WO1995004525A2 - Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection - Google Patents
Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection Download PDFInfo
- Publication number
- WO1995004525A2 WO1995004525A2 PCT/US1994/008741 US9408741W WO9504525A2 WO 1995004525 A2 WO1995004525 A2 WO 1995004525A2 US 9408741 W US9408741 W US 9408741W WO 9504525 A2 WO9504525 A2 WO 9504525A2
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- WO
- WIPO (PCT)
- Prior art keywords
- inhibitor
- composition
- reverse transcriptase
- thalidomide
- tnf
- Prior art date
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- 0 CC([C@@](C*)(C=C)C=CC(C(*1)=CCc2c1cccc2)=O)=O Chemical compound CC([C@@](C*)(C=C)C=CC(C(*1)=CCc2c1cccc2)=O)=O 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
Definitions
- the present invention relates to de novo compositions of matter for the treatment of AIDS.
- the present invention further relates to the de novo compositions of m& er containing TNF inhibitors and antiviral agents selected from the group of reverse transcriptase inhibitors, protease inhibitors, gene inhibitors (of such genes as gag, env, tat, rev, and pol), myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- a drug should give a patient a lasting cure, or at least improve the condition of the patient having a particular disease while causing minimal side effects.
- Latest advances in drug research rely on the systematic research and further understanding of the disease process at the molecular level.
- HIV Human Immunodeficiency virus
- AIDS Acquired Immunodeficiency Syndrome
- the most widely accepted therapeutic composition for treating AIDS is the compound azidothymidine, also known as AZT.
- Recent discoveries relating to AIDS have implicated tumor necrosis factor as a stimulatory agent in the growth of HIV.
- Tumor necrosis factor inhibitors which have been studied in the past include thalidomide, pentoxifylline and xanthine derivatives.
- TNF tumor necrosis factor
- Antiviral therapy such as therapy for Human Immunodeficiency Virus
- Viruses are basically subcellular particles that can live only as intracellular parasites. They basically consist of a genome of RNA or DNA (single or double stranded), packaged inside a protein, and in some cases, with a lipid envelope covering the whole particle. Additionally, these particles infect cells, and replicate within the infected cell using much of the host cell apparatus needed to synthesize macromolecules (e.g., DNA, RNA, protein).
- TNF inhibitor is administered to a patient with other pharmaceutical compounds such as reverse transcriptase inhibitors, gene inhibitors, and HIV protease inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- other pharmaceutical compounds such as reverse transcriptase inhibitors, gene inhibitors, and HIV protease inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- compositions of matter and uses which include tumor necrosis factor inhibitors together with anti- AIDS agents, reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines and in combined formulations therewith.
- a further object of the present invention is a method for the therapeutic treatment of HIV infections by administering concurrently a combination of a tumor necrosis factor inhibitor and one or more compounds selected from the group consisting of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- the present invention deals with compositions of matter useful for therapeutic treatment of HIV and being a combination of tumor necrosis factor inhibitors and a compound selected from the group consisting of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell- virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- the preferred compounds which are used as tumor necrosis factor inhibitors are thalidomide, pentoxifylline, and xanthine derivatives.
- Some of the preferred reverse transcriptase inhibitors include azidothymidine (AZT), dideoxy inosine (ddl), dideoxycytidine (ddC), fluorodideoxythymidine (FddT), as well as other compounds such as D4T, FddT 3TC, BI-RG-587, R-82150 and L697639 whose structures are shown below.
- reverse transcriptase inhibitors include:
- the preferred compounds which would act as gene inhibitors would be benzodiazepine derivatives.
- One promising agent which inhibits the tat gene is RO-24-7429 which is a benzodiazepine shown below.
- the preferred inhibitors of myristoylation would be:
- the preferred inhibitors of cell-virus binding include:
- the preferred inhibitors of LTR promoter sites would include:
- Triplex-forming oligonucleotide • Strand 3B of triplex forming oligonucleotide
- the preferred inhibitors of platelet aggregation would include:
- the preferred ribosome inactivators would include:
- the preferred prophylactic and therapeutic HIV vaccines would be:
- the present invention presents a method of treating HIV by combination therapy which includes administering a tumor necrosis factor inhibitor and, independently, a compound selected from the group of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- a tumor necrosis factor inhibitor and, independently, a compound selected from the group of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
- Example 1 200 milligrams of thalidomide are mixed with 400 milligrams of AZT. The active ingredients are triturated and Q.S. with lactose to selected capsule size.
- thalidomide 200 milligrams of thalidomide are mixed with 500 milligrams of ddl.
- the active ingredients are triturated and Q.S. with lactose to selected capsule size.
- Example 3 300 milligrams of thalidomide are mixed with 500 milligrams of ddC.
- the active ingredients are triturated and Q.S. with lactose to selected capsule size.
