HRP950405A2 - USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) AND ITS PHYSIOLOGICALLY COMPATIBLE SALTS FOR TREATING REPERFUSION DAMAGE TRIGGERED BY TEMPORARY FOCAL ISCHAEMIA - Google Patents
USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) AND ITS PHYSIOLOGICALLY COMPATIBLE SALTS FOR TREATING REPERFUSION DAMAGE TRIGGERED BY TEMPORARY FOCAL ISCHAEMIA Download PDFInfo
- Publication number
- HRP950405A2 HRP950405A2 HRP4425280.3A HRP950405A HRP950405A2 HR P950405 A2 HRP950405 A2 HR P950405A2 HR P950405 A HRP950405 A HR P950405A HR P950405 A2 HRP950405 A2 HR P950405A2
- Authority
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- Croatia
- Prior art keywords
- same
- adenosyl
- methionine
- reperfusion damage
- physiologically compatible
- Prior art date
Links
- 206010063837 Reperfusion injury Diseases 0.000 title claims description 11
- 208000028867 ischemia Diseases 0.000 title claims description 11
- 150000003839 salts Chemical class 0.000 title claims description 7
- 230000001960 triggered effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims description 4
- 229960004452 methionine Drugs 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000001052 transient effect Effects 0.000 claims 1
- 206010008118 cerebral infarction Diseases 0.000 description 6
- 230000010410 reperfusion Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000002253 anti-ischaemic effect Effects 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 201000008247 brain infarction Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- FUDAIDRKVVTJFF-UHFFFAOYSA-N butane-1,1-disulfonic acid Chemical compound CCCC(S(O)(=O)=O)S(O)(=O)=O FUDAIDRKVVTJFF-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Opis
(S)-adenosil-L-metionin (SAMe) i njegove soli su već poznate, usporedi EP-PS 162.323. Također je opisano da SAMe ima načelno antiishemijsko djelovanje (Eur. J. Pharmacol. 144: 211, 1987; Jpn. J. Pharmacol. 46: 225, 1988; Eur. J. Pharmacol. 166: 231, 1989; Jpn. J. Pharmacol. 52: 141, 1990). Prema JP-PS 8.312.642 SAMe se može upotrijebiti kod različitih indikacija koje se odnose na središnja oštećenja.
Antiishemijsko djelovanje SAMe bilo je međutim pokazano samo kod liječenja globalne cerebralne ishemije. Globalna cerebralna ishemija nastaje zbog potpunog isključenja cerebralnog snabdijevanja krvlju, kao što se pojavljuje primjerice tijekom zaustavljanja rada srca. Poznato je da se terapeutsko djelovanje tvari kod globalne ishemije ne može prenijeti na ishemijska oboljenja mozga druge vrste, osobito ne na fokalnu ishemiju koju uzrokuje začepljenje intrakranijalnih posuda (Cerebrovasc. Brain Metab. Rev. 2: 1, 1990).
Poznato je, nadalje, da kod privremene fokalne ishemije ponovno stvaranje snabdijevanja krvi uzrokuje sekundarne biokemijske procese, koji dovode do takozvanih reperfuzijskih oštećenja (Arch. Neurol. 47: 1245, 1990). Pretpostavlja se da reperfuzijska oštećenja, u prvom redu, uzrokuju slobodni kisikovi radikali (superoksid i hidroksilni radikal) (Neurosurgery 27: 1, 1990). lako je reperfuzija važna za sprječavanje ireverzibilnih oštećenja, ona sa svoje strane potiče reperfuzijska oštećenja. Zbog toga se veličina oštećenja tkiva može dalje reducirati lijekovima ako oni minimiziraju ili sprječavaju reper-fuzijska oštećenja. Ti procesi utvrđeni su kako na mozgu tako također i na srcu (Annu. Rev. Physiol. 52: 487, 1990).
Najvažniji pojavni oblici privremene fokalne ishemije, kod koje se mogu pojaviti sekundarna oštećenja ove vrste, su slijedeći: (1) akutna tromboembolijska ishemlia, gdje se reperfuzija uvodi davanjem trombolitičkih aktivnih tvari (kao urokinaza, streptokinaza ili t-PA) ili operativnim mjerama, (2) vazospazme, koje se aktiviraju spontano ili nakon davanja vazodilatorijski učinkovitih tvari, (3) kirurški zahvati, kod kojih se privremeno zatvaranje arterije vrši iz operacijsko-tehničkih razloga i (4) kratkotrajni ishemijski napadi neobjašnjive etiologije. Za sada ne postoji ni jedna priznata terapija za liječenje reperfuzijskih oštećenja, koja se pojavljuju kao popratna pojava privremene fokalne ishemije.
