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

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• 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)

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• 1996
  • 1996-12-05 FR FR9614936A patent/FR2756737B1/fr not_active Expired - Fee Related
• 1997
  • 1997-12-02 EP EP97948977A patent/EP0939636A1/de not_active Withdrawn
  • 1997-12-02 WO PCT/FR1997/002175 patent/WO1998024433A1/fr not_active Application Discontinuation
  • 1997-12-02 AU AU76227/98A patent/AU7622798A/en not_active Abandoned
  • 1997-12-02 JP JP52527398A patent/JP2001505215A/ja active Pending

Non-Patent Citations (1)

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