CN1249686A - 帕罗西丁制剂 - Google Patents
帕罗西丁制剂 Download PDFInfo
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- CN1249686A CN1249686A CN98803170A CN98803170A CN1249686A CN 1249686 A CN1249686 A CN 1249686A CN 98803170 A CN98803170 A CN 98803170A CN 98803170 A CN98803170 A CN 98803170A CN 1249686 A CN1249686 A CN 1249686A
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- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 44
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 title claims abstract description 42
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 42
- 239000000203 mixture Substances 0.000 title claims abstract description 10
- 238000001694 spray drying Methods 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims abstract description 9
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000003449 preventive effect Effects 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 238000009472 formulation Methods 0.000 abstract 1
- 229960005183 paroxetine hydrochloride Drugs 0.000 abstract 1
- 239000008187 granular material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 206010029897 Obsessive thoughts Diseases 0.000 description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- CSMKKXOBOPQKGZ-UHFFFAOYSA-N [O].C1=CC=C2OCOC2=C1 Chemical compound [O].C1=CC=C2OCOC2=C1 CSMKKXOBOPQKGZ-UHFFFAOYSA-N 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
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- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 208000002271 trichotillomania Diseases 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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Abstract
通过喷雾干燥帕罗西丁盐酸盐的半水合物或其它无水物/水合物/溶剂化物/无定形形式的溶液,以得到自由流动和易溶解形式的帕罗西丁盐酸盐(适于制备固体制剂或适于不经肠胃使用的)水溶液。
Description
本发明涉及药用活性的化合物的制备方法，及所制备的化合物在治疗方面的应用。本发明特别涉及帕罗西丁(paroxetine)盐酸盐自由流动的形式的制备。
具有抗抑郁和抗帕金森氏病功能的药品，在US-A-3912743和US-A-4007196已有介绍。这些论述中尤为重要的一种化合物是帕罗西丁，4-(4′-氟代苯基)-3′，4′-(亚甲基二氧苯氧基甲基)-哌啶的反式异构体。所述化合物以盐酸盐形式特别用于治疗抑郁症、强迫性障碍(OCD)和恐慌症。
在文献中，帕罗西丁盐酸盐被描述为晶状半水合物(参见BeechamGroup的EP-A-0223403)和各种晶状的无水形式(参见SmithKlineBeecham plc的WO96/24595)。这些已知的形式所具有的性质对于所有的制药应用来说是不理想的，并且，它们要经多步方法制备，包括需小心控制条件的析出、过滤、干燥和均化等。较好的结晶过程使用有机溶剂，它比水成本更高、且会带来安全与环境的问题。进一步地，用均匀、规则的粒度制备晶体产品的困难带来了制剂的包胶囊的问题。晶体产品的流动性质限止了大量的传送和制剂技术的选择应用，同时灰尘的形成和静电性质是有害的。另外，已知的帕罗西丁盐酸盐固体形式是相对不溶的，要很久才能完全溶解。
这就需要具有改进加工和配制特性的帕罗西丁盐酸盐形式。
根据本发明的第一方面，它提供了制备自由流动形式的帕罗西丁盐酸盐的方法，它包括喷雾干燥帕罗西丁盐酸盐溶液。
喷雾干燥的原料可以方便地通过例如使帕罗西丁游离碱溶解于盐酸水溶液中制得，尽管帕罗西丁盐酸盐的其它固体形式也可以溶解。例如，通过溶解无定形的帕罗西丁盐酸盐或晶状的的帕罗西丁盐酸盐无水物、水合物或合适溶剂的溶剂化物来制得原料。所用的溶剂可以是纯净水或一种水与可溶混的有机溶剂的混合物。适用的可混溶的有机溶剂包括吡啶(pyridinem)乙酸、乙腈、丙酮、乙醇、丙-1-醇、丁-1-醇和四氢呋喃。或也可以用一合适的有机溶剂单独与帕罗西丁盐酸盐形成一种溶液。可用稍稍加热来达到及维持完全溶解，尽管一旦溶解且在无晶种存在的情况下，含水溶液在室温下可以稳定许多天。帕罗西丁盐酸盐的适于喷雾干燥的浓度范围为1-30％(重量)，优选5-20％(重量)。
