EP0939636A1 - Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromes - Google Patents
Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromesInfo
- Publication number
- EP0939636A1 EP0939636A1 EP97948977A EP97948977A EP0939636A1 EP 0939636 A1 EP0939636 A1 EP 0939636A1 EP 97948977 A EP97948977 A EP 97948977A EP 97948977 A EP97948977 A EP 97948977A EP 0939636 A1 EP0939636 A1 EP 0939636A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- thalidomide
- treatment
- disease
- parkinson
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Definitions
- the present invention relates to the application of thalidomide, its enantiomers and its polymorphic forms to the treatment of PARKINSON disease and parkinsonian syndromes.
- Thalidomide is known to be useful as a sedative and hypnotic (KUNTZ et al., Arzneiffen-Forsch., 6, 426-430 (1956); SALTER et al., J. Clin. Exper. Psychopath., 20, 243- 246 (1959)), for the treatment of skin lesions and ulcerations (W09524891), for the treatment of Alzheimer's disease (W09517154), for the treatment of insulin-resistant diabetes (W09517186), for the treatment of arthritis rheumatoid (WO9504533) and for the treatment of AIDS (WO9504525).
- thalidomide its enantiomers and its polymorphic forms are useful in the treatment of PARKINSON disease and parkinsonian syndromes.
- mice The activity of the products was therefore demonstrated in mice by measuring the decreases in the levels of striatal dopamine, 3,4-dihydroxy phenylacetic acid and homovanillic acid induced by MPTP compared with those of control animals.
- mice (C57BL / 6) weighing 20-25 g are injected 3 times at 2.5 hour intervals 15 mg / kg of MPTP intraperitoneally. Thirty minutes before the first MPTP injection, then 2 hours, 4 hours and 30 minutes and 7 hours after the first MPTP injection, 25 or
- mice 50 mg / kg of the product to be studied.
- the mice are sacrificed 24 hours after the last injection of MPTP.
- the striatum is dissected and stored at -70 ° C until the time of its analysis.
- the dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels are measured by high pressure liquid chromatography with electrochemical detection.
- Statistical analyzes are performed using ANOVA followed by the TUKEY KRAMER test.
- Thalidomide, its enantiomers and its polymorphic forms can be prepared according to the methods described in patent GB768821 and by J.C. REEPMEYER, Chirality, 1996, vol 8, 11-17; G. BLASCHKE et al., Arzneim. Forsch., 29, 1640 (1979); J.C. REEPMEYER et al., J. Chem.
- the medicaments according to the invention consist of thalidomide, a polymorphic form or one of its enantiomers, in the pure state or in the form of a composition in which it is associated with any other pharmaceutically compatible product, which may be inert or physiologically active.
- the medicaments according to the invention can be used orally, parenterally, rectally or topically.
- compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
- the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
- inert diluents such as starch, cellulose, sucrose, lactose or silica
- These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.
- compositions for oral administration there may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
- inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
- These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
- the sterile compositions for parenteral administration can preferably be aqueous or nonaqueous solutions, suspensions or emulsions.
- solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable.
- These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
- compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
- compositions for topical administration can be, for example, creams, lotions, mouthwashes, nasal drops or aerosols.
- the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 30 and 1000 mg and, preferably 100 and 400 mg, per day orally for an adult with unit doses ranging from 10 to 100 mg of active substance.
- the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
- Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique -Thalidomide 50 mg
- capsules containing 50 mg of active product having the following composition are prepared:
- a solution for injection containing 10 mg of active product having the following composition is prepared: - Thalidomide 10 mg
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention concerns the application of thalidomide, its enantiomers and its polymorphic forms to the treatment of PARKINSON'S disease and parkisonian syndromes.
Description
- -
APPLICATION DE LA THALIDOMIDE AU TRAITEMENT DE LA MALADIE DE PARKINSON ET DES SYNDROMES PARKINSONIENSAPPLICATION OF THALIDOMIDE TO THE TREATMENT OF PARKINSON'S DISEASE AND PARKINSONIAN SYNDROMES
La présente invention concerne l'application de la thalidomide, ses énantiomères et ses formes polymorphes au traitement de la maladie de PARKINSON et des syndromes parkinsoniens.The present invention relates to the application of thalidomide, its enantiomers and its polymorphic forms to the treatment of PARKINSON disease and parkinsonian syndromes.
