KR950702579A - 트롬빈 억제제(thrombin inhibitors) - Google Patents
트롬빈 억제제(thrombin inhibitors) Download PDFInfo
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- KR950702579A KR950702579A KR1019950700039A KR19950700039A KR950702579A KR 950702579 A KR950702579 A KR 950702579A KR 1019950700039 A KR1019950700039 A KR 1019950700039A KR 19950700039 A KR19950700039 A KR 19950700039A KR 950702579 A KR950702579 A KR 950702579A
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- polypeptide
- thrombin
- extract
- inhibitory activity
- leech
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- 229940122388 Thrombin inhibitor Drugs 0.000 title claims 3
- 239000003868 thrombin inhibitor Substances 0.000 title claims 3
- 241000722121 Theromyzon tessulatum Species 0.000 claims abstract description 3
- 229920001184 polypeptide Polymers 0.000 claims abstract 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 14
- 239000000284 extract Substances 0.000 claims abstract 8
- 241000545744 Hirudinea Species 0.000 claims abstract 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 4
- 208000007536 Thrombosis Diseases 0.000 claims abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 3
- 230000028327 secretion Effects 0.000 claims abstract 3
- 241000237651 Rhynchobdellida Species 0.000 claims abstract 2
- 238000004007 reversed phase HPLC Methods 0.000 claims description 3
- 238000002523 gelfiltration Methods 0.000 claims description 2
- 108090000190 Thrombin Proteins 0.000 claims 7
- 230000002401 inhibitory effect Effects 0.000 claims 7
- 229960004072 thrombin Drugs 0.000 claims 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims 2
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims 2
- 238000001042 affinity chromatography Methods 0.000 claims 2
- 239000008280 blood Substances 0.000 claims 2
- 210000004369 blood Anatomy 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 238000001727 in vivo Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- VIGKUFXFTPWYER-BIIVOSGPSA-N Ala-Cys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N VIGKUFXFTPWYER-BIIVOSGPSA-N 0.000 claims 1
- NXDXECQFKHXHAM-HJGDQZAQSA-N Arg-Glu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NXDXECQFKHXHAM-HJGDQZAQSA-N 0.000 claims 1
- GKKUBLFXKRDMFC-BQBZGAKWSA-N Asn-Pro-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O GKKUBLFXKRDMFC-BQBZGAKWSA-N 0.000 claims 1
- JPHYJQHPILOKHC-ACZMJKKPSA-N Glu-Asp-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JPHYJQHPILOKHC-ACZMJKKPSA-N 0.000 claims 1
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 claims 1
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 claims 1
- XTONYTDATVADQH-CIUDSAMLSA-N Lys-Cys-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O XTONYTDATVADQH-CIUDSAMLSA-N 0.000 claims 1
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 claims 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 claims 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 claims 1
- 206010050661 Platelet aggregation inhibition Diseases 0.000 claims 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 claims 1
- JLMZKEQFMVORMA-SRVKXCTJSA-N Pro-Pro-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 JLMZKEQFMVORMA-SRVKXCTJSA-N 0.000 claims 1
- COAHUSQNSVFYBW-FXQIFTODSA-N Ser-Asn-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O COAHUSQNSVFYBW-FXQIFTODSA-N 0.000 claims 1
- LALNXSXEYFUUDD-GUBZILKMSA-N Ser-Glu-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LALNXSXEYFUUDD-GUBZILKMSA-N 0.000 claims 1
- 241000722124 Theromyzon Species 0.000 claims 1
- 108010077245 asparaginyl-proline Proteins 0.000 claims 1
- 238000011210 chromatographic step Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 108010050848 glycylleucine Proteins 0.000 claims 1
- 108010077515 glycylproline Proteins 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims 1
- 239000004019 antithrombin Substances 0.000 abstract description 3
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/855—Proteins from animals other than mammals or birds
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 린보브델리다 목, 특히 쎄로마이존 테슐라튬 종 거머리의 조직 또는 분비물의 추출물로 부터 수득할 수 있는 항트롬빈 활성을 갖는 신규한 폴리펩티드에 관한 것이다. 상기 폴리펩티드는 약 14kD, 9kD 및 3kD의 분자량을 가지며 혈정증 관련 질환 및 관련 질환 증상의 치료를 위한 약학 조성물에 사용할 수 있다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 친화성 컬럼으로 부터의 항트롬빈의 유출 프로파일을 도시한다(실시예 3),
제2도는 바이오겔 P4에서의 쎄로마이존 테슐라튬(Theromyzon tessulatum)으로 부터 유래된 항트롬빈의 겔 여과 분석을 도시한다(실시예 4),
제3도는 친화성 단계로 부터의 양성 분획들의 분석 RP-HPLC를 도시한다(실시예 5),
제4도는 친화성 단계로 부터의 양성 분획들의 예비 RP-HPLC를 도시한다(실시예 5),
제5도는 HPLC상에서의 본 발명에 따른 억제제와 히루딘의 비교를 도시한다(실시예 6).
