IL147477A - Preparation of medication comprising citicoline together with a second pharmaceutical agent for protecting brain tissue from infraction following ischemia - Google Patents
Preparation of medication comprising citicoline together with a second pharmaceutical agent for protecting brain tissue from infraction following ischemiaInfo
- Publication number
- IL147477A IL147477A IL147477A IL14747796A IL147477A IL 147477 A IL147477 A IL 147477A IL 147477 A IL147477 A IL 147477A IL 14747796 A IL14747796 A IL 14747796A IL 147477 A IL147477 A IL 147477A
- Authority
- IL
- Israel
- Prior art keywords
- citicoline
- agents
- ischemia
- therapeutic agent
- salt
- Prior art date
Links
- RZZPDXZPRHQOCG-OJAKKHQRSA-M CDP-choline(1-) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-M 0.000 title claims abstract 16
- 229960001284 citicoline Drugs 0.000 title claims abstract 16
- 239000003814 drug Substances 0.000 title claims 16
- 208000028867 ischemia Diseases 0.000 title claims 12
- 210000005013 brain tissue Anatomy 0.000 title claims 5
- 229940079593 drug Drugs 0.000 title 1
- 239000008177 pharmaceutical agent Substances 0.000 title 1
- 206010008118 cerebral infarction Diseases 0.000 claims abstract 8
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract 5
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract 3
- 206010019196 Head injury Diseases 0.000 claims abstract 3
- 208000006011 Stroke Diseases 0.000 claims abstract 3
- 229940124597 therapeutic agent Drugs 0.000 claims 13
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims 12
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 12
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 12
- 239000003795 chemical substances by application Substances 0.000 claims 10
- 150000003839 salts Chemical class 0.000 claims 10
- 239000000203 mixture Substances 0.000 claims 9
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims 7
- 229960001138 acetylsalicylic acid Drugs 0.000 claims 7
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- VOBNSQKMDIOJTQ-UHFFFAOYSA-N 2-aminoethyl phosphono hydrogen phosphate Chemical compound NCCOP(O)(=O)OP(O)(O)=O VOBNSQKMDIOJTQ-UHFFFAOYSA-N 0.000 claims 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims 4
- 239000003146 anticoagulant agent Substances 0.000 claims 4
- 230000000324 neuroprotective effect Effects 0.000 claims 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 2
- 102000004127 Cytokines Human genes 0.000 claims 2
- 108090000695 Cytokines Proteins 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 229940123457 Free radical scavenger Drugs 0.000 claims 2
- 108010023197 Streptokinase Proteins 0.000 claims 2
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 claims 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims 2
- 230000002253 anti-ischaemic effect Effects 0.000 claims 2
- 229940127090 anticoagulant agent Drugs 0.000 claims 2
- 229940127218 antiplatelet drug Drugs 0.000 claims 2
- 239000003633 blood substitute Substances 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 239000000480 calcium channel blocker Substances 0.000 claims 2
- 239000002872 contrast media Substances 0.000 claims 2
- 229960002768 dipyridamole Drugs 0.000 claims 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 229940088598 enzyme Drugs 0.000 claims 2
- 150000002270 gangliosides Chemical class 0.000 claims 2
- 239000005556 hormone Substances 0.000 claims 2
- 229940088597 hormone Drugs 0.000 claims 2
- 239000012216 imaging agent Substances 0.000 claims 2
- 239000003695 memory enhancer Substances 0.000 claims 2
- -1 neuroprotectives Substances 0.000 claims 2
- 239000002858 neurotransmitter agent Substances 0.000 claims 2
- 239000002664 nootropic agent Substances 0.000 claims 2
- 230000001777 nootropic effect Effects 0.000 claims 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims 2
- 239000002516 radical scavenger Substances 0.000 claims 2
- 229960005202 streptokinase Drugs 0.000 claims 2
- 230000002537 thrombolytic effect Effects 0.000 claims 2
- 229960005356 urokinase Drugs 0.000 claims 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract 2
- 206010061216 Infarction Diseases 0.000 abstract 1
- 230000007574 infarction Effects 0.000 abstract 1
- 230000000302 ischemic effect Effects 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention is directed to a method of reducing the extent of infarction, particularly cerebral infarction subsequent to cerebral ischemia, by the administration of citicoline shortly after an ischemic episode and continuing daily treatment for up to about 30 days, preferably for at least about 6 weeks. The method is useful in the treatment of stroke and severe head trauma patients and maximizes the chances for a full or substantially full recovery of the patient.
