WO1999004793A2 - Budipine in the treatment of inflammatory disorders of the nervous system - Google Patents

Abstract

The invention relates to a novel use of the active ingredient budipine (INN) in the treatment of inflammatory disorders of the nervous system.

Description

Budipin in the treatment of inflammatory diseases of the nervous system

Technical field

The invention relates to the new use of the active ingredient budipin (INN) in the treatment of inflammatory diseases of the nervous system.

State of the art

British patent 1313781 describes substituted piperidines which are said to have a long-lasting, centrally stimulating effect. One of the active substances covered by the British patent, for which the INN Budipin was later recommended, is used in the treatment of Parkinsonism. - It is also known from the prior art (WO96 / 31208) that budipin should be suitable for the treatment of sigma-receptor-modulated diseases.

Description of the invention

Surprisingly, it has now been found that budipin inhibits the formation of the tumor necrosis factor α (TNF-α) and interleukin-6 (II-6).

The invention therefore relates in a first aspect to the use of budipin in the treatment of inflammatory diseases of the nervous system.

Another object of the invention is the use of budipin in the manufacture of medicaments for the treatment of inflammatory diseases of the nervous system.

For the purposes of the invention, the term budipin means not only the compound 1-tert-butyl-4,4-diphenylpiperidine, but also its pharmacologically acceptable salts. Preferred salts are all pharmacologically acceptable acid addition salts with the inorganic and organic acids commonly used in galenics. Suitable as such are water-soluble and water-insoluble acid addition salts with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, maleic acid Malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, the acids used in salt production - depending on whether it is a mono- or polybasic acid and depending on which salt is desired - be used in an equimolar or a different quantity ratio. Among the inflammatory diseases of the nervous system, for the treatment of which Budipin can be used, multiple sclerosis should be mentioned first.

When using budipin according to the invention for the production of the above-mentioned medicinal products, budipin or a salt thereof (= the active ingredient) with suitable pharmaceutical auxiliaries or carriers is converted into tablets, dragées, capsules, suppositories, plasters (for example as a transdermal therapeutic system = TTS), emulsions , Suspensions or solutions are processed, the active ingredient content advantageously being between 0.1 and 95% and the galenic dosage form (for example a slow release form or a dosage form) which is precisely adapted to the active ingredient and / or the desired onset of action by the appropriate choice of auxiliaries and carriers enteric form) can be achieved.

The person skilled in the art is familiar with the auxiliaries and excipients suitable for the desired pharmaceutical formulations on the basis of his specialist knowledge. In addition to solvents, gel formers, suppository bases, tablet excipients and other active substance carriers, for example antioxidants, dispersants, emulsifiers, defoamers, taste correctives, preservatives, solubilizers, colorants or, in particular, permeation promoters and complexing agents (e.g. cyclodextrins) can be used.

The active ingredient can be administered orally, rectally, parenterally or percutaneously.

In general, it has proven to be advantageous in human medicine to give the active ingredient when administered orally in a daily dose of about 0.1 to about 3, in particular 0.4 to 1.0, mg / kg of body weight, optionally in the form of several, preferably 1 to To administer 3 single doses to achieve the desired result, whereby a dosing in and out has proven to be advantageous. In the case of parenteral treatment, similar or generally lower doses (in particular when the active ingredient is administered intravenously) can be used. The optimum dosage and type of application of the active ingredient required in each case can easily be determined by any person skilled in the art on the basis of his specialist knowledge.

If budipin or a salt thereof is to be used for the treatment of inflammatory diseases of the nervous system, the pharmaceutical preparations can also contain one or more pharmacologically active constituents of other groups of medicaments.

The invention further comprises the use of budipin for the treatment of inflammatory diseases of the nervous system. Investigations carried out

Mononuclear cells from 3 healthy blood donors were isolated, suspended (10 ^δ / ml) and at 37 ° C in buffered (25mM HEPES) RPMI medium with the addition of 10% fetal calf serum as well as L-glutamine and gentamycin in the presence of 10 ^{" 7} mol / l, 10 ^"8 mol / l, 10 ^{" 9} mol / l and without (= control) budipin. After 48 hours of culture, the supernatants were removed, centrifuged and stored at -80 ° C. until examination. Each test was carried out The cytokine content was determined in duplicate using commercially available ELISA determination sets for TNF-α and II-6 (Quantikine, R&D Systems, DPC Biermann GmbH, Bad Nauheim, Germany). The results are shown in the table below which result in inhibition of TNF-α and II-6 formation.

table

Inhibition of TNF-α and II-6 release from mononuclear cells by budipin

SEM = standard error of the mean (n = 9)

Claims

claims 1. Use of Budipin and its salts in the manufacture of medicines for the treatment of inflammatory diseases of the nervous system. 2. Use of budipin hydrochloride in the manufacture of medicines for the treatment of inflammatory diseases of the nervous system. 3. Use of Budipin and its salts for the treatment of inflammatory diseases of the nervous system. 4. Use of budipin hydrochloride for the treatment of inflammatory diseases of the nervous system. 5. Use according to one of claims 1 to 4, characterized in that it is multiple sclerosis in the inflammatory diseases of the nervous system. 6. Use of Budipin and its salts in the manufacture of tablets with an active substance content between 5 mg and 100 mg Budipin for the treatment of multiple sclerosis.