KR100298807B1 - 파킨슨씨병및파킨슨증후군의치료를위한,리루졸을포함하는제약학적조성물 - Google Patents
파킨슨씨병및파킨슨증후군의치료를위한,리루졸을포함하는제약학적조성물 Download PDFInfo
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- KR100298807B1 KR100298807B1 KR1019950702793A KR19950702793A KR100298807B1 KR 100298807 B1 KR100298807 B1 KR 100298807B1 KR 1019950702793 A KR1019950702793 A KR 1019950702793A KR 19950702793 A KR19950702793 A KR 19950702793A KR 100298807 B1 KR100298807 B1 KR 100298807B1
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A—HUMAN NECESSITIES
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- A—HUMAN NECESSITIES
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
파킨슨씨 병 파킨슨 증후군의 치료를 위한 약제의 제조에 리루졸 또는 그의 제약학적으로 허용가능한 염의 이용.
Description
본 발명은 리루졸 (6-트리플루오로메톡시-2-아미노벤조티아졸) 또는 상기 화합물의 제약학적으로 허용가능한 염의 신규한 치료학적 이용에 관한 것이다.
리루졸은 항견련성, 불안안화성 및 수면제 의약 생성물로서 (특허 EP 50,551), 정신분열증 치료에 (EP 305,276), 수면 장애 및 우울증 치료에 (EP 305,277), 뇌혈관 장애 치료에 및 마취제로서 (EP 282,971) 유용하다.
이제 놀랍게도, 상기 화합물이 또한 파킨슨씨 병 및 파킨슨 증후군의 치료에 사용될 수 있음이 밝혀졌다.
신경독 MPTP (1-메틸-4-페닐-1,2,3,6-테트라히드로피리딘)이 파킨슨씨 병과 유사한 증후군을 유발하는 것으로 알려져 있다. 상기 증후군은 영장류에서 (R.S. Burns 일동, Proc. Nat1. Acad. Sci. 80, 4546-4550 (1983)), 사람에서 (J.W. Langston 일동, Science, 219, 279-980 (1983)) 및 쥐에서 (R.E. Heikkila 일동, Science, 224, 1451-1453 (1984)) 도파민성 흑선조체 뉴우런의 변성에 기인한다.
그리하여 리루졸의 활성을 MPTP에 의해 감소되는 피질 도파민 수준을 대조군 동물의 수준과 비교하여 측정함으로써 입증했다.
20 - 25g 중량의 쥐(C57BL/6)에 MPTP 15mg/kg을 2시간 간격을 두고 3회 복강내로 주입한다. MPTP 첫번째 주입 전 30분에, 그리고나서 MPTP 첫번째 주입후 2시간 30분에, 5시간 30분에 및 7시간 30분에, 연구 생성물 1-40 mg/kg을 생성물에따라 투여한다. 다음 3일에 걸쳐, 연구 생성물 1-40 mg/kg을 생성물에따라 1일 2회 투여한다. MPTP 주입 후 8일에 쥐를 희생한다. 선조체 및 전두 피질을 절단하고 그의 분석 시간까지 -70℃에 보관한다. 도파민 수준을 고압 액체 크로마토그래피에 의해 전기화학 검출하여 측정한다. 통계학적 분석은 ANOVA 를 사용하고 쉐페 검사(Scheffe's test) 하여 수행한다.
얻어진 결과가 하기 표에 기록되어 있다.
제약학적으로 허용가능한 염으로서, 염화수소, 황산염, 질산염 또는 인산염과 같은 무기산과의 첨가 생성염, 또는 아세테이트, 프로피오네이트, 숙시네이트, 옥살레이트, 벤조에이트, 푸마레이트, 말레이트, 메탄설포네이트, 이세티오네이트, 테오필리네아세테이트, 살리실레이트, 페놀프탈리레이트 또는 메틸렌비스(β-히드록시나프토에이트)와 같은 유기산과의 첨가생성염, 또는 상기 유도체의 치환 유도체를 구체적으로 언급할 수 있다.
약제 생성물은 적어도 리루졸을 유리 형태로 또는 제약학적으로 허용가능한 산과의 첨가 생성염 형태로, 순수한 상태로 또는 불활성이거나 또는 생리학적으로 활성일 수 있는, 임의의 다른 제약학적으로 상용가능한 생성물과 혼합된 조성물 형태로 포함한다. 본 발명에 따른 약제 생성물은 경구로 또는 비경구로 사용할 수 있다.