Claims (16)
- 수용성 성분을 포함하는 린코브델리다(Rhynchobdellida) 목 거머리의 조직 또는 분비물로 부터의 트롬비 억제 활성을 갖는 추출물.
- 제1항에 있어서, 쎄로마이존(Theromyzon)과 거머리의 추출물.
- 제2항에 있어서, 쎄로마이존 테슐라튬(Theromyzon tessulatum)종 거머리의 추출물.
- 동결 및 동결건조된 거머리의 앞부분 1/3을 물/아세톤으로 균질화시켜 수득한 추출물을 트롬빈 특이적 친화성 크로마토그래피에 이어서 하나이상의 겔 여과 단계 및 하나이상의 역상 HPLC 단계에 의해 정제시킴으로써 제1항 내지 제3항중 어느 한 항에 따른 추출물로 부터 수득할 수 있는 트롬빈 억제 활성을 갖는 필수적으로 정제된 폴리펩티드.
- 제4항에 있어서, 트롬빈 억제 활성을 갖고 분자량이 약 3kD인 하나이상의 폴리펩티드로 이루어진 폴리펩티드.
- 제4항에 있어서, 트롬빈 억제 활성, 약 9kD의 분자량 및 N-말단 아미노산 서열 : Glu Asp Asp Asn Pro Gly Pro Pro Arg Ala Cys Pro Gly Glu를 갖는 하나이상의 폴리펩티드로 이루어진 폴리펩티드.
- 제4항에 있어서, 트롬빈 억제 활성, 약 14kD의 분자량 및 N-말단 아미노산 서열 : Ser Glu Leu Gly Gln Ser Lys Glu Asn Pro Cys Pro Ser Asn Met Lys Cys Asn Arg Glu Thr Phe Lys를 갖는 하나이상의 폴리펩티드로 이루어진 폴리펩티드.
- 린코브델리다 목, 바람직하게 쎄로마이존 테슐라튬 종 거머리의 조직 또는 분비물을 균질화시키고 상기 거머리의 수용성 성분을 포함하는 분획을 제조함에 의한 제1항 내지 3항중 어느 한 항에 따른 추출물의 제조방법.
- 트롬빈 특이적 친화성 크로마토그래피 및 하나이상의 추가의 표준크로마토그래피 단계에 의해 제8항에 따른 추출물을 정제시킴에 의한 제4항 내지 제7항중 어느 한 항에 따른 폴리펩티드의 제조방법.
- 약제로서 사용하기 위한 제4항 내지 7항중 어느 한 항에 따른 폴리펩티드.
- 제10항에 있어서, 혈전증 관련 질환의 생체내 치료를 위한 트롬빈 억제제인 폴리펩티드.
- 제10항에 있어서, 생체외용 혈액의 혈소판 응집 억제를 위한 트롬빈 억제제인 폴리펩티드.
- 제4항 내지 7항 및 10항 내지 12항중 어느 한 항에 따른 폴리펩티드 및 약학적으로 허용가능한 담체를 포함하는 약학 조성물.
- 혈전증 관련 질환의 생체내 치료용 약학 조성물의 제조를 위한 제4항 내지 7항중 어느 한 항에 따른 폴리펩티드의 용도.
- 생체외용 혈액의 혈소판 응집 억제용 약학 조성물의 제조를 위한 제4항 내지 7항중 어느 한 항에 따른 폴리펩티드의 용도.
