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
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
  • A61K31/52—Purines, e.g. adenine
• • 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
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
  • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• • 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

Definitions

• the invention relates to the use of pentoxifylline for the treatment of the relapsing or chronically progressive form of multiple sclerosis.
• MS Multiple sclerosis
• the well-known clinical picture of MS includes the disseminated foci of desmarking in the patient's central nervous system (CNS). This demyelination spreads unsystematically in batches in the CNS and leads to the so-called flare-ups of nervous disorders that characterize the symptoms of the disease.
• CNS central nervous system
• the disease can only be treated symptomatically when the relapses occur with new neurological symptoms by administering corticosteroids (1 g / day iv over 3 days), which leads to a shortening of the relapse duration. Due to the known, numerous and serious side effects of the corticoids, however, preventive continuous therapy cannot be carried out with them. In addition, the treatment of patients who also have other diseases to be influenced by corticosteroids, e.g. B. Type I diabetes mellitus, extremely difficult and risky. In order to avoid these disadvantages, various drug groups were examined for their effectiveness.
• interferon-beta Studies on continuous therapy of MS with immunosuppressants such as azathioprine or cyclosporin A have been shown to have no effects on the course of the disease. In contrast, subcutaneous administration of interferon-beta was able to show a significant reduction in thrust for the first time. However, this application of interferon beta is difficult for the patient to handle, has numerous side effects and is very cost-intensive. In addition, interferon beta only works in those patients in whom the MS symptoms initially appear reluctantly.
• the object on which the invention is based is surprisingly achieved by the use of pentoxifylline in the therapy of the batchwise or chronically progressive form of MS.
• Pentoxifilyl is known to first of all have a positive effect on the deformability of erythrocytes and leukocytes. It is therefore mainly used to improve the microcirculation in angiopathies (J. of Medicine, Vol. 10, No. 5, 1979) or in general in peripheral arterial circulatory disorders and immune disorders. Secondly, it is known that pentoxifilline reduces platelet aggregation, promotes the release of prostacyclin I, and lowers mitotic rates of lymphomas. It is therefore used to prevent metastasis and in lymphoma therapy (J. of Medicine, Vol. 15, No. 5 and 6, 1984). A further indication for this use of pentoxifylline is experimental peritonitis, the administration of which leads to significantly less abscess formation and fibrin deposition (Are. Sog. Vol. 120, pp. 1141-1144, 1985).
• PTX in addition to the previously known indications, is suitable for the treatment of multiple sclerosis, without the frequently occurring side effects associated with other therapies.
• pentoxifylline first experiences in relapsing treatment with pentoxifylline were found. Both the intravenous treatment (3 x 200 mg iv / day for 5 days) and the oral therapy (3 to 4 x 400 mg / day) showed a significant reduction in the duration of the relapse and an increase in the relapse-free interval.
• the dose of pentoxifylline to be used is based on the general condition and the weight of the patient. It is generally 0.01 to 6 g / day, preferably 1 to 3 g / day and very particularly preferably 1.2 to 2.4 g / day. Based on kg of body weight, the concentrations used are 0.1 to 120 mg / (day kg), preferably 10 to 60 mg / (day kg) and very particularly preferably 12 to 48 mg / (day kg).
• prednisone In addition to other therapeutically used corticosteroids, prednisone, prednisolone, prednisolone-21-acetate, prednylidene and methyl prednisone are particularly suitable. Methylprednisolone is preferably used.
• the dosage is 0.01 to 10 mg / day, preferably 10 to 250 mg / day and very particularly preferably 100 to 200 mg / day. In single youngsters of mg per
• doses are preferably prepared which correspond to the doses most preferred, for example 1.2 mg / day PTX (16 mg / kg day PTX) orally and 500 mg / day Methylprednisolone (7 mg / kg day, iv) over 3 days. This amount is significantly lower than the doses previously administered in acute relapse therapy (1 g / day iv over 3 days). The lower doses significantly reduce the risk of a temporary diabetic metabolism, as is often observed with the previously used doses, with identical therapy success.
• the dose units of both the pure PTX preparations and the combinations with corticosteroids can be in the form of tablets, dragées, capsules or sustained-release formulas.
• the capsule material takes on the function of the carrier and the contents, for . B. may be present as a powder, gel, emulsion, etc.
• preparations for transdermal or parenteral i.p., i.v., i.m., subcutaneous
• Inhalation preparations spray preparations
• suppositories can also be used.
• Possible dosages are 200, 400 or 600 mg PTX / tablet or 100 or 300 mg PTX / ampoule; for the corticosteroids 0.5 to 10 mg / tablet or 10 to 1000 mg / ampoule.
• a female patient (42 years, 64 kg body weight) has been suffering from relapsing MS for eight years. In previous relapses, she was treated with corticosteroids, but this has led to psychosis several times. The patient was admitted with brainstem symptoms (double images, crippled paresthesias in the trigeminal area and gross nystagmus with dizziness and nausea). A new focus was found in the brainstem in magnetic resonance imaging. A 5-day infusion treatment with PTX (3 x 200 mg / day i.v.) was carried out. Already on the second day the patient felt a clear improvement in the vertigo symptoms and the double vision. After two days, nystagmus and tendency to fall were no longer clinically detectable. After the infusion therapy, the patient was switched to oral medication of 3 x 400 mg / day. No further relapses have occurred since then (6 months). Before the treatment, the patient had three to four relapses per year.
• a female patient (45 years, 58 kg body weight) has been suffering from MS for three years. So far, there have been predominantly sensitive symptoms, which had manifested themselves particularly in unpleasant paraesthesia of the extremities. During another relapse with excruciating, burning sensations on both legs, the patient was treated with 3 x 400 mg PTX / day. The dysaesthesia, which usually lasted for weeks, was reduced to such an extent after only three days that the patient was able to sleep again and to carry out her daily household chores. Here too there is now a 5-month follow-up period during which no further complaints have occurred.
• Example 3 Example 3:

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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 1993
  • 1993-12-16 DE DE4343034A patent/DE4343034C1/de not_active Expired - Fee Related
• 1994
  • 1994-12-16 JP JP7516543A patent/JPH09506603A/ja active Pending
  • 1994-12-16 CA CA002176848A patent/CA2176848A1/en not_active Abandoned
  • 1994-12-16 CZ CZ961708A patent/CZ170896A3/cs unknown
  • 1994-12-16 PL PL94314588A patent/PL314588A1/xx unknown
  • 1994-12-16 SK SK766-96A patent/SK76696A3/sk unknown
  • 1994-12-16 EP EP95904491A patent/EP0734262A1/de not_active Withdrawn
  • 1994-12-16 WO PCT/EP1994/004188 patent/WO1995016450A1/de not_active Ceased
  • 1994-12-16 FI FI962473A patent/FI962473A7/fi unknown
• 1996
  • 1996-06-13 NO NO962503A patent/NO962503D0/no unknown

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