경구 투여를 위한 고체 조성물로서, 정제, 환제, 분말 (젤라틴 캡슐, 와퍼갭슐) 또는 과립을 사용할 수 있다. 상기 조성물에서, 본 발명에 따른 활성 성분은 전분, 셀루로스, 수크로스, 락토스 또는 실리카와 같은 하나 이상의 불활성 희석제와 아르곤 스트림하에 혼합된다. 상기 조성물은 또한 희석제 이외의 물질, 예를들면, 마그네슘 스테아레이트 또는 탈크와 같은 하나 이상의 윤활제, 색소, 코우팅 (당의정) 또는 유약을 포함할 수 있다.
경구 투여를 위한 액체 조성물로서, 물, 에탄올, 글리세롤, 식물성유 또는 액체 파라핀과 같은 불활성 희석제를 함유한, 제약학적으로 허용가능한 용액, 현탁액, 유탁액, 시럽 및 엘릭시르를 사용할 수 있다. 상기 조성물은 희석제 이외의 물질, 예를들면 습윤제, 감미제, 농화제, 향미제 또는 안정화제 생성물을 포함할 수 있다.
비경구 투여를 위한 무균 조성물은 바람직하게 수성 또는 비-수성 용액, 현탁액 또는 유탁액일 수 있다. 용매 또는 부형제로서, 물, 프로필렌 글리콜, 폴리에틸렌 글리콜, 식물성유, 특히 올리브유, 주입가능 유기 에스테르, 예를들면 에틸 올레이트, 또는 다른 적합한 유기 용매를 사용할 수 있다. 상기 조성물은 또한 보조제 특히 습윤제, 강장제, 유화제, 분산제 및 안정화제를 함유할 수 있다. 멸균은 몇몇 방법, 예를들면 무균 여과에 의해, 조성물내 안정화제 혼입에 의해, 방사선 조사에 의해 또는 가열에 의해 수행할 수 있다. 상기는 또한 사용시에 무균수 또는 임의의 다른 무균 주입가능 매질에 용해될 수 있는 무균 고체 조성물의 형태로 제조될 수 있다.
사용량은 추구하는 효과, 치료 기간 및 사용되는 투여 경로에 좌우되며; 일반적으로 성인의 경우 경구 경로를 통해 50 - 400 mg/일 이고, 1회 사용량은 25 - 200 mg 의 활성 물질의 범위이다.
일반적으로 말해, 의사가 연령, 체중 및 치료하려는 주체에 특이한 모든 다른 인자들에 따라 적당한 사용량을 결정할 것이다.
하기 실시예는 본 발명에 따른 약제 생성물을 예시한다.
활성 생성물 50 mg 사용량을 함유하고 하기 조성을 갖는 정제를 통상 기술에 따라 제조한다:
- 리루졸 50 mg
- 만니톨 64 mg
- 미세결정 셀룰로스 50 mg
- 포비돈 보형제 12 mg
- 나트륨 카르복시메틸 전분 16 mg
- 탈크 4 mg
- 마그네슘 스테아레이트 2 mg
- 무수 교질 실리카 2 mg
- 메틸히드록시프로필 셀룰로스, 폴리에틸렌 글리콜 6000 및 이산화 티타늄 (72 : 3.5 : 24.5)
중량 245 mg 의 완성된 필름 코우팅 정제 1 알을 위한 충분량.
[실시예 B]
활성 생성물 50 mg 사용량을 함유하고 하기 조성을 갖는 경질 젤라틴 캡슐을 통상 기술에 따라 제조한다 :
- 리루졸 50 mg
- 셀룰로스 18 mg
- 락토스 55 mg
- 교질 실리카 1 mg
- 나트륨 카르복시메틸 전분 10 mg
- 탈크 10 mg
- 마그네슘 스테아레이트 1 mg
[실시예 C]
활성 생성물 10 mg 을 함유하고 하기 조성을 갖는 주입물을 제조한다.
- 리루졸 10 mg
- 벤조산 80 mg
- 벤질 알콜 0.06㎤
- 나트륨 벤조에이트 80 mg
- 95% 에탄올 0.4 ㎤
- 수산화 나트륨 24 mg
- 프로필렌 글리콜 1.6 ㎤
- 물 충분량 4 ㎤
본 발명은 또한 파킨슨씨 병 파킨슨 증후군의 치료에 사용될 수 있는 약제 생성물을 제조하는 방법에 관한 것으로, 리루졸 또는 상기 화합물의 제약학적으로 허용가능한 염을 하나 이상의 상용가능하고 제약학적으로 허용가능한 희석제 및/또는 보조제와 혼합하는 것으로 구성된다.