在通常条件下，采用常规的喷雾干燥方法常常产生粘性的帕罗西丁盐酸盐颗粒，它们附着在仪器的表面且互相粘在一起。然而，当选择合适的仪器和操作条件以保证颗粒在撞击仪器壁之前充分冷却时，可成功地完成喷雾干燥。需要小心地控制喷嘴的液滴大小、气流的速度和温度以与所采用的仪器相适应。
上述工艺的帕罗西丁产品是自由流动的，是快湿及速溶的。高浓度溶液的制备不需要加热。
因此，本发明的第二个方面是喷雾干燥帕罗西丁盐酸盐。
发现本发明中喷雾干燥的帕罗西丁盐酸盐特别适合于以均匀的颗粒大小和良好的流动性质作为优点的应用当中。再者，因为在喷雾干燥中尽可能严密地控制颗粒的大小，所以所述产品可方便、安全地进行处理，而没有常规制备帕罗西丁盐酸盐固体时所产生的灰尘有关的危害。均匀的颗粒大小为优点的实施例包括控释和微胶囊化(颗粒的包衣技术)。用特殊用途的颗粒大小比如10-1000微米范围的颗粒，可以制备样品。
微胶囊化可以与所述的喷雾干燥工艺相结合，或在后续步骤中采用。这种工艺可用于掩蔽味道、及用于快释或控释制剂中、以及包括与组合产品的药物动力学性质相配的药物动力学的控制。
只用一个工艺步骤从原料溶液中分离出固体产品是可能的。因此，一般说来，不需要混合、制粒或干燥，尽管如果需要，可以增加一个额外的干燥步骤。如果采用含水原料，可完全避免通常与有机溶剂有关的成本和环境问题。
本发明的喷雾干燥产品可以在EP-A-0223403或WO96/24595中描述的剂型进行配制而用于治疗。自由流动性质有利于固体制剂的制备。而且，喷雾干燥的帕罗西丁盐酸盐的易溶性质使它适于制备不经肠使用的溶液。
本发明所述帕罗西丁产品在治疗方面的应用包括治疗酒精中毒、焦虑、忧郁、强迫性障碍、恐慌症、慢性疼痛、肥胖症、老年痴呆、偏头痛、易饿病、厌食症、社交恐怖症、经前综合征(PMS)、青春期抑郁症、trichotillomania、精神抑郁症和药物滥用，以下指“所述疾病”。
因此，本发明也提供：
为治疗或预防所述疾病的药用组合物，其包括喷雾干燥的帕罗西丁盐酸盐和药学上可接受的载体或可重新配制的喷雾干燥帕罗西丁盐酸盐的水溶液；
喷雾干燥的帕罗西丁盐酸盐用于制备固体或重新配制的液体形式的药物，该药物用以治疗或预防上述疾病；
治疗上述疾病的方法，其包括：对于患有一种或多种上述疾病的病人，给予为固体口服组合物或为口服或不经胃肠的组合物的有效治疗或预防量的帕罗西丁盐酸盐。
本发明通过下列实施例来说明。
实施例
在下列条件下，对10％的帕罗西丁盐酸盐水进行喷雾干燥：
仪器： Niro Fielder Mobile Minor
入口温度设定： 185℃
实际入口温度： 184℃-185℃
出口温度： 94℃-95℃
喷雾速度： 40,000-50,000rpm
泵速(蠕动泵)： 32-34rpm
空气供给 4.8-5.2巴
经过滤器的压差(DP)：
过滤袋： 流过起始57毫米水柱
流过结束65毫米水柱
Hepa过渡器： 流过起始7毫米水柱
流过结束7毫米水柱
经过孔板的压差： 流过起始80+毫米水柱
流过结束80+毫米水柱
Claims (12)
1.帕罗西丁盐酸盐自由流动形式的制备方法，它包括对帕罗西丁盐酸盐溶液的喷雾干燥。
2.根据权利要求1的方法，其中所述的喷雾干燥的原料是通过使帕罗西丁游离碱溶解于盐酸水溶液中来制备的。
3.根据权利要求1的方法，其中所述的原料是通过使无定形的帕罗西丁盐酸盐或晶状帕罗西丁盐酸盐的无水物、水合物或溶剂化物溶于合适的溶剂中来制备的。
4.根据权利要求1、2或3的方法，其中所述的溶剂是纯净水或水与一种或多种相容的有机溶剂的混合物。
5.根据权利要求1或3的方法，其中所述的帕罗西丁盐酸盐的溶解是无水情况下在合适有机溶剂中进行的。
6.根据权利要求4或5的方法，其中所述的有机溶剂选自吡啶、乙酸、乙腈、丙酮、乙醇、丙-1-醇、丁-1-醇和四氢呋喃。
7.根据前述任一项权利要求的方法，其中所述的帕罗西丁盐酸盐浓度在5％-20％(重量)之间。
8.喷雾干燥的帕罗西丁盐酸盐。
9.一种治疗和预防所述疾病的药用组合物，其包含，喷雾干燥的帕罗西丁盐酸盐和药学上可接受的载体或可重新配制的喷雾干燥的帕罗西丁盐酸盐的水溶液。
10.喷雾干燥的帕罗西丁盐酸盐用于制备固体或可重新配制的液体形式的药物以治疗或预防所述疾病。
11.治疗所述疾病的方法，其包括对患有一种或多种所述疾病的病人，给予有效或预防量的喷雾干燥的帕罗西丁盐酸盐，所述帕罗西丁盐酸盐是作为固体口服组合物或作为可重新配制的含水的口服的或不经肠胃的组合物给予的。
12.根据权利要求9的组合物、权利要求10的用途或权利要求11的方法，其中所述的喷雾干燥帕罗西丁盐酸盐是权利要求1至7任一项要求保护的方法的所述产品。
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9700692.8 | 1997-01-15 | ||
| GBGB9700692.8A GB9700692D0 (en) | 1997-01-15 | 1997-01-15 | Novel process and compound |
| GBGB9714873.8A GB9714873D0 (en) | 1997-07-15 | 1997-07-15 | Novel process and compound |
| GB9714873.8 | 1997-07-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1249686A true CN1249686A (zh) | 2000-04-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98803170A Pending CN1249686A (zh) | 1997-01-15 | 1998-01-12 | 帕罗西丁制剂 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US20010049442A1 (zh) |
| EP (1) | EP0952831A1 (zh) |
| JP (1) | JP2001508460A (zh) |