- 트롬진 억제 화합물을 제조하기 위한, 린코브델리다 목, 바람직하게 쎄로마이존 테슐라튬 종 거머리의 용도.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9309509 | 1993-05-07 | ||
| GB9309509.9 | 1993-05-07 | ||
| GB939309509A GB9309509D0 (en) | 1993-05-07 | 1993-05-07 | Thrombin inhibitors |
| PCT/EP1994/001404 WO1994026777A1 (en) | 1993-05-07 | 1994-05-03 | Thrombin inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR950702579A true KR950702579A (ko) | 1995-07-29 |
| KR100335536B1 KR100335536B1 (ko) | 2002-11-11 |
Family
ID=10735154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019950700039A Expired - Fee Related KR100335536B1 (ko) | 1993-05-07 | 1994-05-03 | 트롬빈억제제 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5583111A (ko) |
| EP (1) | EP0652900B1 (ko) |
| JP (1) | JP3537437B2 (ko) |
| KR (1) | KR100335536B1 (ko) |
| AT (1) | ATE208793T1 (ko) |
| AU (1) | AU682368B2 (ko) |
| CA (1) | CA2139652C (ko) |
| CZ (1) | CZ287794B6 (ko) |
| DE (1) | DE69429062T2 (ko) |
| DK (1) | DK0652900T3 (ko) |
| ES (1) | ES2167364T3 (ko) |
| GB (1) | GB9309509D0 (ko) |
| HU (1) | HU226243B1 (ko) |
| NO (1) | NO318017B1 (ko) |
| PL (1) | PL179215B1 (ko) |
| PT (1) | PT652900E (ko) |
| RU (1) | RU2138275C1 (ko) |
| SK (1) | SK282860B6 (ko) |
| TW (1) | TW369541B (ko) |
| UA (1) | UA43831C2 (ko) |
| WO (1) | WO1994026777A1 (ko) |
| ZA (1) | ZA943171B (ko) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003512303A (ja) * | 1999-08-06 | 2003-04-02 | ジェネンテック・インコーポレーテッド | 因子ｖｉｉａのペプチドアンタゴニスト |
| GB9930659D0 (en) * | 1999-12-24 | 2000-02-16 | Bio Discovery Ltd | Inhibitors of complement activation |
| FR2834293B1 (fr) * | 2002-01-03 | 2005-02-04 | Ricarimpex | Extraits de sangsues a effet psychosomatique |
| US7164002B2 (en) | 2002-02-06 | 2007-01-16 | Genentech, Inc. | FVIIa antagonists |
| WO2007038749A2 (en) * | 2005-09-28 | 2007-04-05 | Biovascular, Inc. | Methods and compositions for blocking platelet and cell adhesion, cell migration and inflammation |
| US20110034396A1 (en) * | 2005-09-28 | 2011-02-10 | Biovascular, Inc. | Methods and compositions for inhibiting cell migration and treatment of inflammatory conditions |
| CN101095697A (zh) * | 2006-06-28 | 2008-01-02 | 李振国 | 水蛭和/或地龙分子量5800道尔顿以下的提取物 |
| RU2366441C2 (ru) * | 2007-08-03 | 2009-09-10 | Государственное учреждение гематологический научный центр Российской академии медицинских наук (ГУ ГНЦ РАМН) | Антикоагулянтное средство на основе биологически активного комплекса из коры кедра сибирского |
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| RU2519741C2 (ru) * | 2012-06-25 | 2014-06-20 | Общество с ограниченной ответственностью Научно-внедренческая фирма "Гируд И.Н." (ООО НВФ "Гируд И.Н.") | Фармацевтическая композиция, обладающая противотромботическим, тромболитическим, иммуномодулирующим, противовоспалительным действиями, нормализующая липидный и углеводный обмен |
| US8784896B2 (en) | 2012-09-17 | 2014-07-22 | Biopep Solutions, Inc | Antioxidant therapy with a whole, leech saliva extract |
| CN108395475B (zh) * | 2018-03-29 | 2021-09-10 | 苏州至汇生物科技有限公司 | 一种基于亲和层析的水蛭素分离纯化方法 |
| CN116987181B (zh) * | 2023-09-27 | 2023-12-08 | 北京元延医药科技股份有限公司 | 高生物学活性的天然水蛭素和高收率制备它们的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3432596A (en) * | 1967-10-13 | 1969-03-11 | Dresden Arzneimittel | Method for producing highly pure hirudine |
| US4390630A (en) * | 1980-10-28 | 1983-06-28 | The Regents Of The University Of California | Hementin--a fibrinolytic agent |