- Example 4 200 milligrams of pentoxifylline are mixed with 500 milligrams of AZT. The active ingredients are triturated and Q.S. with lactose to selected capsule size. Example 5.
- pentoxifylline 300 milligrams of pentoxifylline are mixed with 500 milligrams of ddl.
- the active ingredients are triturated and Q.S. with lactose to selected capsule size.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A pharmaceutical composition comprising: (a) a tumor necrosis factor inhibitor; (b) a compound selected from the group consisting of reverse transcriptase inhibitor, protease inhibitor, a gene inhibitor, myristoylation inhibitor, cell-virus binding inhibitor, LTR promoter site inhibitor, ribosome inactivators, platelet aggregation inhibitor and prophylactic and therapeutic HIV vaccine, and (c) a pharmaceutical inert nontoxic carrier are described.
Description
USE OF TUMOR NECROSIS FACTOR INHIBITORS TOGETHER
WITH ANTIVIRAL AGENTS AND THERAPEUTIC
COMPOSITIONS THEREOF AGAINST HIV INFECTION
The present invention relates to de novo compositions of matter for the treatment of AIDS. The present invention further relates to the de novo compositions of m& er containing TNF inhibitors and antiviral agents selected from the group of reverse transcriptase inhibitors, protease inhibitors, gene inhibitors (of such genes as gag, env, tat, rev, and pol), myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
DESCRIPTION OF THE PRIOR ART
Under ideal circumstances, a drug should give a patient a lasting cure, or at least improve the condition of the patient having a particular disease while causing minimal side effects. Latest advances in drug research rely on the systematic research and further understanding of the disease process at the molecular level. Over the last few years there has been an enormous amount of research directed toward Human Immunodeficiency virus (HIV), which causes Acquired Immunodeficiency Syndrome (AIDS). At the present time, the most widely accepted therapeutic composition for treating AIDS is the compound azidothymidine, also known as AZT. Recent discoveries relating to AIDS have implicated tumor necrosis factor as a stimulatory agent in the growth of HIV. Because tumor necrosis factor has been implicated as a factor in AIDS, there has been a need to look at tumor necrosis factor inhibitors of those diseases. Tumor necrosis factor inhibitors which have been studied in the past include thalidomide, pentoxifylline and xanthine derivatives.
Within the context of the present specification, when applicant refers to tumor necrosis factor (TNF) it is meant to signify TNF-a, TNF -p or mixtures thereof. Antiviral therapy such as therapy for Human Immunodeficiency Virus,
is the subject of vigorous research all over the world. Viruses are basically subcellular particles that can live only as intracellular parasites. They basically consist of a genome of RNA or DNA (single or double stranded), packaged inside a protein, and in some cases, with a lipid envelope covering the whole particle. Additionally, these particles infect cells, and replicate within the infected cell using much of the host cell apparatus needed to synthesize macromolecules (e.g., DNA, RNA, protein). A large number of progeny then leave the cell, often by causing it to burst. The viral progeny then infect other cells and these processes repeat over and over again. Because HIV shares many host functions for replication, the possibility of interfering with his life cycle was initially considered remote. But proteins specific to the functioning of the virus have now been identified. At the present level of research, it is possible to design molecules which interfere with these viral functions with acceptable or bearable toxic side effects. Because of the recent implications of tumor necrosis factor in the development of HIV1, it would appear desirable to combine therapeutic methods wherein a TNF inhibitor is administered to a patient with other pharmaceutical compounds such as reverse transcriptase inhibitors, gene inhibitors, and HIV protease inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines. The prior art is silent regarding compositions of matter and uses which include tumor necrosis factor inhibitors together with anti- AIDS agents, reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines and in combined formulations therewith.
SUMMARY OF THE INVENTION
The primary objects of the present invention are to provide pharmaceutical compositions containing a tumor necrosis factor inhibitor and an HIV reverse transcriptase inhibitor and to administer both independently. Another object of the present invention is to provide pharmaceutical compositions containing a tumor necrosis factor inhibitor and a HIV protease inhibitor.
An additional object of the present invention is to provide compositions of matter comprising a tumor necrosis factor inhibitor and an HIV gene inhibitor. Still another object of the present invention is to provide compositions of matter comprising tumor necrosis factor inhibitors and non-nucleoside reverse transcriptase inhibitors.
A further object of the present invention is a method for the therapeutic treatment of HIV infections by administering concurrently a combination of a tumor necrosis factor inhibitor and one or more compounds selected from the group consisting of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
DESCRD?TION OF THE PREFERRED EMBODIMENT
The present invention deals with compositions of matter useful for therapeutic treatment of HIV and being a combination of tumor necrosis factor inhibitors and a compound selected from the group consisting of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell- virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
The preferred compounds which are used as tumor necrosis factor inhibitors are thalidomide, pentoxifylline, and xanthine derivatives.