본 발명은 또한 파킨슨씨 병 또는 파킨슨 증후군을 앓는 포유류, 및 구체적으로 사람을 치료하는 방법에 관한 것으로, 리루졸 또는 상기 화합물의 제약학적으로 허용가능한 염을 유효량 투여하는 것으로 구성된다.
Claims (3)
- 리루졸 또는 이의 제약학적으로 허용가능한 염, 및 하나 이상의 상용가능하고 제약학적으로 허용가능한 희석제 또는 보조제를 포함하는, 파킨슨씨병 빛 파킨슨 증후군의 치료를 위한 제약학적 조성물.
- 제1항에 있어서, 25-200 mg의 리루졸을 포함하는 제약학적 조성물.
- 파킨슨씨 병 밀 파킨슨 증후군의 치료를 위해 사용될 수 있는 제약학적 조성물을 제조하는 방법으로서, 리루졸 또는 이의 제약학적으로 허용가능한 염을 하나 이상의 상용가능하고 제약학적으로 허용가능한 희석제 또는 보조제와 혼합하는 것을 특징으로 하는 제약학적 조성물의 제조 방법.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR93/00074 | 1993-01-07 | ||
| FR9300074A FR2700117B1 (fr) | 1993-01-07 | 1993-01-07 | Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens. |
| PCT/FR1994/000003 WO1994015601A1 (fr) | 1993-01-07 | 1994-01-03 | Application du riluzole dans le traitement de la maladie de parkinson et des syndromes parkinsoniens |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR960700054A KR960700054A (ko) | 1996-01-19 |
| KR100298807B1 true KR100298807B1 (ko) | 2001-11-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019950702793A KR100298807B1 (ko) | 1993-01-07 | 1994-01-03 | 파킨슨씨병및파킨슨증후군의치료를위한,리루졸을포함하는제약학적조성물 |
| KR1019950702794A KR960700059A (ko) | 1993-01-07 | 1995-07-06 | 파킨슨씨 병 및 파킨슨 중후군의 치료에 카르바마제핀 및 옥스카르바제핀의 이용(application of carbamazepine and oxcarbazepine in the treatment of parkinson's disease and parkinsonian syndromes) |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019950702794A KR960700059A (ko) | 1993-01-07 | 1995-07-06 | 파킨슨씨 병 및 파킨슨 중후군의 치료에 카르바마제핀 및 옥스카르바제핀의 이용(application of carbamazepine and oxcarbazepine in the treatment of parkinson's disease and parkinsonian syndromes) |
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| EP (2) | EP0678026B1 (ko) |
| JP (2) | JPH08505379A (ko) |
| KR (2) | KR100298807B1 (ko) |
| AT (2) | ATE144420T1 (ko) |
| AU (3) | AU684059B2 (ko) |
| CA (2) | CA2153340C (ko) |
| CZ (2) | CZ284363B6 (ko) |
| DE (2) | DE69400799T2 (ko) |
| DK (2) | DK0678026T3 (ko) |
| ES (2) | ES2092890T3 (ko) |
| FR (1) | FR2700117B1 (ko) |
| GR (2) | GR3020975T3 (ko) |
| HU (2) | HUT72074A (ko) |
| IL (3) | IL108285A0 (ko) |
| MX (2) | MX9307885A (ko) |
| NO (2) | NO952310L (ko) |
| PL (2) | PL309596A1 (ko) |
| RU (1) | RU2221563C2 (ko) |
| SK (2) | SK279758B6 (ko) |
| UA (1) | UA29464C2 (ko) |
| WO (3) | WO1994015610A1 (ko) |
| ZA (3) | ZA9432B (ko) |
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| US6119094A (en) * | 1996-02-29 | 2000-09-12 | Electronic Data Systems Corporation | Automated system for identifying alternate low-cost travel arrangements |
| EP1043996A2 (en) * | 1998-01-09 | 2000-10-18 | Mor-Research Applications Ltd. | Treatment of dyskinesias |
| US6417210B1 (en) | 1998-01-09 | 2002-07-09 | Mor-Research Applications Ltd. | Treatment of dyskinesias and Parkinson's disease with riluzole and levodopa |
| FR2774592B1 (fr) * | 1998-02-06 | 2000-03-17 | Rhone Poulenc Rorer Sa | Application du 2-amino-6-trifluoromethoxybenzothiazole pour la prevention ou le traitement des dysfonctionnements du cervelet |
| FR2777781B1 (fr) | 1998-04-24 | 2004-04-09 | Rhone Poulenc Rorer Sa | Associations riluzole et l-dopa pour le traitement de la maladie de parkinson |
| FR2787028B1 (fr) | 1998-12-15 | 2002-10-18 | Aventis Pharma Sa | Utilisation du riluzole dans le traitement des traumatismes acoustiques |
| US6506378B1 (en) | 1998-12-16 | 2003-01-14 | Arch Development Corporation | Vesicular monoamine transporter gene therapy in Parkinson's disease |
| FR2801793B1 (fr) * | 1999-12-01 | 2003-07-04 | Aventis Pharma Sa | Association d'une ergoline et de riluzole et son utilisation comme medicament |