[US5872108A]
Claims (28)
1. A pharmaceutical composition, comprising: a) a therapeutically effective amount of citicoline or salt thereof; b) a therapeutically effective amount of a second therapeutic agent; and c) a pharmaceutically acceptable carrier; with the proviso that cytidine diphosphoethanolamine, cytidine diphospho-N-methylethanolamine, cytidine diphospho- N,N- dimethyl ethanolamine or mixtures thereof, are excluded.
2. A pharmaceutical composition- for protecting brain tissue from cerebral infarction subsequent to ischemia in a subject, comprising a) an amount of citicoline or salt thereof, that is effective in protecting brain tissue from cerebral infarction subsequent to ischemia in a subject; b) a therapeutically effective amount of a second therapeutic agent; and c) a pharmaceutically acceptable carrier; with the provision that cytidine diphosphoethanolamine, cytidine diphospho-N-methylethanolamine, cytidine diphospho-- N,Ndimethyl ethanolamine or mixtures thereof, are excluded.
3. The pharmaceutical composition of claim 2 wherein said amount of citicoline or salt thereof ranges from about Ί00 mg to about 4000 mg of citicoline and wherein said therapeutically effective amount of said second therapeutic agent is from about 10 mg to about 500 mg.
4. The pharmaceutical composition of claim 3 wherein said amount of citicoline or salt thereof ranges from about 100 mg to about 1000 mg of citicoline, wherein said second therapeutic agent is aspirin and wherein said therapeutically effective amount of said aspirin is from about 50 mg to about 500 mg.
5. The pharmaceutical composition of claim 4 wherein said therapeutically effective amount of said aspirin is from about 70 mg to about 300 mg.
6. The pharmaceutical composition of claim 4 wherein said amount of citicoline or salt thereof ranges from about 300 mgto about 700 mgof citicoline. 147477/5 34
7. The pharmaceutical composition of claim 4 wherein said amount of citicoline or salt thereof ranges from about 400 mg to about 600 mg of citicoline, "/'herein said second therapeutic agent is aspirin and wherein said therapeutically effective amount of said aspirin is from about 70 mg to about 90 mg.
8. The composition according to claim 2 wherein said ischemia occurs in the brain.
9. The composition according to claim 2 wherein said subject is a human.
10. The composition according to claim 2 wherein said subject has suffered a cerebral ischemia, head trauma or stroke.
11. 1 1. The composition of claim 1 or 2 wherein said second therapeutic agent is selected from a group consisting of antiplatelet agents, anticoagulant agents, thrombolytic and related agents, anti-ischemic agents, neuroprotectives, calcium channel blockers, agents targeted at nitric oxide, agents targeted at various neurotransmitters, cytokines, hormones and related products, free-radical scavengers, gangliosides and related products, modulators of various specific enzymes, memory enhancers or nootropics, neuroprotectives with diverse actions, haemorrheological agents and blood substitutes, imaging agents and contrast agents.
12. The composition of claim 1 or 2 wherein said second therapeutic agent is selected from a group consisting ofNMDA, t-PA, streptokinase, urokinase, aspirin and dipyridamole.
13. Use of citicoline or salt thereof, together with a second therapeutic agent in the manufacture of a medicament for protecting brain tissue from cerebral infarction subsequent to ischemia in a subject, with the proviso that cytidine diphosphoethanolamine, cytidine diphospho-N-methylethanolamine, cytidine diphospho-N,N-dimethylethanolamine or mixtures thereof, are excluded.