Some of the preferred reverse transcriptase inhibitors include azidothymidine (AZT), dideoxy inosine (ddl), dideoxycytidine (ddC), fluorodideoxythymidine (FddT), as well as other compounds such as D4T, FddT 3TC, BI-RG-587, R-82150 and L697639 whose structures are shown below.
D4T FddT Bl - RG - 587
L - 697639
3TC R - 82150 (& analogs: 696229, 697661)
Other reverse transcriptase inhibitors include:
• Lipophilic prodrug of AZT
• Bis-heteroaryl/piperazine U88ZO4E
Some of the preferred HIV-protease inhibitors which can be used as part of this invention are described structurally below.
• KN1-227 and KNl-272-transition state mimetic tripeptides
• SC52151
The preferred compounds which would act as gene inhibitors would be benzodiazepine derivatives. One promising agent which inhibits the tat gene is RO-24-7429 which is a benzodiazepine shown below.
24 - 7429 and R05 - 3335 analog (tat)
• TAR antisense transcript encoded in adeno-associated virus expression vector (tat)
• Mutant HIV expression vector (rev)
The preferred inhibitors of myristoylation would be:
• AC2, a synthetic phospholipid
The preferred inhibitors of cell-virus binding include:
• EL, a synthetic amino derivative of ether phospholipids
• Recombinant g l20 + MF59 adjuvant vaccine • Recombinant gpl60 + MF59/MTP-PE adjuvant vaccine
• Recombinant soluble CD4
• gpl20 peptide-PPD
The preferred inhibitors of LTR promoter sites would include:
• Triplex-forming oligonucleotide • Strand 3B of triplex forming oligonucleotide
The preferred inhibitors of platelet aggregation would include:
• Dipyridamole
The preferred ribosome inactivators would include:
• GLQ223 -purified trichosanthin
The preferred prophylactic and therapeutic HIV vaccines would be:
• recombinant gpl20 + MF59 adjuvant vaccine
• recombinant gpl60 + MF59/MTP-PE vaccine
• recombinant gp 160 vaccine
• gpl20 peptide-PPD
Therapeutically, the present invention presents a method of treating HIV by combination therapy which includes administering a tumor necrosis factor inhibitor and, independently, a compound selected from the group of reverse transcriptase inhibitors, HIV protease inhibitors, gene inhibitors, myristoylation inhibitors, cell-virus binding inhibitors, LTR promoter site inhibitors, ribosome inactivators, platelet aggregation inhibitors, platelet aggregation inhibitors and prophylactic and therapeutic HIV vaccines.
The following preferred examples are described below. However, they are representative without departing from the spirit of the invention or scope of the subject matter.
Example 1. 200 milligrams of thalidomide are mixed with 400 milligrams of AZT. The active ingredients are triturated and Q.S. with lactose to selected capsule size.
Example 2.
200 milligrams of thalidomide are mixed with 500 milligrams of ddl. The active ingredients are triturated and Q.S. with lactose to selected capsule size.
Example 3. 300 milligrams of thalidomide are mixed with 500 milligrams of ddC.
The active ingredients are triturated and Q.S. with lactose to selected capsule size.
Example 4. 200 milligrams of pentoxifylline are mixed with 500 milligrams of AZT. The active ingredients are triturated and Q.S. with lactose to selected capsule size.
Example 5.
300 milligrams of pentoxifylline are mixed with 500 milligrams of ddl. The active ingredients are triturated and Q.S. with lactose to selected capsule size.
The foregoing description is offered primarily for purposes of illustration. It will be readily apparent to those skilled in the art that numerous variations in both the formulations and their method of use, not mentioned above, may be made without departing from the spirit and scope of the invention.
Claims
1. A pharmaceutical composition comprising: (a) a tumor necrosis factor inhibitor; (b) a compound selected from the group consisting of reverse transcriptase inhibitors, protease inhibitor, a gene inhibitor, myristoylation inhibitor, cell-virus binding inhibitor, LTR promoter site inhibitor, ribosome inactivator, platelet aggregation inhibitor and prophylactic and therapeutic HIV vaccine, and (c) a pharmaceutical inert nontoxic carrier.
2. The composition of claim 1 wherein said tumor necrosis factor inhibitor is selected from the group consisting of thalidomide, pentoxifylline and xan thine derivatives.
3. The composition of claim 1 wherein said reverse transcriptase inhibitor is selected from the group consisting of AZT, ddl and ddC.
4. The composition of claim 2 wherein said tumor necrosis factor inhibitor is thalidomide.
5. The composition of claim 3 wherein said reverse transcriptase inhibitor is AZT.
6. The composition of claim 1 wherein said tumor necrosis factor inhibitor is thalidomide and said reverse transcriptase inhibitor is AZT.