| WO2002064557A2 (en) * | 2001-02-12 | 2002-08-22 | Teva Pharmaceutical Industries Ltd. | New crystal forms of oxcarbazepine and processes for their preparation |
| WO2005000294A1 (en) * | 2003-06-06 | 2005-01-06 | Pharmacia Corporation | Selective inhibitor and an anticonvulsant agent for the treatment of central nervous system disorders |
| WO2005037276A1 (en) * | 2003-10-09 | 2005-04-28 | Aventis Pharma S.A. | Use of riluzole for the treatment of essential tremor |
| CA2471666C (en) * | 2004-06-18 | 2009-10-13 | Apotex Pharmachem Inc. | An improved process for the preparation of oxcarbazepine and related intermediates |
| US9629817B2 (en) | 2005-08-25 | 2017-04-25 | Steven Michael Weiss | Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption in coronary blood flow |
| US20070248684A1 (en) * | 2006-01-31 | 2007-10-25 | Sigal Blau | Pharmaceutical formulations of oxcarbazepine and methods for its preparation |
| CA2630240A1 (en) * | 2006-01-31 | 2007-08-09 | Teva Pharmaceutical Industries Ltd. | Oxcarbazepine pharmaceutical formulation and its method of preparation, wherein oxcarbazepine has a broad and multi-modal particle size distribution |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| DE602007012236D1 (de) * | 2006-04-26 | 2011-03-10 | Supernus Pharmaceuticals Inc | Oxcarbazepin-zubereitungen für kontrollierte freisetzung mit sigmoidalem freisetzungsprofil |
| MX2010002716A (es) * | 2007-09-14 | 2010-07-05 | Scil Technology Gmbh | Uso de slit, nefrina, efrina o semaforina para el tratamiento de enfermedades de cartilago. |
| EP2389187B1 (en) | 2009-01-20 | 2016-11-16 | Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center | Sorbic and benzoic acid and derivatives thereof enhance the activity of a neuropharmaceutical |
| WO2011017319A1 (en) * | 2009-08-03 | 2011-02-10 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods of treating disorders associated with protein polymerization |
| US9072772B2 (en) | 2009-11-05 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | Methods of treating disorders associated with protein aggregation |
| US8809617B2 (en) | 2009-11-05 | 2014-08-19 | The University of Pittsburgh—Of the Commonwealth System of Higher Education | Automated high-content live animal drug screening using C. elegans |
| US9463186B2 (en) | 2013-04-15 | 2016-10-11 | Northwestern University | Treatment for dopaminergic disorders |
| CA3027297A1 (en) | 2016-06-13 | 2017-12-21 | Syneurx International (Taiwan) Corp. | Co-crystals of sodium benzoate and uses thereof |
| RU2022101542A (ru) | 2016-06-13 | 2022-02-03 | Сайньюрекс Интернэшнл (Тайвань) Корп. | Сокристаллы бензоата лития и их применения |
| US10336679B2 (en) | 2016-10-24 | 2019-07-02 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
| US11369579B2 (en) | 2016-10-24 | 2022-06-28 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
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| US10098861B1 (en) | 2017-10-24 | 2018-10-16 | Syneurx International (Taiwan) Corp. | Pharmaceutical composition comprising sodium benzoate compound and clozapine, and uses thereof |
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|---|---|---|---|---|
| US2948718A (en) * | 1960-08-09 | New n-heterocyclic compounds | ||
| CH500196A (de) * | 1969-03-10 | 1970-12-15 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Azepinderivaten |
| FR2492258A1 (fr) * | 1980-10-17 | 1982-04-23 | Pharmindustrie | Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole |
| US4431641A (en) * | 1980-10-17 | 1984-02-14 | Ciba-Geigy Corporation | Pharmaceutical compositions having antiepileptic and antineuralgic action |
