CN105481772B - 一种奥扎格雷钠晶型化合物 - Google Patents
一种奥扎格雷钠晶型化合物 Download PDFInfo
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- CN105481772B CN105481772B CN201610075581.4A CN201610075581A CN105481772B CN 105481772 B CN105481772 B CN 105481772B CN 201610075581 A CN201610075581 A CN 201610075581A CN 105481772 B CN105481772 B CN 105481772B
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- ozagrel
- sodium
- sodium ozagrel
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- SHZKQBHERIJWAO-AATRIKPKSA-N ozagrel Chemical compound C1=CC(/C=C/C(=O)O)=CC=C1CN1C=NC=C1 SHZKQBHERIJWAO-AATRIKPKSA-N 0.000 title claims abstract description 58
- 229950003837 ozagrel Drugs 0.000 title claims abstract description 57
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 230000005260 alpha ray Effects 0.000 claims abstract description 6
- 238000005259 measurement Methods 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 12
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- 238000002360 preparation method Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 238000001228 spectrum Methods 0.000 claims description 6
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- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 229910017488 Cu K Inorganic materials 0.000 claims description 5
- 229910017541 Cu-K Inorganic materials 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 206010067347 Thrombotic cerebral infarction Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
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- 230000000052 comparative effect Effects 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 14
- 239000013078 crystal Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 9
- 208000007536 Thrombosis Diseases 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000011282 treatment Methods 0.000 description 5
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- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 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 description 3
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 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 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
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- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
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- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
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- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
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- 101800003906 Substance P Proteins 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
- 206010044541 Traumatic shock Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- 201000007201 aphasia Diseases 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
- 201000010099 disease Diseases 0.000 description 1
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- 210000001259 mesencephalon Anatomy 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
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- XNRNNGPBEPRNAR-JQBLCGNGSA-N thromboxane B2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1OC(O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O XNRNNGPBEPRNAR-JQBLCGNGSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- 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
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
序号 | 衍射角2θ(度) | d值 | 相对强度(%) |
1 | 4.823 | 18.30799 | 1.9 |
2 | 6.381 | 13.84009 | 3.1 |
3 | 8.377 | 10.5463 | 1.6 |
4 | 8.81 | 10.02902 | 3.8 |
5 | 9.168 | 9.63796 | 40.1 |
6 | 9.611 | 9.1955 | 4.8 |
7 | 11.394 | 7.76016 | 28.8 |
8 | 11.715 | 7.54776 | 28.7 |
9 | 11.996 | 7.37163 | 19.5 |
10 | 12.738 | 6.9438 | 4 |
11 | 13.393 | 6.60555 | 1.2 |
12 | 14.527 | 6.09242 | 15 |
13 | 15.245 | 5.80723 | 100 |
14 | 15.896 | 5.57098 | 36 |
15 | 16.534 | 5.35718 | 23.9 |
16 | 17.02 | 5.20529 | 94.3 |
17 | 17.412 | 5.08904 | 85.8 |
18 | 18.061 | 4.90755 | 16.8 |
19 | 18.652 | 4.75343 | 10.4 |
20 | 19.065 | 4.65136 | 83.4 |
21 | 20.459 | 4.33752 | 19.7 |
22 | 21.075 | 4.212 | 11.9 |
23 | 21.583 | 4.11405 | 6.3 |
24 | 22.088 | 4.02112 | 2.6 |
25 | 22.876 | 3.88445 | 12.1 |
26 | 23.634 | 3.76144 | 20.2 |
27 | 23.88 | 3.72334 | 33.9 |
28 | 24.333 | 3.65499 | 46.4 |
29 | 24.747 | 3.59481 | 11.8 |
30 | 25.512 | 3.48863 | 3.5 |
31 | 25.887 | 3.43904 | 3.5 |
32 | 26.113 | 3.40978 | 2.7 |
33 | 26.545 | 3.35519 | 8.9 |
34 | 27.127 | 3.28455 | 4.6 |
35 | 27.518 | 3.23872 | 4.9 |
36 | 27.83 | 3.2032 | 3 |
37 | 28.196 | 3.16238 | 2.6 |
38 | 28.813 | 3.09607 | 3.1 |
39 | 29.246 | 3.05123 | 5.2 |
40 | 30.817 | 2.89917 | 3.1 |
41 | 31.752 | 2.81587 | 3.2 |
42 | 32.071 | 2.78858 | 2 |
43 | 32.631 | 2.742 | 7.4 |
44 | 33.424 | 2.67872 | 7.9 |
45 | 33.793 | 2.65034 | 2.7 |
46 | 34.33 | 2.61007 | 3.2 |
47 | 34.938 | 2.56606 | 5.2 |
48 | 35.85 | 2.50285 | 2.3 |
49 | 36.417 | 2.46516 | 2.1 |
50 | 37.294 | 2.4092 | 2.4 |
51 | 37.999 | 2.36607 | 3.4 |
52 | 38.756 | 2.32157 | 2.2 |
参数 | 实施例1 | 对比例1 | 对比例2 | 对比例3 | 对比例4 | 对比例5 |
Cmax /mg·L−1 | 47.91±11.24 | 35.54±12.47 | 32.69±14.25 | 29.15±8.76 | 37.19±15.20 | 32.51±9.27 |
tmax /h | 0.89±0.31 | 1.29±0.51 | 1.04±0.17 | 0.62±0.27 | 1.09±0.34 | 0.74±0.60 |
AUC0−t /mg·L−1·h | 92.42±13.60 | 65.25±10.10 | 61.38±14.04 | 54.11±9.78 | 62.32±11.73 | 72.69±13.81 |
t1/2 /h | 3.69±0.42 | 1.19±0.64 | 2.54±0.47 | 1.37±0.75 | 1.84±0.77 | 1.02±0.51 |
Claims (4)
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101397272A (zh) * | 2008-07-21 | 2009-04-01 | 海南碧凯药业有限公司 | 制备奥扎格雷钠结晶的方法 |
CN102408375A (zh) * | 2011-11-03 | 2012-04-11 | 天津市汉康医药生物技术有限公司 | 奥扎格雷钠化合物 |
CN103044333A (zh) * | 2013-01-11 | 2013-04-17 | 德州翰华医药化学有限公司 | 一种高纯度奥扎格雷钠的制备方法 |
CN103232395A (zh) * | 2013-05-03 | 2013-08-07 | 四川省惠达药业有限公司 | 一种奥扎格雷钠的化合物、其制备方法及其药物组合物 |
CN105267162A (zh) * | 2015-11-29 | 2016-01-27 | 南京多宝生物科技有限公司 | 一种治疗脑梗塞的注射用奥扎格雷钠冻干粉 |
-
2016
- 2016-02-03 CN CN201610075581.4A patent/CN105481772B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101397272A (zh) * | 2008-07-21 | 2009-04-01 | 海南碧凯药业有限公司 | 制备奥扎格雷钠结晶的方法 |
CN102408375A (zh) * | 2011-11-03 | 2012-04-11 | 天津市汉康医药生物技术有限公司 | 奥扎格雷钠化合物 |
CN103044333A (zh) * | 2013-01-11 | 2013-04-17 | 德州翰华医药化学有限公司 | 一种高纯度奥扎格雷钠的制备方法 |
CN103232395A (zh) * | 2013-05-03 | 2013-08-07 | 四川省惠达药业有限公司 | 一种奥扎格雷钠的化合物、其制备方法及其药物组合物 |
CN105267162A (zh) * | 2015-11-29 | 2016-01-27 | 南京多宝生物科技有限公司 | 一种治疗脑梗塞的注射用奥扎格雷钠冻干粉 |
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