Il est connu que la thalidomide est utile comme sédatif et hypnotique (KUNTZ et coll., Arzneimittel-Forsch., 6, 426-430 (1956); SALTER et coll., J. Clin. Exper. Psychopath., 20, 243-246 (1959)), pour le traitement des lésions et ulcérations de la peau (W09524891 ), pour le traitement de la maladie d'Alzheimer (W09517154), pour le traitement des diabètes insulinorésistants (W09517186), pour le traitement de l'arthrite rhumatoïde (WO9504533) et pour le traitement du SIDA (WO9504525).Thalidomide is known to be useful as a sedative and hypnotic (KUNTZ et al., Arzneimittel-Forsch., 6, 426-430 (1956); SALTER et al., J. Clin. Exper. Psychopath., 20, 243- 246 (1959)), for the treatment of skin lesions and ulcerations (W09524891), for the treatment of Alzheimer's disease (W09517154), for the treatment of insulin-resistant diabetes (W09517186), for the treatment of arthritis rheumatoid (WO9504533) and for the treatment of AIDS (WO9504525).
Il a maintenant été trouvé de manière surprenante que la thalidomide, ses énantiomères et ses formes polymorphes sont utiles dans le traitement de la maladie de PARKINSON et des syndromes parkinsoniens.It has now surprisingly been found that thalidomide, its enantiomers and its polymorphic forms are useful in the treatment of PARKINSON disease and parkinsonian syndromes.
Il est connu que la neurotoxine MPTP (1 -méthyl-4-phényl-1 ,2,3,6- tétrahydropyridine) induit un syndrome similaire à la maladie de Parkinson. Ce syndrome résulte d'une dégénération des neurones nigrostriataux dopaminergiques chez les primates (R. S. BURNS et coll., Proc. Natl. Acad. ScL, 80, 4546-4550 (1983), chez l'homme (J. W. LANGSTON et coll., Science, 219, 979-980 (1983)) et chez la souris (R. E. HEIKKILA et coll., Science, 224, 1451 -1453 (1984).It is known that the neurotoxin MPTP (1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine) induces a syndrome similar to Parkinson's disease. This syndrome results from a degeneration of nigrostriatal dopaminergic neurons in primates (RS BURNS et al., Proc. Natl. Acad. ScL, 80, 4546-4550 (1983), in humans (JW LANGSTON et al., Science , 219, 979-980 (1983)) and in mice (RE HEIKKILA et al., Science, 224, 1451 -1453 (1984).
L'activité des produits a donc été mise en évidence chez la souris en mesurant les diminutions des taux de dopamine striatale, d'acide dihydroxy-3,4 phénylacetique et d'acide homovanillique induites par la MPTP comparées à celles des animaux témoins.The activity of the products was therefore demonstrated in mice by measuring the decreases in the levels of striatal dopamine, 3,4-dihydroxy phenylacetic acid and homovanillic acid induced by MPTP compared with those of control animals.
On injecte, 3 fois à 2,5 heures d'intervalle, 15 mg/kg de MPTP par voie intrapéritonéale à des souris (C57BL/6) pesant 20-25 g. Trente minutes avant la première injection de MPTP, puis 2 heures, 4 heures et 30 minutes et 7 heures après la première injection de MPTP on administre 25 ouMice (C57BL / 6) weighing 20-25 g are injected 3 times at 2.5 hour intervals 15 mg / kg of MPTP intraperitoneally. Thirty minutes before the first MPTP injection, then 2 hours, 4 hours and 30 minutes and 7 hours after the first MPTP injection, 25 or
50 mg/kg du produit à étudier. Les souris sont sacrifiées 24 heures après la
dernière injection de MPTP. Le striatum est disséqué et conservé à -70°C jusqu'au moment de son analyse. Les taux de dopamine, d'acide dihydroxy- 3,4 phénylacetique et d'acide homovanillique sont mesurés par chromatographie liquide haute pression avec une détection électrochimique. Les analyses statistiques sont effectuées en utilisant ANOVA suivi par le test de TUKEY KRAMER.50 mg / kg of the product to be studied. The mice are sacrificed 24 hours after the last injection of MPTP. The striatum is dissected and stored at -70 ° C until the time of its analysis. The dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels are measured by high pressure liquid chromatography with electrochemical detection. Statistical analyzes are performed using ANOVA followed by the TUKEY KRAMER test.
