HRP960196A2 - NOVEL USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) - Google Patents
NOVEL USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) Download PDFInfo
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- HRP960196A2 HRP960196A2 HR19515275.1A HRP960196A HRP960196A2 HR P960196 A2 HRP960196 A2 HR P960196A2 HR P960196 A HRP960196 A HR P960196A HR P960196 A2 HRP960196 A2 HR P960196A2
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- adenosyl
- methionine
- ischemia
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- 208000028867 ischemia Diseases 0.000 claims description 17
- 230000006378 damage Effects 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 208000027418 Wounds and injury Diseases 0.000 claims description 7
- 208000014674 injury Diseases 0.000 claims description 7
- 229960004452 methionine Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- 230000000694 effects Effects 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
- 150000007513 acids Chemical class 0.000 description 2
- 230000002253 anti-ischaemic effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 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
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 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
- 206010001526 Air embolism Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000034656 Contusions 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
- 208000005189 Embolism Diseases 0.000 description 1
- 206010073681 Epidural haemorrhage Diseases 0.000 description 1
- 208000003241 Fat Embolism Diseases 0.000 description 1
- 206010053172 Fatal outcomes Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010054805 Macroangiopathy Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000006011 Stroke Diseases 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
- 206010047163 Vasospasm Diseases 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply 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
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 206010062198 microangiopathy Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 239000008215 water for injection Substances 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(S)-adenosil-L-metionina (SAMe) i njegove soli su već poznate, usporedi EP-PS 162.323. Također je opisano da SAMe posjeduje načelnu antiishemijsku učinkovitost (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 1.686.947 SAMe se može upotrijebiti kod različitih indikacija koje se odnose na središnja ozljede. U tom spisu navode se dnevne doze od 100 mg do 1550 mg. (S)-adenosyl-L-methionine (SAMe) and its salts are already known, compare EP-PS 162,323. SAMe has also been described to possess in principle anti-ischemic efficacy (Eur. J. Pharmacol. 144: 211, 1987; Jpn. J. Pharmacol. 46: 225, 1988; Eur. J. Pharmacol. 166: 231, 1989; Jpn. J. Pharmacol. 52: 141, 1990). According to JP-PS 1,686,947 SAMe can be used for various indications related to central injuries. In that file, daily doses from 100 mg to 1550 mg are stated.
Iz Atti e Memorie della Societa Medica del Lazio, Anno I, Nr. 3, 1983, 1-14, poznato je da se s dozama SAMe od 3, odnosno 5 g/dnevno liječe pacijenti kojima su otkazali bubrezi. From Atti e Memorie della Societa Medica del Lazio, Anno I, Nr. 3, 1983, 1-14, it is known that SAMe doses of 3 and 5 g/day are used to treat patients with kidney failure.
U Japan, J. Pharmacol. 49, 119-124 (1989) opisuje se učinak SAMe na sadržaj kalcija i metabolizam glukoze, te na smrtnost štakora nakon prevladavanja ishemije kod doziranja od 100 mg/kg. In Japan, J. Pharmacol. 49, 119-124 (1989) describes the effect of SAMe on calcium content and glucose metabolism, and on rat mortality after overcoming ischemia at a dosage of 100 mg/kg.
Međutim, antiishemijska učinkovitost SAMe bila je pokazana kod liječenja globalne i prijenosne cerebralne ishemije. Uzrok globalne cerebralne ishemije potpuni prekid cerebralnog snabdijevanja krvlju, kako se pojavljuje primjerice tijekom zaustavljanja srca. Poznato je da terapeutski učinak tvari kod globalne ishemije nije prenosiv na ishemijska oboljenja mozga druge vrste, naročito ne na folaknu ishemiju, koju izaziva npr. začepljenje intrakranijalnih krvnih žila (Cerebrovasc. Brain Metab. Rev. 2: 1, 1990). However, the anti-ischemic efficacy of SAMe has been demonstrated in the treatment of global and transient cerebral ischemia. The cause of global cerebral ischemia is a complete interruption of the cerebral blood supply, as occurs, for example, during cardiac arrest. It is known that the therapeutic effect of the substance in global ischemia is not transferable to ischemic brain diseases of another type, especially not to folate ischemia, which is caused, for example, by blockage of intracranial blood vessels (Cerebrovasc. Brain Metab. Rev. 2: 1, 1990).
Najvažnije patogeneze fokalne ishemije, kod kojih se mogu pojaviti ozljede, sve do letalnog ishoda, jesu slijedeće: The most important pathogenesis of focal ischemia, which can cause injuries, up to a fatal outcome, are the following:
- Akutna embolijska ishemija, npr. kardijalna embolija, masna i zračna embolija. - Acute embolic ischemia, eg cardiac embolism, fat and air embolism.
- Trombotička ishemija, u koju spadaju takozvane cerebralne mikro- i makroangiopatije. - Thrombotic ischemia, which includes the so-called cerebral micro- and macroangiopathies.
- Hemodinamičke, tj. npr. fokalne ishemije uzrokovane vazospazmama. - Hemodynamic, i.e. focal ischemia caused by vasospasms.
