IL25630A - Pharmaceutical and veterinary compositions containing 2-amino-adamantane or salts thereof - Google Patents

Description

848 The invention relates to new pharmaceutical and veterinary a method for the preparation a method of animals treating with said compositions and to the preparation of the active In spite of the fact that in the last few decades a large number of drugs have become the mischief caused by infectious diseases is still For the World Health Organisation consider influenza as one of the infectious diseases which have to be combated owing to its high morbidity and resulting mortalityi the surplus mortality in the due to influenza A in the epidemic of 1 is estimated at 000 that of influenza B in at 57 000 Surplus mortality is understood to mean herein the number of dead which occurs in excess of the standard mortality which is the mortality to be expected on the basis of the mortality in preceding The serious results of influenza can be prevented to a great extent by means of not everybody can be treated with vaccins because some people are hypersensitive to for example hen which are present in the vaccins as a result of their A difficulty in composing vaccins is that influenza is caused by a great number of which mutually differ more or less serologically and that it cannot be said with certainty beforehand which strain will the vaccins must contain all those virus strains with which infection is In the various strains in the vaccin must be present in a sufficiently large quantity since otherwise the protection 848 and the seriousness of the local reactions at the point of injection increase Another possibility of combating virus for example is the regular administration of The investigation into similar agents is always aimed at finding substances which are active against a great number of gically and virologically differing This is because as already it cannot be foretold with certainty which virus infection will occur and because with one agent protection is desired against all virus infections which may possibly The most frequently occuring strains are those the and the She morbidity which was caused in 1 43 to by said viruses may be illustrated with reference to the following in which the percentage of patients in the American military forces is shown together with the virus strain which caused the An indication of the economic which were suffered 848 In this graph the average percentage of absenteeism per period 1 and the average frequencies of absenteeism per period per 100 workers 2 is specified men and women It appears from the table and the graph that the results of infections are of the same order of magnitude as those of From a publication in Pt 1 1 it is known that has antiviral stated It is that the substance may be used to cbmbate influenza viruses of the but that strains are insensitive to the Quite unexpectedly it was now found that as well as its salts have antiviral In addition it has surprisingly been found that and its salts are not only as active against strains as but in addition have a strong activity against B In the substances have the property which is particular importance for prophylactic use that they also exert their activity after oral administration as has been found in mouse The compounds are active inter alia against A and In addition to a strong activity against influenza A and B strains the compounds from tissue culture experiments also prove to have an interesting activity against influenza measles and mouse In agreement herewith the invention relates to ceutical and veterinary compositions characterized in that in addition to one or more solid or liquid carriers they contain a content of or a salt 2207 and in 151 As salts are to be considered formed with ceutically acceptable acids for example hydrochloric maleic sulphuric acetic fumaric acid nitric phosphoric citric lactic cyclohexylsulphonic acid succinic acid tartaric benzoic salicylic gluconic tannic acid and gallic The sulphuric acid salt is preferred because of several In contrast with the hydrochloric acid which is very the sulphuric acid salt is nearly not bitter at Also in contrast with the chloric acid salt the sulphuric acid salt does not cause corrosion of the tabletting Further the sulphuric acid salt is only to a slight extent soluble in which is a very important property in the preparation of After having been brought in a suitable mode of tration the and salts thereof may be used for trolling virus and notably preventing virus fections In agreement herewith the invention also relates to a in method of controlling virus characterized in that a composition is administered having a content of or a salt The administration of compositions according to the invention to human beings or animals may be started as soon as a virus infection has manifested Good results are obtained in particular when the administration of the composition is already started as soon as infection threatens or as