14. Citicoline or salt thereof, together with a second therapeutic agent for use as a medicament for the protection of brain tissue from cerebral infarction subsequent to ischemia in a subject, with the proviso that cytidine diphosphoethanolamine, cytidine diphospho-N-methylethanolamine, cytidine diphospho-N,N-dimethylethanolamine or mixtures thereof, are excluded.
15. The use of claim 13 or 14 wherein said second therapeutic agent is selected from a group consisting of antiplatelet agents, anticoagulant agents, thrombolytic and related agents, anti-ischemic agents, neuroprotectives, calcium channel blockers, agents targeted at nitric oxide, agents targeted at various neurotransmitters, cytokines, hormones and related products, free-radical scavengers, gangliosides and related products, modulators of various specific enzymes, memory enhancers or nootropics, neuroprotectives with diverse actions, haemorrheological agents and blood substitutes, imaging agents and contrast agents.
16. The use of claim 13 or 14 wherein said second therapeutic agent is selected from a group consisting of NMDA, t-PA, streptokinase, urokinase, aspirin and dipyridamole.
17. The use according to claim 14 within about 24 hours, after the occurrence of said ischemia.
18. The use according to claim 14 within about 12 to about 15 hours after the occurrence of said ischemia.
19. The use according to claim 14 for a period of at least about 30 days after the occurrence of said ischemia.
20. The use according to claim 14 for a period of at least about 4-8 weeks after the occurrence of said ischemia.
21. The use according to claim 14 for a period of at least about six months to about one year after the occurrence of said ischemia.
22. The use according to claim 13 or 14 wherein said ischemia occurs in the brain.
23. ■23. The use according to claim 13 or 14 wherein said subject is a human.
24. The use according to claim 13 or 14 wherein said subject has suffered a cerebral ischemia, head trauma or stroke. 147477/3 36
25. 2.5. The use according to claim 14 wherein said citicoline or salt thereof and said second therapeutic agent are used simultaneously.
26. The use according to claim 14 wherein said citicoline or salt thereof and said second therapeutic agent are used sequentially.
27. The pharmaceutical composition according to anyone of claims 1-12, substantially as herein described with reference to the examples and drawings.
28. The use according to anyone of claims 13-26, substantially as herein described with reference to the examples and drawings. g:\pctros20Q7\9006\l 8\aniended pages.doc/kh*
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39926295A | 1995-03-06 | 1995-03-06 | |
| US08/603,102 US5872108A (en) | 1995-03-06 | 1996-02-20 | Reduction of infarct volume using citicoline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL147477A true IL147477A (en) | 2010-02-17 |
Family
ID=23578854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL147477A IL147477A (en) | 1995-03-06 | 1996-03-05 | Preparation of medication comprising citicoline together with a second pharmaceutical agent for protecting brain tissue from infraction following ischemia |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US5872108A (en) |
| KR (1) | KR19980702724A (en) |
| IL (1) | IL147477A (en) |
| IN (1) | IN182555B (en) |
| ZA (1) | ZA961791B (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6002394A (en) * | 1995-10-02 | 1999-12-14 | Starsight Telecast, Inc. | Systems and methods for linking television viewers with advertisers and broadcasters |
| EP1041992A4 (en) * | 1997-12-24 | 2007-05-09 | Ferrer Int | Hyperhydrated citicoline, process and use |
| US6379882B1 (en) * | 1998-09-14 | 2002-04-30 | Elan Pharmaceuticals, Inc. | Method for selecting compounds for treating ischemia-related cellular damage |
