241000272165 Charadriidae Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
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- 150000001555 benzenes Chemical class 0.000 description 2
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- 210000001168 carotid artery common Anatomy 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
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- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
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- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 2
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- 235000010235 potassium benzoate Nutrition 0.000 description 2
- 239000004300 potassium benzoate Substances 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
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- 150000003751 zinc Chemical class 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N Benzyl benzoate Natural products C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- VNISHQVQKIEFLS-UHFFFAOYSA-N C(C1=CC=CC=C1)NCCNCC1=CC=CC=C1.C1(=CC=CC=C1)C(=O)O Chemical compound C(C1=CC=CC=C1)NCCNCC1=CC=CC=C1.C1(=CC=CC=C1)C(=O)O VNISHQVQKIEFLS-UHFFFAOYSA-N 0.000 description 1
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- 206010008092 Cerebral artery thrombosis Diseases 0.000 description 1
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- 208000027418 Wounds and injury Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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- MAVQEIXZEBBKHE-UHFFFAOYSA-N benzoic acid;2-methylpropan-2-amine Chemical compound CC(C)(C)N.OC(=O)C1=CC=CC=C1 MAVQEIXZEBBKHE-UHFFFAOYSA-N 0.000 description 1
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- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- LDJNSLOKTFFLSL-UHFFFAOYSA-M lithium;benzoate Chemical compound [Li+].[O-]C(=O)C1=CC=CC=C1 LDJNSLOKTFFLSL-UHFFFAOYSA-M 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- PJJZFXPJNUVBMR-UHFFFAOYSA-L magnesium benzoate Chemical class [Mg+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 PJJZFXPJNUVBMR-UHFFFAOYSA-L 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical class C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- SCZVXVGZMZRGRU-UHFFFAOYSA-N n'-ethylethane-1,2-diamine Chemical compound CCNCCN SCZVXVGZMZRGRU-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- SBNFWQZLDJGRLK-UHFFFAOYSA-N phenothrin Chemical compound CC1(C)C(C=C(C)C)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 SBNFWQZLDJGRLK-UHFFFAOYSA-N 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 210000003582 temporal bone Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- JDLYKQWJXAQNNS-UHFFFAOYSA-L zinc;dibenzoate Chemical compound [Zn+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 JDLYKQWJXAQNNS-UHFFFAOYSA-L 0.000 description 1
- 210000000216 zygoma Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
C | H | |
Theoretical value % | 58.51 | 6.14 |
Measured value % | 58.60 | 6.10 |
C | H | |
Theoretical value % | 63.41 | 6.65 |
Measured value % | 63.50 | 6.61 |
C | H | N | |
Theoretical value % | 73.14 | 7.98 | 4.26 |
Measured value % | 73.09 | 8.03 | 4.22 |
C | H | N | |
Theoretical value % | 68.29 | 9.67 | 4.98 |
Measured value % | 68.33 | 9.65 | 4.95 |
C | H | N | |
Theoretical value % | 72.35 | 7.99 | 4.44 |
Measured value % | 72.40 | 7.95 | 4.50 |
Composition | Quantity (mg/ sheet) |
L-2-(Alpha-hydroxy amyl group) benzoate | 100 |
Starch | 50 |
Microcrystalline Cellulose | 35 |
Magnesium Stearate | 2 |
Xylo-Mucine | 5 |
Composition | Quantity (mg/ capsule) |
L-2-(Alpha-hydroxy amyl group) benzoate | 100 |
