KR880002531A - 폴리엔 항진균성 항생제를 캡술화한 인지질 입자의 사용하는 개선된 전신 진균 간염 치료 방법 - Google Patents
폴리엔 항진균성 항생제를 캡술화한 인지질 입자의 사용하는 개선된 전신 진균 간염 치료 방법 Download PDFInfo
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- KR880002531A KR880002531A KR870009101A KR870009101A KR880002531A KR 880002531 A KR880002531 A KR 880002531A KR 870009101 A KR870009101 A KR 870009101A KR 870009101 A KR870009101 A KR 870009101A KR 880002531 A KR880002531 A KR 880002531A
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- composition
- phospholipid
- polyene antifungal
- cholesterol
- antifungal antibiotic
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- 230000000843 anti-fungal effect Effects 0.000 title claims 9
- 229940121375 antifungal agent Drugs 0.000 title claims 9
- 150000004291 polyenes Chemical class 0.000 title claims 8
- 150000003904 phospholipids Chemical class 0.000 title claims 7
- 239000002245 particle Substances 0.000 title claims 5
- 230000009885 systemic effect Effects 0.000 title claims 2
- 239000003242 anti bacterial agent Substances 0.000 title 1
- 229940088710 antibiotic agent Drugs 0.000 title 1
- 230000002538 fungal effect Effects 0.000 title 1
- 208000006454 hepatitis Diseases 0.000 title 1
- 231100000283 hepatitis Toxicity 0.000 title 1
- 239000000203 mixture Substances 0.000 claims 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 11
- 230000003115 biocidal effect Effects 0.000 claims 8
- 235000012000 cholesterol Nutrition 0.000 claims 6
- 239000008346 aqueous phase Substances 0.000 claims 5
- JCZPMGDSEAFWDY-MBMOQRBOSA-N (2s,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanamide Chemical compound NC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO JCZPMGDSEAFWDY-MBMOQRBOSA-N 0.000 claims 3
- 150000002016 disaccharides Chemical class 0.000 claims 3
- 150000002772 monosaccharides Chemical class 0.000 claims 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims 3
- 239000000243 solution Substances 0.000 claims 3
- VQJHQYFOCBRCGA-QTVWNMPRSA-N (2s,3s,4s,5s)-6-amino-2,3,4,5,6-pentahydroxyhexanal Chemical group NC(O)[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O VQJHQYFOCBRCGA-QTVWNMPRSA-N 0.000 claims 2
- 239000007983 Tris buffer Substances 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 150000002337 glycosamines Chemical class 0.000 claims 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 2
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 claims 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims 1
- 229930091371 Fructose Natural products 0.000 claims 1
- 239000005715 Fructose Substances 0.000 claims 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 1
- 206010017533 Fungal infection Diseases 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 208000031888 Mycoses Diseases 0.000 claims 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims 1
- 229960003942 amphotericin b Drugs 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 claims 1
- 229930182830 galactose Natural products 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 239000007972 injectable composition Substances 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 229960000988 nystatin Drugs 0.000 claims 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 claims 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 1
- 239000002356 single layer Substances 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
Classifications
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Nanotechnology (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (24)
- 적어도 하나의 인지질 및 콜레스테롤로 되고, 저이온 강도 수용액 상중에 현탁시킨 2000미만의 인지질 입자 중에 캡슐화된 폴리엔 항진균성 항생제로 되는 주입가능한 조성물.
- 제 1 항에 있어서, 폴릴엔 항진균성 항생제가 암포테리신 B 및 니스타틴으로 되는 군 중에서 선택되는 조성물.
- 제 1 항에 있어서, 상기 입자가 작고, 단층판의 소포인 조성물.
- 제 1 항에 있어서, 상기 입자가 입자 표면에 중량된 아민을 갖는 조성물.
- 제 4 항에 있어서, 중량된 아민이 아미노당인 조성물.
- 제 5 항에 있어서, 아미노당이 콜레스테롤의 6-아미노만노오스 유도체인 조성물.
- 제 6 항에 있어서, 조성물이 약0% 내지 약20%가 6-아미노만노오스 유도체인 조성물.
- 제 1 항에 있어서, 폴리엔 항진균성 항생제, 적어도 하나의 인지질, 콜레스테롤 및 아미노만노오스가 5-15물%의 폴리엔 항진균성 항생제, 40-90몰%의 인지질, 0.10-40몰%의 콜레스테롤 및 0-20몰%의 아미노만노오스의 몰%비로 존재하는 조성물.
- 제 1 항에 있어서, 폴리엔 항진균성 항생제의 몰%가 약 5% 내지 약 15%인 조성물.