| GB8613183D0 (en) * | 1986-05-30 | 1986-07-02 | Wellcome Found | Triazine salt |
| DE4118740A1 (de) * | 1991-06-05 | 1992-12-10 | Schering Ag | Neue kombinationspraeparate zur behandlung des morbus parkinson |
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-
1993
- 1993-01-07 FR FR9300074A patent/FR2700117B1/fr not_active Expired - Lifetime
- 1993-12-13 MX MX9307885A patent/MX9307885A/es not_active IP Right Cessation
-
1994
- 1994-01-03 WO PCT/FR1994/000004 patent/WO1994015610A1/fr active IP Right Grant
- 1994-01-03 CA CA002153340A patent/CA2153340C/fr not_active Expired - Lifetime
- 1994-01-03 US US08/446,734 patent/US5674885A/en not_active Expired - Lifetime
- 1994-01-03 HU HU9502065A patent/HUT72074A/hu unknown
- 1994-01-03 DE DE69400799T patent/DE69400799T2/de not_active Expired - Lifetime
- 1994-01-03 EP EP94903936A patent/EP0678026B1/fr not_active Expired - Lifetime
- 1994-01-03 WO PCT/FR1994/000003 patent/WO1994015601A1/fr active IP Right Grant
- 1994-01-03 WO PCT/FR1994/000005 patent/WO1994015607A1/fr active Application Filing
- 1994-01-03 UA UA95073383A patent/UA29464C2/uk unknown
- 1994-01-03 US US08/446,735 patent/US5658900A/en not_active Expired - Fee Related
- 1994-01-03 CZ CZ951765A patent/CZ284363B6/cs unknown
- 1994-01-03 JP JP6515743A patent/JPH08505379A/ja active Pending
- 1994-01-03 ES ES94903935T patent/ES2092890T3/es not_active Expired - Lifetime
- 1994-01-03 AU AU58188/94A patent/AU684059B2/en not_active Expired
- 1994-01-03 DK DK94903936.6T patent/DK0678026T3/da active
- 1994-01-03 RU RU2000127693/15A patent/RU2221563C2/ru active
- 1994-01-03 CZ CZ951764A patent/CZ284928B6/cs not_active IP Right Cessation
- 1994-01-03 JP JP06515742A patent/JP3120153B2/ja not_active Expired - Fee Related
- 1994-01-03 ES ES94903936T patent/ES2091689T3/es not_active Expired - Lifetime
- 1994-01-03 DK DK94903935.8T patent/DK0678023T3/da active
- 1994-01-03 EP EP94903935A patent/EP0678023B1/fr not_active Expired - Lifetime
- 1994-01-03 PL PL94309596A patent/PL309596A1/xx unknown
- 1994-01-03 PL PL94309594A patent/PL309594A1/xx unknown
- 1994-01-03 DE DE69400435T patent/DE69400435T2/de not_active Expired - Fee Related
- 1994-01-03 AU AU58190/94A patent/AU5819094A/en not_active Abandoned
- 1994-01-03 CA CA002153341A patent/CA2153341A1/fr not_active Abandoned
- 1994-01-03 KR KR1019950702793A patent/KR100298807B1/ko not_active IP Right Cessation
- 1994-01-03 HU HU9502063A patent/HU217136B/hu unknown
- 1994-01-03 AT AT94903935T patent/ATE144420T1/de active
- 1994-01-03 SK SK867-95A patent/SK279758B6/sk not_active IP Right Cessation
- 1994-01-03 AT AT94903936T patent/ATE141792T1/de not_active IP Right Cessation
- 1994-01-03 SK SK866-95A patent/SK279645B6/sk unknown
- 1994-01-03 AU AU58189/94A patent/AU677279B2/en not_active Ceased
- 1994-01-04 ZA ZA9432A patent/ZA9432B/xx unknown
- 1994-01-04 ZA ZA9426A patent/ZA9426B/xx unknown
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- 1994-01-05 MX MX9400287A patent/MX9400287A/es unknown
- 1994-01-06 IL IL10828594A patent/IL108285A0/xx unknown
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1995
- 1995-06-12 NO NO952310A patent/NO952310L/no unknown
- 1995-06-12 NO NO952309A patent/NO307495B1/no not_active IP Right Cessation
- 1995-07-06 KR KR1019950702794A patent/KR960700059A/ko not_active Application Discontinuation
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1996
- 1996-09-11 GR GR960400811T patent/GR3020975T3/el unknown
- 1996-10-24 GR GR960401906T patent/GR3021438T3/el unknown
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