| DE3689525D1 (de) * | 1985-07-17 | 1994-02-24 | Hoechst Ag | Neue Polypeptide mit blutgerinnungshemmender Wirkung, Verfahren zu deren Herstellung bzw. Gewinnung, deren Verwendung und diese enthaltende Mittel. |
| ES2052062T3 (es) * | 1988-06-11 | 1994-07-01 | Ciba Geigy Ag | Nuevos polipeptidos con actividad anticoagulante. |
| GB8826428D0 (en) * | 1988-11-11 | 1988-12-14 | Biopharm Ltd | Antithrombin |
| ES2107460T3 (es) * | 1990-04-06 | 1997-12-01 | Merck Patent Gmbh | Tratamiento de la trombosis. |
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1993
- 1993-05-07 GB GB939309509A patent/GB9309509D0/en active Pending
-
1994
- 1994-03-05 UA UA95018001A patent/UA43831C2/uk unknown
- 1994-05-03 EP EP94916187A patent/EP0652900B1/en not_active Expired - Lifetime
- 1994-05-03 CA CA002139652A patent/CA2139652C/en not_active Expired - Fee Related
- 1994-05-03 AU AU67950/94A patent/AU682368B2/en not_active Ceased
- 1994-05-03 AT AT94916187T patent/ATE208793T1/de not_active IP Right Cessation
- 1994-05-03 JP JP52489694A patent/JP3537437B2/ja not_active Expired - Fee Related
- 1994-05-03 RU RU95105983A patent/RU2138275C1/ru not_active IP Right Cessation
- 1994-05-03 KR KR1019950700039A patent/KR100335536B1/ko not_active Expired - Fee Related
- 1994-05-03 PL PL94307088A patent/PL179215B1/pl not_active IP Right Cessation
- 1994-05-03 HU HU9500038A patent/HU226243B1/hu not_active IP Right Cessation
- 1994-05-03 PT PT94916187T patent/PT652900E/pt unknown
- 1994-05-03 ES ES94916187T patent/ES2167364T3/es not_active Expired - Lifetime
- 1994-05-03 SK SK8-95A patent/SK282860B6/sk not_active IP Right Cessation
- 1994-05-03 DK DK94916187T patent/DK0652900T3/da active
- 1994-05-03 CZ CZ199542A patent/CZ287794B6/cs not_active IP Right Cessation
- 1994-05-03 WO PCT/EP1994/001404 patent/WO1994026777A1/en active IP Right Grant
- 1994-05-03 DE DE69429062T patent/DE69429062T2/de not_active Expired - Lifetime
- 1994-05-03 US US08/362,567 patent/US5583111A/en not_active Expired - Lifetime
- 1994-05-06 ZA ZA943171A patent/ZA943171B/xx unknown
- 1994-08-02 TW TW083107061A patent/TW369541B/zh not_active IP Right Cessation
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1995
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Also Published As
| Publication number | Publication date |
|---|---|
| TW369541B (en) | 1999-09-11 |
| EP0652900B1 (en) | 2001-11-14 |
| JP3537437B2 (ja) | 2004-06-14 |
| DE69429062D1 (de) | 2001-12-20 |
| GB9309509D0 (en) | 1993-06-23 |
| AU6795094A (en) | 1994-12-12 |
| UA43831C2 (uk) | 2002-01-15 |
| SK282860B6 (sk) | 2002-12-03 |
| CZ287794B6 (en) | 2001-02-14 |
| RU2138275C1 (ru) | 1999-09-27 |
| DK0652900T3 (da) | 2002-02-25 |
| EP0652900A1 (en) | 1995-05-17 |
| CZ4295A3 (en) | 1995-10-18 |
| AU682368B2 (en) | 1997-10-02 |
| CA2139652C (en) | 2003-03-18 |
| PL179215B1 (pl) | 2000-08-31 |
| KR100335536B1 (ko) | 2002-11-11 |
| NO950075L (no) | 1995-01-06 |
| CA2139652A1 (en) | 1994-11-24 |
| US5583111A (en) | 1996-12-10 |
| RU95105983A (ru) | 1997-02-27 |
| PL307088A1 (en) | 1995-05-02 |
| ATE208793T1 (de) | 2001-11-15 |
| WO1994026777A1 (en) | 1994-11-24 |
| HU226243B1 (en) | 2008-07-28 |
| ZA943171B (en) | 1995-01-11 |
| HU9500038D0 (en) | 1995-03-28 |
| NO318017B1 (no) | 2005-01-24 |
| DE69429062T2 (de) | 2002-06-20 |
| PT652900E (pt) | 2002-05-31 |
| SK895A3 (en) | 1995-05-10 |
| HUT70215A (en) | 1995-09-28 |
| JPH07508765A (ja) | 1995-09-28 |
| ES2167364T3 (es) | 2002-05-16 |
| NO950075D0 (no) | 1995-01-06 |
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