Predmet predloženog izuma je upotreba SAMe i njegovih fiziološki podnošljivih soli za liječenje reperfuzijskih oštećenja koja su izazvana povremenom fokalnom ishemijom. SAMe se upotrebljava u obliku soli s nekom fiziološki podnošljivom kiselinom. Kiseline jesu ponajprije: solna kiselina, sumporna kiselina, fosforna kiselina, mravlja kiselina octena kiselina, limunska kiselina, vinska kiselina, metansulfonska kiselina, p-toluensulfonska klselina i butandisulfonska kiselina.
SAMe, odnosno njegove soli daju se za te indikacije u količinama od 10 do 1000 mg/kg tjelesne težine. SAMe se može davati na uobičajen način parenteralno (intravenski, intraarterijski ili intramuskularno), pri čemu intravenska infuzija predstavlja oblik aplikacije kojem se daje prednost. Gore navedene količine infundiraju se pacijentima u pravilu jednom u vremenskom periodu od 1 do 24 sata.
SAMe se može primijeniti u upotrebljivim galenskim aplikacijskim oblicima, npr. kao otopina. Aplikacijski oblici sadrže aktivnu tvar normalno u količini od 1 do 50%, ponajprije 5 do 20%. Osobita prednost kod upotrebe SAMe u usporedbi s drugim terapijama sastoji se u tome da liječenje sa SAMe pokazuje također i istaknuto protektivno djelovanje, kad se injicira tek u fazi reperfuzije. Učinkovitost SAMe protiv reperfuzijskih oštećenja pokazuje slijedeći pokus na primjeru mozga:
Djelovanje SAMe na veličinu moždanog infarkta izazvanog privremenom fokalnom cerebralnom ishemijom bilo je istraženo na štakorima po modificiranoj metodl Chen-a et al. (Stroke 17: 738, 1986). U tu svrhu bili su pod halotanskom narkozom oslobodeni i okludirani 90 minuta desni A. cerebri media i oba Aa. carotis communes. Veličina moždanog infarkta bila je kvantitativno određena 24 sata kasnije obojenjem s trifeniltetrazolijkloridom.
U skupinama prema tvarima pokusne životinje bile su intravenozno liječene sa 40 mg/kg + 100 mg/kg/h SAMe. Davanje bolus slijedilo je ili na kraju 90-minutne okluzije ili 30 minuta kasnije; trajanje infuzije bilo je namješteno na 6 sati. Kao što se vidi iz tablice 1, privremena okluzija posude pri liječenju sa SAMe dovodi do signifikantno manjih cerebralnih infarkata nego kod obradbe sa placebom (0,9 %-tna otopina NaCl) .
Ovi nalazi objašnjavaju specifično djelovanje SAMe na reperfuzijske procese: lako je terapija sa SAMe bila injicirana tek u postishemijskoj fazi reperfuzije, ona je potaknula signifikantno ograničenje nastalog moždanog infarkta.
[image]
Claims (3)
1. Upotreba (S)-adenosil-L-metionma (SAMe) i njegovih fiziokoški podnošljivih soli, naznačena time, da se oni koriste za liječenje reperfuzijskih oštećenja izazvanih privremenom fokalnom ishemijom.
2. Upotreba (S) -adenosil-L-metionina (SAMe) i njegovih fiziokoški podnošljivih soli, naznačena time, da se oni koriste za proizvodnju lijekova za liječenje reperfuzijskih oštećenja izazvanih privremenom fokalnom ishemijom.
3. Metoda za liječenje pacijenata koji pate od reperfuzijskih oštećenja izazvanih privremenom fokalnom ishemijom, naznačena time, da im se daje učinkovitu količinu (S)-adenosil-L-metionina (SAMe).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4425280A DE4425280C2 (de) | 1994-07-16 | 1994-07-16 | Verwendung von (S)-Adenosyl-L-methionin und dessen physiologisch verträglichen Salzen zur Behandlung von Reperfusionsschäden, die nach temporärer fokaler Ischämie ausgelöst werden |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP950405A2 true HRP950405A2 (en) | 1997-10-31 |
Family
ID=6523426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP4425280.3A HRP950405A2 (en) | 1994-07-16 | 1995-07-14 | USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) AND ITS PHYSIOLOGICALLY COMPATIBLE SALTS FOR TREATING REPERFUSION DAMAGE TRIGGERED BY TEMPORARY FOCAL ISCHAEMIA |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5776911A (hr) |