| ES2169986B1 (en) | 2000-03-14 | 2003-06-16 | Ferrer Int | USE OF CDP-HILL FOR PROFILACTIC TREATMENT OF CEREBRAL ISCHEMIA. |
| US7235649B2 (en) * | 2000-03-24 | 2007-06-26 | Duke University | Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same |
| CA2429196A1 (en) * | 2000-03-24 | 2001-10-04 | Duke University | Characterization of grp94-ligand interactions and purification, screening, and therapeutic methods relating thereto |
| US7034054B2 (en) * | 2000-12-15 | 2006-04-25 | Galileo Pharmaceuticals, Inc. | Methods for the prevention and treatment of cerebral ischemia using non-alpha tocopherols |
| WO2003100570A2 (en) * | 2002-05-23 | 2003-12-04 | New England Medical Center Hospitals, Inc. | Computer-assisted multi-dimensional patient selection |
| CA2566612C (en) * | 2004-05-13 | 2015-06-30 | Massachusetts Institute Of Technology | Uridine effects on dopamine release |
| PT2471530T (en) | 2005-06-01 | 2017-04-19 | Edison Pharmaceuticals Inc | Redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomarkers |
| EP1986636B1 (en) | 2006-02-22 | 2013-04-24 | Edison Pharmaceuticals, Inc. | Phenol and 1,4-benzoquinone derivatives for use in the treatment of mitochondrial diseases |
| SI2470168T1 (en) * | 2009-08-26 | 2018-05-31 | Bioelectron Technology Corporation | Methods for the prevention and treatment of cerebral ischemia |
| JP2011178687A (en) * | 2010-02-26 | 2011-09-15 | Kochi Univ | Preventive and/or therapeutic agent for pain caused by hematopoietic cell transplantation |
| WO2012164563A1 (en) | 2011-06-01 | 2012-12-06 | Brain Watch Ltd. | Isotopically labeled cdp-choline and uses thereof |
| US10709767B2 (en) | 2012-05-31 | 2020-07-14 | Kinki University | Agent for prophylactic and/or therapeutic treatment of peripheral neuropathic pain caused by anticancer agent |
| WO2017106803A1 (en) | 2015-12-17 | 2017-06-22 | Bioelectron Technology Corporation | Flouroalkyl, flouroalkoxy, phenoxy, heteroaryloxy, alkoxy, and amine 1,4-benzoquinone derivatives for treatment of oxidative stress disorders |
| US11497795B2 (en) | 2018-09-28 | 2022-11-15 | Asahi Kasei Pharma Corporation | Medicament for mitigating conditions and/or suppressing onset of peripheral neuropathy induced by anti-malignant tumor agent |
| US20250002559A1 (en) * | 2023-06-28 | 2025-01-02 | Pharmazz, Inc. | Pharmaceutical formulation for treatment of cerebral stroke |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5517769B2 (en) * | 1972-01-10 | 1980-05-14 | ||
| US4386078A (en) * | 1980-03-03 | 1983-05-31 | The Ohio State University Research Foundation | Therapeutic agents for preventing phospholipid degradation and free fatty acid proliferation |
| IT1207106B (en) * | 1980-04-18 | 1989-05-17 | Made Italiana Srl Ora Searle I | PHARMACEUTICAL PREPARATION CONTAINING CITIDIN DISFOFOCOLINA ABSORBABLE ORALLY |
| JPS6043078B2 (en) * | 1980-10-31 | 1985-09-26 | 株式会社興人 | Production method of choline cytidine diphosphate |
| JPS57108099A (en) * | 1980-12-25 | 1982-07-05 | Kohjin Co Ltd | Preparation of choline cytidine diphosphate |
| JPS6043079B2 (en) * | 1980-12-25 | 1985-09-26 | 株式会社興人 | Method for producing choline cytidine diphosphate |
-
1996
- 1996-02-20 US US08/603,102 patent/US5872108A/en not_active Expired - Lifetime
- 1996-03-05 ZA ZA961791A patent/ZA961791B/en unknown
- 1996-03-05 IL IL147477A patent/IL147477A/en not_active IP Right Cessation
- 1996-03-06 KR KR1019970706131A patent/KR19980702724A/en not_active Ceased
- 1996-03-06 IN IN347MA1996 patent/IN182555B/en unknown
-
1997
- 1997-03-18 US US08/820,244 patent/US5801160A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR19980702724A (en) | 1998-08-05 |
| IN182555B (en) | 1999-05-01 |
| US5872108A (en) | 1999-02-16 |
| ZA961791B (en) | 1996-09-10 |
| US5801160A (en) | 1998-09-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| EXP | Patent expired |