Les résultats obtenus avec des doses de 25 et 50 mg/kg de thalidomide sont mentionnés dans le tableau suivant:The results obtained with doses of 25 and 50 mg / kg of thalidomide are mentioned in the following table:
Ces résultats montrent que la thalidomide s'oppose aux diminutions des taux de dopamine et d'acide homovanillique induites par la MPTP dans le striatum. These results show that thalidomide is opposed to the decreases in dopamine and homovanillic acid levels induced by MPTP in the striatum.
La thalidomide, ses énantiomères et ses formes polymorphes peuvent être préparés selon les procédés décrits dans le brevet GB768821 et par J.C. REEPMEYER, Chirality, 1996, vol 8, 11 -17; G. BLASCHKE et coll., Arzneim. Forsch., 29, 1640 (1979); J.C. REEPMEYER et coll., J. Chem.Thalidomide, its enantiomers and its polymorphic forms can be prepared according to the methods described in patent GB768821 and by J.C. REEPMEYER, Chirality, 1996, vol 8, 11-17; G. BLASCHKE et al., Arzneim. Forsch., 29, 1640 (1979); J.C. REEPMEYER et al., J. Chem.
Soc, Perkin trans 2, 2063 (1994).Soc, Perkin trans 2, 2063 (1994).
Les médicaments selon l'invention sont constitués par la thalidomide, une forme polymorphe ou un de ses énantiomères, à l'état pur ou sous forme d'une composition dans laquelle elle est associée à tout autre produit pharmaceutiquement compatible, pouvant être inerte ou physiologiquement actif. Les médicaments selon l'invention peuvent être employés par voie orale, parentérale, rectale ou topique.The medicaments according to the invention consist of thalidomide, a polymorphic form or one of its enantiomers, in the pure state or in the form of a composition in which it is associated with any other pharmaceutically compatible product, which may be inert or physiologically active. The medicaments according to the invention can be used orally, parenterally, rectally or topically.
Comme compositions solides pour administration orale, peuvent être utilisés des comprimés, des pilules, des poudres (capsules de gélatine, cachets) ou des granulés. Dans ces compositions, le principe actif selon l'invention est mélangé à un ou plusieurs diluants inertes, tels que amidon, cellulose, saccharose, lactose ou silice, sous courant d'argon. Ces compositions peuvent également comprendre des substances autres que les diluants, par exemple un ou plusieurs lubrifiants tels que le stéarate de magnésium ou le talc, un colorant, un enrobage (dragées) ou un vernis.As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.