- Ishemije izazvane imunološkim, upalnim mehanizmima. Tu spadaju također i fokalne ishemije izazvane hemostaziološkim i imunološkim sistemskim oboljenjima. - Ischemia caused by immune, inflammatory mechanisms. This also includes focal ischemia caused by hemostasiological and immune system diseases.
- Fokalne ishemije, koje su povezane s posebnim oblicima procesa u krvnim žilama i drugim neobičnim uzrocima. - Focal ischemias, which are associated with special forms of processes in blood vessels and other unusual causes.
- Traumatska oštećenja mozga i kičmene moždine, koje izravno ili posredno dovode do fokalne ishemije (kao npr. intracerebralna, subduralna, epiduralna krvarenja, kontuzije mozga koji traže prostor i laceracije). - Traumatic damage to the brain and spinal cord, which directly or indirectly leads to focal ischemia (such as intracerebral, subdural, epidural hemorrhages, contusions of the brain that require space and lacerations).
Predmet predloženog izuma je upotreba SAMe i njegovih fiziološki podnošljivih soli u dozama od najmanje 2000 mg/dan/pacijentu za parenteralno liječenje ozljeda koje izaziva fokalna permanentna ishemija. The subject of the proposed invention is the use of SAMe and its physiologically tolerable salts in doses of at least 2000 mg/day/patient for parenteral treatment of injuries caused by focal permanent ischemia.
SAMe se upotrebljava ponajprije u obliku soli s fiziološki podnošljivim kiselinama. Kiseline su ponajprije: solna kiselina, sumporna kiselina, fosforna kiselina, mravlja kiselina, octena kiselina, limunska kiselina, vinska kiselina, metansulfonska kiselina, p-toluol-sulfonska kiselina i butandisulfonska kiselina. SAMe is used primarily in the form of salts with physiologically tolerable acids. The acids are preferably: hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, citric acid, tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and butanedisulfonic acid.
SAMe, odnosno njegove soli za gore navedene indikacije predviđaju se, odnosno preporučuju količinama od najmanje 2000 mg/danu/pacijentu, naročito najmanje 3000 mg/danu/pacijentu, i ponajprije u dozama od najmanje 7000 mg/danu/pacijentu. Navod visoke doze prema izumu je uglavnom mjerilo kod očigledne priprave lijeka. SAMe, i.e. its salts for the above-mentioned indications are prescribed or recommended in amounts of at least 2000 mg/day/patient, especially at least 3000 mg/day/patient, and preferably in doses of at least 7000 mg/day/patient. The indication of a high dose according to the invention is mainly a criterion in the obvious preparation of the drug.
SAMe se daje na uobičajen način parenteralno (intravenski, intraarterijski ili intramuskularno), pri čemu intravensko davanje predstavlja oblik aplikacije kojem se daje prednost. Gore navedene količine mogu se infundirati pacijentu više dana u vremenskom razmaku od 1 do 24 sata. SAMe is conventionally administered parenterally (intravenously, intra-arterially or intramuscularly), with intravenous administration being the preferred form of administration. The above amounts can be infused into the patient over several days at intervals of 1 to 24 hours.
SAMe, odnosno njegove soli mogu se primijeniti tekući u galenski upotrebljivim alikacijskim oblicima, npr. kao otopine. Aplikacijski oblici sadrže aktivnu tvar normalno količinom od 1 do 50%, ponajprije 5 do 20%. SAMe, i.e. its salts, can be applied liquid in galenically usable aliquot forms, for example as solutions. Application forms contain the active substance normally in an amount of 1 to 50%, preferably 5 to 20%.
Za upotrebu prema izumu naročiti su prikladni aplikacijski oblici koji sadrže 6-18 mas. % SAMe s lizinom u vodi. Jedan takav aplikacijski oblik može imati npr. slijedeći sastav: 400 mg SAMe, 324,3 mg L-lizina, 11,5 mg NaOH i 472,1 mg vode za injekcije. For use according to the invention, application forms containing 6-18 wt. % SAMe with lysine in water. One such application form can have, for example, the following composition: 400 mg of SAMe, 324.3 mg of L-lysine, 11.5 mg of NaOH and 472.1 mg of water for injections.
Iznenađujuće se je pokazalo, da se kod upotrebe SAMe u području doza većih od 2000 mg kod liječenja fokalne ishemije, u usporedbi prema drugim terapijama, pojavljuje učinak smanjenja smrtnosti. Surprisingly, it has been shown that when SAMe is used in the range of doses higher than 2000 mg in the treatment of focal ischemia, compared to other therapies, the effect of reducing mortality appears.