| KR (1) | KR20000070151A (zh) |
| CN (1) | CN1249686A (zh) |
| AP (1) | AP9901604A0 (zh) |
| AU (1) | AU730532B2 (zh) |
| BG (1) | BG103648A (zh) |
| BR (1) | BR9806754A (zh) |
| CA (1) | CA2277480A1 (zh) |
| EA (1) | EA002034B1 (zh) |
| HU (1) | HUP0000960A3 (zh) |
| ID (1) | ID23250A (zh) |
| IL (1) | IL130856A (zh) |
| NO (1) | NO993460L (zh) |
| NZ (1) | NZ336587A (zh) |
| OA (1) | OA11077A (zh) |
| PL (1) | PL334568A1 (zh) |
| SK (1) | SK95099A3 (zh) |
| TR (1) | TR199901622T2 (zh) |
| WO (1) | WO1998031365A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104027306A (zh) * | 2014-06-25 | 2014-09-10 | 万特制药(海南)有限公司 | 帕罗西汀口服混悬液及其制备方法 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9724544D0 (en) * | 1997-11-21 | 1998-01-21 | Smithkline Beecham Plc | Novel Formulation |
| US6168805B1 (en) * | 1998-05-07 | 2001-01-02 | Endo Pharmaceuticals, Inc. | Aqueous process for manufacturing paroxetine solid dispersions |
| GB9810181D0 (en) * | 1998-05-13 | 1998-07-08 | Smithkline Beecham Plc | Novel formulations |
| PT1100796E (pt) * | 1998-08-07 | 2003-09-30 | Smithkline Beecham Plc | Processo para a preparacao de um cloridrato de paroxetina na forma anidra nao cristalina |
| GB9824298D0 (en) * | 1998-11-05 | 1998-12-30 | Smithkline Beecham Plc | Novel process |
| EP1161241B1 (de) | 1999-03-12 | 2005-12-07 | Aesica Pharmaceuticals Ltd. | Stabile pharmazeutische anwendungsform für paroxetin-anhydrat |
| GB9914600D0 (en) * | 1999-06-22 | 1999-08-25 | Smithkline Beecham Plc | Novel,process |
| ES2162560B1 (es) * | 1999-06-25 | 2002-07-16 | Rodriguez Concepcion Pena | Uso de fluoxetina, paroxetina y otros isrs para la fabricacion de medicamentos con el fin de aumentar la capacidad de abstenerse de substancias o actividades que crean dependencia. |
| ATE248165T1 (de) | 1999-07-01 | 2003-09-15 | Italfarmaco Spa | Komplexe von paroxetin mit cyclodextrin oder cyclodextrin derivaten |
| GB9919052D0 (en) * | 1999-08-12 | 1999-10-13 | Smithkline Beecham Plc | Novel compound composition and process |
| GB9923439D0 (en) * | 1999-10-04 | 1999-12-08 | Smithkline Beecham Plc | Novel process |
| GB9923446D0 (en) * | 1999-10-04 | 1999-12-08 | Smithkline Beecham Plc | Novel process |
| US6660298B1 (en) * | 2000-07-27 | 2003-12-09 | Pentech Pharmaceuticals, Inc. | Paroxetine tablets and capsules |
| JP2004507504A (ja) * | 2000-08-28 | 2004-03-11 | シントン・ベスローテン・フェンノートシャップ | パロキセチン組成物およびその製造方法 |
| EP1791531A1 (en) * | 2004-08-20 | 2007-06-06 | Alpharma, Inc. | Paroxetine formulations |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2297550B (en) * | 1995-02-06 | 1997-04-09 | Smithkline Beecham Plc | Paroxetine hydrochloride anhydrate substantially free of bound organic solvent |