Starch | 50 |
Xylo-Mucine | 3 |
Commissure PVP | 1 |
Magnesium Stearate | 1.5 |
Composition | Quantity (mg/ bag) |
L-2-(Alpha-hydroxy amyl group) benzoate | 100 |
Starch | 1000 |
Dextrin | 150 |
Icing Sugar | 150 |
Composition | Quantity |
L-2-(Alpha-hydroxy amyl group) benzoate | The 100mg/ bottle |
Sodium hydroxide | In right amount |
Water for injection | In right amount |
Sodium-chlor | In right amount |
Composition | Quantity |
L-2-(Alpha-hydroxy amyl group) benzoate | The 100mg/ bottle |
Sodium hydroxide | In right amount |
N.F,USP MANNITOL | In right amount |
Claims (8)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2004100482689A CN100540523C (en) | 2004-06-17 | 2004-06-17 | L-2-(Alpha-hydroxy amyl group) benzoate and method for making and purposes |
PCT/CN2005/000102 WO2005123651A1 (en) | 2004-06-17 | 2005-01-24 | L-2-(α-HYDROXYPENTYL)BENZOATES, THE PREPARATION AND THE USE THEREOF |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2004100482689A CN100540523C (en) | 2004-06-17 | 2004-06-17 | L-2-(Alpha-hydroxy amyl group) benzoate and method for making and purposes |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1594270A CN1594270A (en) | 2005-03-16 |
CN100540523C true CN100540523C (en) | 2009-09-16 |
Family
ID=34665740
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2004100482689A Expired - Lifetime CN100540523C (en) | 2004-06-17 | 2004-06-17 | L-2-(Alpha-hydroxy amyl group) benzoate and method for making and purposes |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN100540523C (en) |
WO (1) | WO2005123651A1 (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010003287A1 (en) * | 2008-07-08 | 2010-01-14 | 中国医学科学院药物研究所 | THE USE OF POTASSIUM 2-(α- HYDROXYPENTYL) BENZOATE IN THE MANUFACTURE OF MEDICAMENTS FOR PREVENTING AND/OR TREATING SENILE DEMENTIA |
CN101402565B (en) * | 2008-11-14 | 2012-07-04 | 郑州大学 | Halogenated 2-(a-hydroxyl pentyl) benzoate, production method and uses thereof |
CN103113210A (en) * | 2013-02-19 | 2013-05-22 | 石药集团中奇制药技术(石家庄)有限公司 | Hydroxyl amyl benzoate potassium crystal and preparation method thereof |
CN103127025B (en) * | 2013-03-06 | 2016-03-09 | 石家庄鸯星科技有限公司 | The preparation method of racemization 2-(Alpha-hydroxy amyl group) benzoate sheet |
CN105343014B (en) * | 2013-03-25 | 2018-08-24 | 贵州贵安新区协生元医药科技有限公司 | Injection racemization 2- (Alpha-hydroxy amyl) benzoate freeze-dried powder and preparation method thereof |
CN104086399B (en) | 2013-07-17 | 2016-08-24 | 浙江奥翔药业股份有限公司 | 5-bromo-2-(Alpha-hydroxy amyl group) different crystal forms and preparation method thereof of benzoic acid sodium salt |
ES2927538T3 (en) * | 2018-03-19 | 2022-11-08 | Henan Genuine Biotech Co Ltd | Benzoic acid compounds and preparation method thereof and applications thereof |
CN116262698A (en) * | 2023-03-22 | 2023-06-16 | 成都施贝康生物医药科技有限公司 | Novel 2- (1-hydroxypentyl) benzoic acid naphthenamine salt |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1136209C (en) * | 1999-07-05 | 2004-01-28 | 中国医学科学院药物研究所 | Process for preparing optically active 3-n-butyl phenylphthaleine |
CN1243541C (en) * | 2002-05-09 | 2006-03-01 | 中国医学科学院药物研究所 | 2-(alpha-hydroxypentyl) benzoate and its preparing process and usage |
-
2004
- 2004-06-17 CN CNB2004100482689A patent/CN100540523C/en not_active Expired - Lifetime
-
2005
- 2005-01-24 WO PCT/CN2005/000102 patent/WO2005123651A1/en active Application Filing
Also Published As
Publication number | Publication date |
---|---|
CN1594270A (en) | 2005-03-16 |
WO2005123651A8 (en) | 2006-04-13 |
WO2005123651A1 (en) | 2005-12-29 |
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