Učinak smanjenja smrtnosti SAMe kod ozljeda zbog ishemije pokazuju slijedeća klinička istraživanja na primjeru mozga: The effect of reducing the mortality of SAMe in injuries due to ischemia is shown by the following clinical studies on the example of the brain:
Na pacijentima s udarom kapi, pod uvjetima dvostruke slijepe probe, bile su provedene dvije studije kontrolirane s placebom. Pacijenti podijeljeni u dvije skupine bili su liječeni intravenski 14 dana s 2400 ili 3200 mg SAMe dnevno. Pod tim uvjetima nisu se pojavili nikakvi sporedni efekti vrijedni spomena. Kako se vidi iz tablice 1, liječenje sa SAMe dovelo je u obje skupine do signifikantno niže smrtnosti nego u skupini koja je dobivala placebo. Posebnost ove studije je, da je liječenje pacijenata u pravilu započelo između 12-24 sati nakon ishemijskog inzulta, tj. da se je više sati nakon pojave poremećaja protoka krvi još uvijek mogao dokazati klinički učinak. Two placebo-controlled studies were conducted on stroke patients under double-blind conditions. Patients divided into two groups were treated intravenously for 14 days with 2400 or 3200 mg of SAMe per day. Under these conditions, no side effects worth mentioning appeared. As can be seen from table 1, treatment with SAMe led to significantly lower mortality in both groups than in the placebo group. The peculiarity of this study is that, as a rule, the treatment of patients started between 12-24 hours after the ischemic insult, i.e. that many hours after the onset of blood flow disorders, a clinical effect could still be demonstrated.
Tablica 1 Table 1
[image] [image]
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19515275A DE19515275A1 (en) | 1995-04-26 | 1995-04-26 | New use of (S) -denosyl-L-methionine (SAMe) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960196A2 true HRP960196A2 (en) | 1998-02-28 |
Family
ID=7760373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR19515275.1A HRP960196A2 (en) | 1995-04-26 | 1996-04-24 | NOVEL USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0822820A1 (en) |
| JP (1) | JPH11504023A (en) |
| KR (1) | KR19990008061A (en) |
| CN (1) | CN1182367A (en) |
| AR (1) | AR001687A1 (en) |
| AU (1) | AU5646396A (en) |
| CA (1) | CA2216854A1 (en) |
| CZ (1) | CZ330597A3 (en) |
| DE (1) | DE19515275A1 (en) |
| HR (1) | HRP960196A2 (en) |
| IL (1) | IL117844A0 (en) |
| MX (1) | MX9707735A (en) |
| NO (1) | NO974941D0 (en) |
| WO (1) | WO1996033727A1 (en) |
| ZA (1) | ZA963296B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE37913B1 (en) * | 1972-08-02 | 1977-11-09 | Bioresearch Sas | Salt of s-adenosyl-l-methionine |
| JPS59139319A (en) * | 1983-01-31 | 1984-08-10 | Fuji Kagaku Kogyo Kk | Remedy for body dysfunction caused by cerebral disorder |
| JPH02290896A (en) * | 1989-04-28 | 1990-11-30 | Fuji Kagaku Kogyo Kk | Novel s-adenosylmethionine derivative |
| DE4425280C2 (en) * | 1994-07-16 | 1997-05-07 | Knoll Ag | Use of (S) -denosyl-L-methionine and its physiologically tolerable salts for the treatment of reperfusion damage that is triggered after temporary focal ischemia |
-
1995
- 1995-04-26 DE DE19515275A patent/DE19515275A1/en not_active Withdrawn
-
1996
- 1996-04-08 IL IL11784496A patent/IL117844A0/en unknown
- 1996-04-13 AU AU56463/96A patent/AU5646396A/en not_active Abandoned
- 1996-04-13 MX MX9707735A patent/MX9707735A/en unknown
- 1996-04-13 WO PCT/EP1996/001570 patent/WO1996033727A1/en not_active Application Discontinuation
- 1996-04-13 KR KR1019970707585A patent/KR19990008061A/en not_active Application Discontinuation
- 1996-04-13 JP JP8532131A patent/JPH11504023A/en active Pending
- 1996-04-13 CN CN96193498A patent/CN1182367A/en active Pending
- 1996-04-13 CZ CZ973305A patent/CZ330597A3/en unknown
- 1996-04-13 CA CA002216854A patent/CA2216854A1/en not_active Abandoned
- 1996-04-13 EP EP96913500A patent/EP0822820A1/en not_active Withdrawn
- 1996-04-23 AR AR33625596A patent/AR001687A1/en unknown
- 1996-04-24 HR HR19515275.1A patent/HRP960196A2/en not_active Application Discontinuation
- 1996-04-25 ZA ZA9603296A patent/ZA963296B/en unknown
-
1997
- 1997-10-24 NO NO974941A patent/NO974941D0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR001687A1 (en) | 1997-11-26 |
| KR19990008061A (en) | 1999-01-25 |
| JPH11504023A (en) | 1999-04-06 |
| CA2216854A1 (en) | 1996-10-13 |
| MX9707735A (en) | 1997-12-31 |
| ZA963296B (en) | 1997-10-27 |
| IL117844A0 (en) | 1996-08-04 |
| NO974941L (en) | 1997-10-24 |
| NO974941D0 (en) | 1997-10-24 |
| EP0822820A1 (en) | 1998-02-11 |
| CZ330597A3 (en) | 1998-02-18 |
| CN1182367A (en) | 1998-05-20 |
| WO1996033727A1 (en) | 1996-10-31 |
| AU5646396A (en) | 1996-11-18 |
| DE19515275A1 (en) | 1996-10-31 |
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