Comme compositions liquides pour administration orale, on peut utiliser des solutions, des suspensions, des émulsions, des sirops et des élixirs pharmaceutiquement acceptables contenant des diluants inertes tels que l'eau, l'éthanol, le glycérol, les huiles végétales ou l'huile de paraffine. Ces compositions peuvent comprendre des substances autres que les diluants, par exemple des produits mouillants, édulcorants, épaississants, aromatisants ou stabilisants.As liquid compositions for oral administration, there may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin. These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
Les compositions stériles pour administration parentérale, peuvent être de préférence des solutions aqueuses ou non aqueuses, des
suspensions ou des émulsions. Comme solvant ou véhicule, on peut employer l'eau, le propylèneglycol, un polyéthylèneglycol, des huiles végétales, en particulier l'huile d'olive, des esters organiques injectables, par exemple l'oléate d'éthyle ou d'autres solvants organiques convenables. Ces compositions peuvent également contenir des adjuvants, en particulier des agents mouillants, isotonisants, émulsifiants, dispersants et stabilisants. La stérilisation peut se faire de plusieurs façons, par exemple par filtration aseptisante, en incorporant à la composition des agents stérilisants, par irradiation ou par chauffage. Elles peuvent également être préparées sous forme de compositions solides stériles qui peuvent être dissoutes au moment de l'emploi dans de l'eau stérile ou tout autre milieu stérile injectable.The sterile compositions for parenteral administration can preferably be aqueous or nonaqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable. These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
Les compositions pour administration rectale sont les suppositoires ou les capsules rectales qui contiennent, outre le produit actif, des excipients tels que le beurre de cacao, des glycérides semisynthétiques ou des polyéthylèneglycols.The compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
Les compositions pour administration topique peuvent être par exemple des crèmes, lotions, collutoires, gouttes nasales ou aérosols.The compositions for topical administration can be, for example, creams, lotions, mouthwashes, nasal drops or aerosols.
Les doses dépendent de l'effet recherché, de la durée du traitement et de la voie d'administration utilisée; elles sont généralement comprises entre 30 et 1000 mg et, de préférence 100 et 400 mg, par jour par voie orale pour un adulte avec des doses unitaires allant de 10 à 100 mg de substance active.The doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 30 and 1000 mg and, preferably 100 and 400 mg, per day orally for an adult with unit doses ranging from 10 to 100 mg of active substance.
D'une façon générale, le médecin déterminera la posologie appropriée en fonction de l'âge, du poids et de tous les autres facteurs propres au sujet à traiter.In general, the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
Les exemples suivants illustrent des médicaments selon l'invention :The following examples illustrate medicaments according to the invention:
Exemple AExample A
On prépare, selon la technique habituelle, des comprimés dosés à 50 mg de produit actif ayant la composition suivante
-Thalidomide 50 mgTablets containing 50 mg of active product having the following composition are prepared according to the usual technique -Thalidomide 50 mg
- Mannitol 64 mg- Mannitol 64 mg
- Cellulose microcristalline 50 mg- Microcrystalline cellulose 50 mg
- Polyvidone excipient 12 mg - Carboxyméthylamidon sodique 16 mg- Polyvidone excipient 12 mg - Carboxymethyl starch sodium 16 mg
- Talc 4 mg- Talc 4 mg
- Stéarate de magnésium 2 mg- Magnesium stearate 2 mg
- Silice colloïdale anhydre 2 mg- Anhydrous colloidal silica 2 mg
- Mélange de méthylhydroxypropylcellulose, polyéthylèneglycol 6000, dioxyde de titane (72-3,5-24,5) q.s.p. 1 comprimé pellicule terminé à 245 mg- Mixture of methylhydroxypropylcellulose, polyethylene glycol 6000, titanium dioxide (72-3,5-24,5) q.s.p. 1 film-coated tablet finished at 245 mg
Exemple BExample B
On prépare, selon la technique habituelle, des gélules dosées à 50 mg de produit actif ayant la composition suivante :Using the usual technique, capsules containing 50 mg of active product having the following composition are prepared:
-Thalidomide 50 mg-Thalidomide 50 mg
- Cellulose 18 mg- Cellulose 18 mg
- Lactose 55 mg- Lactose 55 mg
- Silice colloïdale 1 mg- Colloidal silica 1 mg
- Carboxyméthylamidon sodique 10 mg - Talc 10 mg- Carboxymethyl starch sodium 10 mg - Talc 10 mg
- Stéarate de magnésium 1 mg- Magnesium stearate 1 mg
Exemple CExample C
On prépare une solution injectable contenant 10 mg de produit actif ayant la composition suivante : - Thalidomide 10 mgA solution for injection containing 10 mg of active product having the following composition is prepared: - Thalidomide 10 mg
- Acide benzoïque 80 mg- Benzoic acid 80 mg
- Alcool benzylique 0,06 cm3- Benzyl alcohol 0.06 cm3
- Benzoate de sodium 80 mg- Sodium benzoate 80 mg
- Ethanol à 95 % 0,4 cm3 - Hydroxyde de sodium 24 mg- 95% ethanol 0.4 cm3 - Sodium hydroxide 24 mg
- Propylène glycol 1 ,6 cm3- Propylene glycol 1.6 cm3
- Eau q.s.p. 4 cm3
- Water q.s.p. 4 cm3
Claims
REVENDICATIONS
1 - Application de la thalidomide, ses énantiomères et ses formes polymorphes pour obtenir un médicament destiné au traitement de la maladie de PARKINSON et des symptômes parkinsoniens.1 - Application of thalidomide, its enantiomers and its polymorphic forms to obtain a medicament intended for the treatment of PARKINSON disease and parkinsonian symptoms.