| CA2206592A1 (en) * | 1996-05-30 | 1997-11-30 | Shu-Zhong Wang | Method of producing amorphous paroxetine hydrochloride |
-
1998
- 1998-01-12 KR KR1019997006377A patent/KR20000070151A/ko not_active Application Discontinuation
- 1998-01-12 AP APAP/P/1999/001604A patent/AP9901604A0/en unknown
- 1998-01-12 NZ NZ336587A patent/NZ336587A/xx unknown
- 1998-01-12 ID IDW990687A patent/ID23250A/id unknown
- 1998-01-12 HU HU0000960A patent/HUP0000960A3/hu unknown
- 1998-01-12 JP JP53392198A patent/JP2001508460A/ja active Pending
- 1998-01-12 EA EA199900655A patent/EA002034B1/ru not_active IP Right Cessation
- 1998-01-12 EP EP98900575A patent/EP0952831A1/en not_active Withdrawn
- 1998-01-12 PL PL98334568A patent/PL334568A1/xx unknown
- 1998-01-12 WO PCT/GB1998/000081 patent/WO1998031365A1/en not_active Application Discontinuation
- 1998-01-12 CA CA002277480A patent/CA2277480A1/en not_active Abandoned
- 1998-01-12 AU AU55673/98A patent/AU730532B2/en not_active Ceased
- 1998-01-12 CN CN98803170A patent/CN1249686A/zh active Pending
- 1998-01-12 BR BR9806754-0A patent/BR9806754A/pt not_active IP Right Cessation
- 1998-01-12 TR TR1999/01622T patent/TR199901622T2/xx unknown
- 1998-01-12 IL IL13085698A patent/IL130856A/en not_active IP Right Cessation
- 1998-01-12 SK SK950-99A patent/SK95099A3/sk unknown
-
1999
- 1999-07-14 NO NO993460A patent/NO993460L/no not_active Application Discontinuation
- 1999-07-15 OA OA9900158A patent/OA11077A/en unknown
- 1999-08-10 BG BG103648A patent/BG103648A/xx unknown
-
2001
- 2001-08-03 US US09/922,072 patent/US20010049442A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104027306A (zh) * | 2014-06-25 | 2014-09-10 | 万特制药(海南)有限公司 | 帕罗西汀口服混悬液及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL130856A (en) | 2001-09-13 |
| ID23250A (id) | 2000-03-30 |
| SK95099A3 (en) | 2000-01-18 |
| JP2001508460A (ja) | 2001-06-26 |
| HUP0000960A3 (en) | 2001-04-28 |
| NZ336587A (en) | 2001-01-26 |
| EA002034B1 (ru) | 2001-12-24 |
| US20010049442A1 (en) | 2001-12-06 |
| NO993460D0 (no) | 1999-07-14 |
| KR20000070151A (ko) | 2000-11-25 |
| BR9806754A (pt) | 2000-03-14 |
| CA2277480A1 (en) | 1998-07-23 |
| EA199900655A1 (ru) | 2000-02-28 |
| WO1998031365A1 (en) | 1998-07-23 |
| AP9901604A0 (en) | 1999-09-30 |
| TR199901622T2 (xx) | 1999-09-21 |
| BG103648A (en) | 2000-04-28 |
| OA11077A (en) | 2003-03-13 |
| NO993460L (no) | 1999-09-14 |
| AU730532B2 (en) | 2001-03-08 |
| HUP0000960A2 (hu) | 2001-02-28 |
| IL130856A0 (en) | 2001-01-28 |
| EP0952831A1 (en) | 1999-11-03 |
| AU5567398A (en) | 1998-08-07 |
| PL334568A1 (en) | 2000-03-13 |
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