- 제 8 항에 있어서, 폴리엔 항진균성 항생제, 적어도 하나의 인지질, 콜레스테롤 및 아미노만노오스의 몰비가 0.2:2:1인 조성물.
- 제 1 항에 있어서, 인지질이 포스파티딜글리세롤, 포스파디닐콜린, 포스파티닐세린, 포스파티딜에탄올아민 및 포스파티드 산으로 되는 군 중에서 선택되는 조성물.
- 제 11 항에 있어서, 포스파티딜콜린이 계란 포스파티딜콜린, 콩 포스파티딜콜린, 디미리스토일포스파티틸콜린, 디팔미토일포스파티딜콜린 및 디스테아로일포스파티딜콜린의 조성물.
- 제 1 항에 있어서, 콜레스테롤이 약 0.1% 내지 약 40%의 몰%로 존재하는 조성물.
- 제 1 항에 있어서, 저이온강도의 수용액상이 20밀리몰 미만의 조성물.
- 제 1 항에 있어서, 수용액 상의 pH가 약 pH 6.0 내지 약8.0인 조성물.
- 제 1 항에 있어서, 수용액상이 당용액인 조성물.
- 제16항에 있어서, 당용액이 트리스 완충액으로 완충된 단당류로 되는 조성물.
- 제17항에 있어서, 단당류가 글루코오스, 과당 및 갈락 토오스로 되는 군 중에서 선택되는 조성물.
- 제 1 항에 있어서, 수용액상이 약 4.0 내지 약6.0 중량%의 단당류로 되는 조성물.
- 제16항에 있어서, 당 용액이 트리스 완충액으로 완충된 이당류로 되는 조성물.
- 제20항에 있어서, 이당류가 수쿠로오스 및 락토오스로 되는 군 중에서 선택되는 조성물.
- 제 1 항에 있어서, 수용액상이 약 8.0 내지 약 10.0중량%이 이당류로 되는 조성물.
- 제 1 항에 있어서, 폴리엔 항진균성 항생제의 농도가 적어도 0.5mg/ml 폴리엔 항진균성 항생제인 조성물.
- 제 1 항, 제 4 항, 제 8 항, 제 11 항, 제 15 항 또는 제16항의 조성물을 정맥내 투여하는 것으로 되는 전신 진균 감염 치료 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89906486A | 1986-08-21 | 1986-08-21 | |
US899.064 | 1986-08-21 | ||
US06/899,064 | 1986-08-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR880002531A true KR880002531A (ko) | 1988-05-09 |
KR950013747B1 KR950013747B1 (ko) | 1995-11-15 |
Family
ID=25410437
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019870009101A KR950013747B1 (ko) | 1986-08-21 | 1987-08-20 | 폴리엔 항진균성 항생제를 캡술화한 인지질 입자의 제조 방법 및 이 인지질 입자로 이루어진 제약 조성물 |
Country Status (14)
Country | Link |
---|---|
US (1) | US5874104A (ko) |
EP (1) | EP0260811B1 (ko) |
JP (1) | JPH0615475B2 (ko) |
KR (1) | KR950013747B1 (ko) |
AT (1) | ATE66597T1 (ko) |
AU (1) | AU606880B2 (ko) |
CA (1) | CA1292184C (ko) |
DE (1) | DE3772498D1 (ko) |
DK (1) | DK168982B1 (ko) |
ES (1) | ES2051740T3 (ko) |
GR (1) | GR3002852T3 (ko) |
HK (1) | HK115393A (ko) |
IE (1) | IE60901B1 (ko) |
NO (1) | NO174833C (ko) |
Families Citing this family (60)
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CA1338736C (fr) * | 1986-12-05 | 1996-11-26 | Roger Baurain | Microcristaux comportant une substance active presentant une affinite pour les phospholipides, et au moins un phospholipide, procede de preparation |
FR2620028B2 (fr) * | 1986-12-05 | 1994-02-25 | Ire Celltarg Sa | Procede de preparation de microcristaux comportant a titre de substance active, notamment de l'amphotericine b, microcristaux obtenus et composition pharmaceutique en comprenant |
US4812312A (en) * | 1987-03-03 | 1989-03-14 | Board Of Regents Of The University Of Texas System | Liposome-incorporated nystatin |
US5616334A (en) * | 1987-03-05 | 1997-04-01 | The Liposome Company, Inc. | Low toxicity drug-lipid systems |
CA1338702C (en) * | 1987-03-05 | 1996-11-12 | Lawrence D. Mayer | High drug:lipid formulations of liposomal- antineoplastic agents |
US6406713B1 (en) | 1987-03-05 | 2002-06-18 | The Liposome Company, Inc. | Methods of preparing low-toxicity drug-lipid complexes |
US4999199A (en) * | 1988-11-10 | 1991-03-12 | Board Of Regents, The University Of Texas System | Pharmaceutical formulations: liposomes incorporating aromatic polyene antibiotics |
JP2653245B2 (ja) * | 1989-11-27 | 1997-09-17 | 日本新薬株式会社 | 脂肪乳剤 |
EP0567559A1 (en) * | 1991-01-14 | 1993-11-03 | The United States Of America | Anti-hiv activity of liposomal nystatin and amphotericin b |
CA2120917A1 (en) * | 1991-10-25 | 1993-04-29 | Kazumi Ogata | External preparation for treating hemorrhoidal diseases |