7. The composition of claim 1 wherein said tumor necrosis factor inhibitor is pentoxifylline and said reverse transcriptase inhibitor is AZT.
8. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is ddl.
9. The composition of claim 1 wherein said TNF inhibitor is pentoxifylline and said reverse transcriptase inhibitor is ddl.
10. The composition of claim 2 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is ddC.
11. The composition of claim 1 wherein said TNF inhibitor is pentoxifylline and said reverse transcriptase inhibitor is ddC.
12. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said gene inhibitor is the tat inhibitor RO-24-7429.
13. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said myristoylation inhibitor is AC2.
14. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is lipophilic prodrug of AZT.
15. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is FddT.
16. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is D4T.
17. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is 3TC.
18. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is BI-RG-587.
19. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is R-82150.
20. The composition of claim 1 wherein said TNF inhibitor is thalidomide and said reverse transcriptase inhibitor is L697639.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP94922777A EP0712310A1 (en) | 1993-08-04 | 1994-08-03 | Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection |
| AU73763/94A AU7376394A (en) | 1993-08-04 | 1994-08-03 | Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10175293A | 1993-08-04 | 1993-08-04 | |
| US08/101,752 | 1993-08-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1995004525A2 true WO1995004525A2 (en) | 1995-02-16 |
| WO1995004525A3 WO1995004525A3 (en) | 1995-06-01 |
Family
ID=22286225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/008741 WO1995004525A2 (en) | 1993-08-04 | 1994-08-03 | Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0712310A1 (en) |
| AU (1) | AU7376394A (en) |
| WO (1) | WO1995004525A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997032587A1 (en) * | 1996-03-04 | 1997-09-12 | Dana-Farber Cancer Institute | Methods for treating viral infections |
| WO1998024433A1 (en) * | 1996-12-05 | 1998-06-11 | Rhone-Poulenc Rorer S.A. | Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromes |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009203A1 (en) * | 1990-11-21 | 1992-06-11 | Smithkline Beecham Corporation | Tnf inhibitors |
| WO1992014455A1 (en) * | 1991-02-14 | 1992-09-03 | The Rockefeller University | METHOD FOR CONTROLLING ABNORMAL CONCENTRATION TNF α IN HUMAN TISSUES |
-
1994
- 1994-08-03 EP EP94922777A patent/EP0712310A1/en not_active Withdrawn
- 1994-08-03 WO PCT/US1994/008741 patent/WO1995004525A2/en not_active Application Discontinuation
- 1994-08-03 AU AU73763/94A patent/AU7376394A/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009203A1 (en) * | 1990-11-21 | 1992-06-11 | Smithkline Beecham Corporation | Tnf inhibitors |
| WO1992014455A1 (en) * | 1991-02-14 | 1992-09-03 | The Rockefeller University | METHOD FOR CONTROLLING ABNORMAL CONCENTRATION TNF α IN HUMAN TISSUES |
Non-Patent Citations (5)
| Title |
|---|
| BLOOD, vol.77, no.8, 1991 pages 1653 - 1656 FATEMEH FAZELY ET AL. 'Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells' * |
| INT. CONF. AIDS, vol.8, no.2, 1992 page A57 ZHANG LIN ET AL. 'Pentoxifylline (Trental) enhances the antiretroviral activity of didanosine (dideoxyinosine, ddI)' * |
| INT.J.CLIN.PHARMACOL.THER.TOXICOL., vol.31, no.7, 1993 pages 343 - 350 D.R.LUKE ET AL. 'Phase I/II study of pentoxifylline with zidovudine on HIV-1 growth in AIDS patients' * |
| J.INTERN.MED., vol.228, no.6, 1990 pages 549 - 556 M.ODEH 'The role of tumor necrosis factor-alpha in acquired immunodeficiency syndrome' * |
| REV.INV.CLIN., vol.44, no.2, 1992 pages 285 - 286 GUILLERMO J. RUIZ-ARG]ELLES ET AL. 'La pentoxifyllina en el tratamiento de SIDA' * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997032587A1 (en) * | 1996-03-04 | 1997-09-12 | Dana-Farber Cancer Institute | Methods for treating viral infections |
| WO1998024433A1 (en) * | 1996-12-05 | 1998-06-11 | Rhone-Poulenc Rorer S.A. | Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromes |
| FR2756737A1 (en) * | 1996-12-05 | 1998-06-12 | Rhone Poulenc Rorer Sa | APPLICATION OF THALIDOMIDE TO THE TREATMENT OF PARKINSON'S DISEASE AND PARKINSONIAN SYNDROMES |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0712310A1 (en) | 1996-05-22 |
| WO1995004525A3 (en) | 1995-06-01 |
| AU7376394A (en) | 1995-02-28 |
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