IL31486A - Composition for the treatment of pathologically increased muscle tone containing a furazan derivative - Google Patents

Description

Composition for the treatment of pathologically increased muscle tone containing a furazan derivative The present invention concerns a new composition for the treatment of pathologically increased muscle tone in it has been that is a good central muscle relaxant and anticonvulsant having a high therapeutic It is a valuable active substance for compositions which can be to relieve pathologically increased muscle tone caused by rheumatic spondylitis or disc itself and the production thereof have been described in the literature Angelico and 63662 The muscle relaxant effect is ascertained pharmacologically by various Determination of the inhibition of the pinna and corneal A characteristic of the central muscle relaxants is the abolition of the pinna reflex after administration of fairly small quantities of active whereas the corneal reflex can only be abolished after much higher Procedure reflexes are determined in white mice weighing 18 25 The pinna reflex and the corneal reflex are tested by stroking the external auditory or touching the cornea with a nylon The dosage is determined at which the pinna reflex and corneal reflex are abolished in of the The mice are not fed for 12 hours before the beginning of the The test substance is by mouth 1 hour before the The is ascertained by interpolation of che probability graph and Schiill s Cornea about 600 1C00 g Determination of the inhibition of the monosynaptic patellar tendon reflex and of the polysynaptic flexor Procecure Tracheotomy is performed on cats weighing kg under anaesthesia 55 as a solution in The test substance in propylene glycol solution is injected within 3 minutes into the jugular Patellar tendon After the femur has been the contraction of the quadriceps muscle of the right hind leg is induced by hitting the an automatic hammer at 10 second contraction is recorded The change in amplitude is determined as a related the amplitude of the muscle contractions before administration of the Flexor The of the tibialis anterior muscle of the left hind leg are recorded isotonically after submaximal electrical stimulation of the central of the severed n tibial Subrnaximal rectangular current duration 2 voltage The interval between is The change in amplitude is determined in percent related to the amplitude the muscle contractions before administration of the dosage cnange in Patellar tendon about Flexor refle 19 Determination of the anticonvulsant effect by of electroshock the rat characteristic property of the central relaxants is This of the test substance can be as Male white rats weighing g used for the The electrodes are applied to the external An alternating current of of 100 V is for the electroshock and the stimulation lasts The test substance is administered by mouth 1 hour before the dose which prevents tonic convulsions z legs in the animals is ascertained by interpolation on Result abuut 25 The acute toxicity of the test compound is a single administration by in male an The period is The is and R Acute The acute toxicity is also in male and female rabbits weighing The test is tered in 5 solution in 100 propylene A speed of injection is 1 ml in 30 Result Acute about 100 The daily dosages of the active substance vary and 6C00 mg for adult patients of normal For dosages reduced according to their weight Suitable dosage units such as dragees coated suppositories and preferably tain 15 1000 rng of the Dosage units for oral administration preferably contain between 60 of as active To tablets or dragee the active substance is with pulverulent carriers such as potato also laminar powder or citrus pulp optionally with the additio of lubricants and binders such as highly dispersed silicic magnesium or calcium stearic polyethylene glycols or gelatin or cellulose derivatives such as ethyl cellulose and sodium salt of carboxymethyl Dragee cores are then with concentrated sugar solutions which can also gum talcum titanium or with a lacquer dissolved in easily volatile organic solvents or mixtures of Dyes tuf s can be added of active Other suitable units oral administra ion are hard gelatine capsules as well as soft capsules of gelatine and a softener such as The hard capsules preferably contain the active substance in the form of a granulate in admixture with diluents such as saccharose or lubricants such as talcum or magnesium s earate stabilisers such as sodium or In soft the active substance is preferably dissolved or suspended in suitable liquids such as liquid polyethylene glycols or to which stabilisers can also be Dosage units which are also suitable for oral administration pastilles prepared with the usual Examples of dosage units for rectal administration are suppositories which consist of a combination with a suppository natural or synthetic or also gelatine rectal capsules a combination of the active substance with polyethylene glycols or Dosage units for parenteral administra on ly contain 1 active and a solubility promoter or The following for can be used as solubility promoters or e propylene sodium or the sodium salt of a water soluble salts of bile acids such as sodium morpholine ethanolamine sitol phosphatide preparations and lecithin preparations a poor oil optionally together wi partial polyoxyethylene The following examples illustrate the production of different forms for administration but they by no means limit the scope of the invention in any Example 1 To produce each which contains 500 mg of active kg of are with kg of dried potato The mass obtained is moistened kg of stearic acid in litres of ethanol and the whole is mixed for kg of gelatine in l litres of distilled water are then added the mass is kneeded for 20 As soon as it is sufficiently it is granulated through a sieve mes and The dried granulate is again sieved and is then mixed for 1 hour with kg of potato kg of talcum and kg of sodium carboxymethyl The mass obtained is pressed into each of which weighs To each of which mg of as active kg of active substance with kg of lactose and kg of highly dispersed The mixture is moistened with a granulating liquid heated to consisting of kg of kg of glycerin and litres of The moist mixture is granulated through a suitable sieve sieve The granulate is then dried for 8 hours in a drying oven at or in a drier for about at and then sieved through a suitable sieve sieve The granulate is then mixed with kg of and kg of starch and 300 g of magnesium the mixture is pressed into dragee cores each of which weighs 6 3 To produce capsules each of active g of are mixed g of talcum and g of magnesium stearate and the is sieved through a sieve sieve whereupon it is evenly filled into capsules of size Example 4 Suppositories are prepared by mixing 750 g of furazan with kg of adeps solidus and then form ing 1000 suppositories of g each containing 750 mg of insufficientOCRQuality

Claims (1)

1. CLAIMS therapeutic compositions for producing muscle relaxant and anticonvulsive effects comprising a pharmaceutical carrier and a therapeutically effective amount of Compositions according to Claim being in dosage unit form acceptable for internal For the Applicants insufficientOCRQuality