JP2915296B2 (ja) * | 1993-08-30 | 1999-07-05 | 宇野 潤 | 抗真菌製剤 |
GB9519654D0 (en) * | 1995-09-27 | 1995-11-29 | Nycomed Imaging As | Stabilised phospholipid compositions |
DE59710863D1 (de) * | 1996-01-25 | 2003-11-20 | Schering Ag | Verbesserte kontrastmittenlösungen für die intravasale anwendung |
GB9721901D0 (en) * | 1997-10-16 | 1997-12-17 | Univ Manchester | Particles |
WO1999027940A1 (en) * | 1997-12-01 | 1999-06-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Formulations for topical treatment of skin infections |
IT1301807B1 (it) * | 1998-06-25 | 2000-07-07 | Tiberio Bruzzese | Formulazioni farmaceutiche iniettabili di derivati della partricina. |
US6613352B2 (en) | 1999-04-13 | 2003-09-02 | Universite De Montreal | Low-rigidity liposomal formulation |
US6413537B1 (en) | 2000-03-10 | 2002-07-02 | Wisconsin Alumni Research Foundation | Nystatin formulation having reduced toxicity |
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US7651689B2 (en) * | 2002-11-15 | 2010-01-26 | Albert Einstein College Of Medicine Of Yeshiva University | Methods of applying ionization radiation for therapy of infections |
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US7846445B2 (en) * | 2005-09-27 | 2010-12-07 | Amunix Operating, Inc. | Methods for production of unstructured recombinant polymers and uses thereof |
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-
1987
- 1987-08-11 IE IE214887A patent/IE60901B1/en not_active IP Right Cessation
- 1987-08-14 EP EP87307221A patent/EP0260811B1/en not_active Expired - Lifetime
- 1987-08-14 ES ES87307221T patent/ES2051740T3/es not_active Expired - Lifetime
- 1987-08-14 DE DE8787307221T patent/DE3772498D1/de not_active Expired - Lifetime
- 1987-08-14 AT AT87307221T patent/ATE66597T1/de not_active IP Right Cessation
- 1987-08-18 AU AU77160/87A patent/AU606880B2/en not_active Expired
- 1987-08-19 NO NO873492A patent/NO174833C/no not_active IP Right Cessation
- 1987-08-19 CA CA000544830A patent/CA1292184C/en not_active Expired - Lifetime
- 1987-08-20 KR KR1019870009101A patent/KR950013747B1/ko not_active IP Right Cessation
- 1987-08-20 DK DK434187A patent/DK168982B1/da not_active IP Right Cessation
- 1987-08-21 JP JP62208049A patent/JPH0615475B2/ja not_active Expired - Fee Related
-
1991
- 1991-10-08 GR GR91401494T patent/GR3002852T3/el unknown
-
1993
- 1993-10-28 HK HK1153/93A patent/HK115393A/xx not_active IP Right Cessation
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EP0260811A2 (en) | 1988-03-23 |
DK168982B1 (da) | 1994-07-25 |
NO174833B (no) | 1994-04-11 |
NO873492L (no) | 1988-02-22 |
ES2051740T3 (es) | 1994-07-01 |
US5874104A (en) | 1999-02-23 |
NO873492D0 (no) | 1987-08-19 |
JPS6366123A (ja) | 1988-03-24 |
GR3002852T3 (en) | 1993-01-25 |
EP0260811A3 (en) | 1988-07-20 |
KR950013747B1 (ko) | 1995-11-15 |
JPH0615475B2 (ja) | 1994-03-02 |
DK434187A (da) | 1988-02-22 |
CA1292184C (en) | 1991-11-19 |
EP0260811B1 (en) | 1991-08-28 |
IE872148L (en) | 1988-02-21 |
HK115393A (en) | 1993-11-05 |
AU7716087A (en) | 1988-02-25 |
ATE66597T1 (de) | 1991-09-15 |
DK434187D0 (da) | 1987-08-20 |
AU606880B2 (en) | 1991-02-21 |
NO174833C (no) | 1994-07-20 |
IE60901B1 (en) | 1994-08-24 |
DE3772498D1 (de) | 1991-10-02 |
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