| EP (1) | EP0771202A1 (hr) |
| JP (1) | JPH10502652A (hr) |
| KR (1) | KR970704442A (hr) |
| AU (1) | AU2927195A (hr) |
| BG (1) | BG101145A (hr) |
| CA (1) | CA2195345A1 (hr) |
| CZ (1) | CZ12297A3 (hr) |
| DE (1) | DE4425280C2 (hr) |
| FI (1) | FI970165A (hr) |
| HR (1) | HRP950405A2 (hr) |
| HU (1) | HUT76834A (hr) |
| IL (1) | IL114540A0 (hr) |
| NO (1) | NO970185L (hr) |
| PL (1) | PL318318A1 (hr) |
| SI (1) | SI9520087A (hr) |
| WO (1) | WO1996002252A1 (hr) |
| ZA (1) | ZA955865B (hr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19515275A1 (de) * | 1995-04-26 | 1996-10-31 | Knoll Ag | Neue Verwendung von (S)-Adenosyl-L-methionin(SAMe) |
| IT1317920B1 (it) * | 2000-10-20 | 2003-07-15 | Univ Roma | S-adenosilmetionina e suoi derivati per il trattamento e laprevenzione della malattia di alzheimer. |
| US8841344B2 (en) | 2002-10-03 | 2014-09-23 | Hill's Pet Nutrition, Inc. | Method of using omega-3 fatty acids |
| FR2884421B1 (fr) | 2005-04-15 | 2007-08-10 | Virbac Sa | Nouveaux moyens de regulation des troubles du comportement chez les animaux de compagnie |
| AU2006237346B2 (en) * | 2005-04-20 | 2011-04-07 | Basf Plant Science Gmbh | Expression cassettes for seed-preferential expression in plants |
| WO2009114939A1 (en) | 2008-03-17 | 2009-09-24 | National Research Council Of Canada | Aromatic prenyltransferase from hop |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1173990B (it) * | 1984-05-16 | 1987-06-24 | Bioresearch Spa | Sali stabili della solfo-adenosil-l-metionina (same) particolarmente adatti per uso parenterale |
| JPH0770235B2 (ja) * | 1988-06-24 | 1995-07-31 | 株式会社東芝 | 不揮発性メモリ回路装置 |
| JPH02290896A (ja) * | 1989-04-28 | 1990-11-30 | Fuji Kagaku Kogyo Kk | 新規なｓ―アデノシルメチオニン誘導体 |
-
1994
- 1994-07-16 DE DE4425280A patent/DE4425280C2/de not_active Expired - Fee Related
-
1995
- 1995-07-05 CZ CZ97122A patent/CZ12297A3/cs unknown
- 1995-07-05 JP JP8504640A patent/JPH10502652A/ja active Pending
- 1995-07-05 CA CA002195345A patent/CA2195345A1/en not_active Abandoned
- 1995-07-05 AU AU29271/95A patent/AU2927195A/en not_active Abandoned
- 1995-07-05 US US08/776,006 patent/US5776911A/en not_active Expired - Lifetime
- 1995-07-05 WO PCT/EP1995/002598 patent/WO1996002252A1/de not_active Application Discontinuation
- 1995-07-05 HU HU9700130A patent/HUT76834A/hu unknown
- 1995-07-05 PL PL95318318A patent/PL318318A1/xx unknown
- 1995-07-05 KR KR1019970700288A patent/KR970704442A/ko not_active Application Discontinuation
- 1995-07-05 SI SI9520087A patent/SI9520087A/sl unknown
- 1995-07-05 EP EP95924974A patent/EP0771202A1/de not_active Withdrawn
- 1995-07-11 IL IL11454095A patent/IL114540A0/xx unknown
- 1995-07-14 HR HRP4425280.3A patent/HRP950405A2/hr not_active Application Discontinuation
- 1995-07-14 ZA ZA955865A patent/ZA955865B/xx unknown
-
1997
- 1997-01-15 FI FI970165A patent/FI970165A/fi not_active Application Discontinuation
- 1997-01-15 NO NO970185A patent/NO970185L/no unknown
- 1997-01-17 BG BG101145A patent/BG101145A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI970165A (fi) | 1997-03-14 |
| SI9520087A (en) | 1997-08-31 |
| US5776911A (en) | 1998-07-07 |
| PL318318A1 (en) | 1997-06-09 |
| CZ12297A3 (cs) | 1998-04-15 |
| MX9700439A (es) | 1998-05-31 |
| NO970185D0 (no) | 1997-01-15 |
| ZA955865B (en) | 1997-01-14 |
| BG101145A (en) | 1997-08-29 |
| FI970165A0 (fi) | 1997-01-15 |
| HU9700130D0 (en) | 1997-02-28 |
| WO1996002252A1 (de) | 1996-02-01 |
| CA2195345A1 (en) | 1996-02-01 |
| DE4425280C2 (de) | 1997-05-07 |
| NO970185L (no) | 1997-03-12 |
| DE4425280A1 (de) | 1996-01-18 |
| EP0771202A1 (de) | 1997-05-07 |
| JPH10502652A (ja) | 1998-03-10 |
| HUT76834A (en) | 1997-11-28 |
| IL114540A0 (en) | 1995-11-27 |
| KR970704442A (ko) | 1997-09-06 |
| AU2927195A (en) | 1996-02-16 |
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