2 - Application selon la revendication 1 pour obtenir un médicament comprenant 10 à 100 mg de thalidomide.
2 - Application according to claim 1 for obtaining a medicament comprising 10 to 100 mg of thalidomide.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9614936A FR2756737B1 (en) | 1996-12-05 | 1996-12-05 | APPLICATION OF THALIDOMIDE TO THE TREATMENT OF PARKINSON'S DISEASE AND PARKINSONIAN SYNDROMES |
| FR9614936 | 1996-12-05 | ||
| PCT/FR1997/002175 WO1998024433A1 (en) | 1996-12-05 | 1997-12-02 | Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0939636A1 true EP0939636A1 (en) | 1999-09-08 |
Family
ID=9498364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP97948977A Withdrawn EP0939636A1 (en) | 1996-12-05 | 1997-12-02 | Application of thalidomide to the treatment of parkinson's disease and parkisonian syndromes |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0939636A1 (en) |
| JP (1) | JP2001505215A (en) |
| AU (1) | AU7622798A (en) |
| FR (1) | FR2756737B1 (en) |
| WO (1) | WO1998024433A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2833850B1 (en) | 2001-12-26 | 2004-01-23 | Look Fixations Sa | DEVICE FOR MOUNTING A FIXING ELEMENT USED ON A SLIDING BOARD |
| FR2834904B1 (en) | 2002-01-21 | 2004-02-20 | Look Fixations Sa | SLIDING BOARD AND REMOVABLE PIECE FORMING A COVER FOR MOUNTING ON SUCH A BOARD |
| US20050143344A1 (en) * | 2003-12-30 | 2005-06-30 | Zeldis Jerome B. | Methods and compositions using immunomodulatory compounds for the treatment and management of central nervous system disorders or diseases |
| US20050182097A1 (en) * | 2003-12-30 | 2005-08-18 | Zeldis Jerome B. | Methods and compositions using thalidomide for the treatment and management of central nervous system disorders or diseases |
| JP5339588B2 (en) * | 2008-11-10 | 2013-11-13 | 国立大学法人 新潟大学 | A therapeutic drug for schizophrenia containing thalidomide or its derivatives as an active ingredient |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0712310A1 (en) * | 1993-08-04 | 1996-05-22 | Andrulis Pharmaceuticals Corporation | Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection |
| US5434170A (en) * | 1993-12-23 | 1995-07-18 | Andrulis Pharmaceuticals Corp. | Method for treating neurocognitive disorders |
-
1996
- 1996-12-05 FR FR9614936A patent/FR2756737B1/en not_active Expired - Fee Related
-
1997
- 1997-12-02 AU AU76227/98A patent/AU7622798A/en not_active Abandoned
- 1997-12-02 JP JP52527398A patent/JP2001505215A/en active Pending
- 1997-12-02 WO PCT/FR1997/002175 patent/WO1998024433A1/en not_active Application Discontinuation
- 1997-12-02 EP EP97948977A patent/EP0939636A1/en not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9824433A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7622798A (en) | 1998-06-29 |
| FR2756737B1 (en) | 1999-01-08 |
| WO1998024433A1 (en) | 1998-06-11 |
| FR2756737A1 (en) | 1998-06-12 |
| JP2001505215A (en) | 2001-04-17 |
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