soon as the wheather conditions render an early infection It is therefore recommandable to administer a daily dose during the winter months to protect against and its salts may both be injected and be administered orally or rectally but the Children may be treated with half a Animals may be treated for example a dose of from 10 to 100 preferably a and i1s salts may be processed mannergr to pharmaceutical and veterinary compositions such as coated injection liquids and if required with the addition of other drugs vitamins flavouring substances pigmentation In agreement herewith the invention also relates to a method of preparing pharmaceutical and veterinary characterized in that or a salt thereof is dissolved in or mixed with the commonly used liquid or solid if required together with other drugs vitamins flavouring substances pigmentation As carriers may be for calcium lactose and powdered sugar or mixtures of these The use of sugars as carriers has the advantage that said substances have a pleasant Tablets and coated tablets may contain in addition swelling agents which cause the preparation to disintegrate readily in As such may be for potato maize arrow root carboxy methyl In addition lubricants may be such as magnesium stearate and calcium As preservatives may be added such as and benzyl As substances may be for or triesters for lauric palmitic stearic ricinolic oleic acid with a polyalcohol such as and glycerol and in addition polyoxyethylene derivatives of inter alia the said salts from amino the salts of may be prepared reacting with an The reaction may be carried out in that the acid in question is added to a solution of or by adding to a solution of the However are not preferred since they may lead to Anclusion of the or the in the crystals of the In the case the salt of a solid acid has to be prepared the reaction is preferably carried out in that a solution of the combined base and a solution of an acid In the case the two solvents are immiscible the reaction takes place when the mixture is The reaction may be carried out at room but also at elevated or at lowered As suitable solvents may be mentioned ethers such as diethylether alcohols such as ethylalcohol hydrocarbons such as benzene and petroleum In order that the invention may readily carried into effect it will now be described in greater detail with reference to the ensuing specific Suspension for 100 gs of gs of 0 gs of gs of sodium chloride gs of polysorbate 80 water to 1000 200 mgs of 335 s of lactose 5 mgs of magnesium stearate mgs of 200 mgs of oxalic acid mgs of suppository of gs of 0 20 gs of benzoate and gs of sodium chloride were dissolved in 500 mis of boiling water for Another 300 mis of water for injection were added to the solution after which it was cooled to A solution of 4 gs of polysorbate 80 in water for injection of was added to the resulting The mixture was stirred until a homogeneous liquid was obtained and then cooled to The pH was adjusted to 6 with 0 1 hydrochloric acid after which the mixture was completed to 1000 ml with water for The solution was filtered through a Jena glass sterilized in an autoclave 30 minutes at 1 and cooled to room temperature while stirring and under aseptic 100 gs of having a particle size of from 1 10 were sterilized by dry heating at 1 for 1 After cooling the substance was suspended in 800 mis of the liquid prepared according to the above The suspension was completed to 1000 mis with the same stirred until a geneous solution had been obtained and dispensed in 200 gs of 335 gs of lactose and 30 gs of potato starch were mixed until a homogeneous mixture was The mixture was wetted with a 10 solution of gelatin in The moist mass was granulated and dried at after which the mass was granulated The granules were then mixed with gs of of stearate and gs of potato The resulting The preparation of coated tablets was carried out in the same manner as that of tablets with the difference that no flat but biconvex blets were made which were provided with a sugar layer and a glazing 200 gs of acid sieved through a 100 mesh sieve were while to 1500 gs of suppository mass heated to After a homogeneous paste had been obtained the mixture was dispensed in 1 suppository acetate To a solution of gs in 10 ml diethylether glacial acetic acid was dropped while The acetate pitated immediately and was subsequently filtered off by The salt was dried the Melting point in vacuo fumarate A saturated solution of 280 mgs fumaric acid in 2 mis ethanol was added a solution of gs in 10 mis ether while The fumarate precipitated and was filtered off and dried the Melting point hosphate A solution of gs in 250 mis diethylether was shaken with of an aqueous solution of phosphoric The phosphate precipitated and was subsequently filtered off and in Melting point above nitrate A solution of gs in 2 0 mis diethylether was shaken with 200 mis 1N aqueous nitric acid The nitrate began to The solution was concentrated in and the precipitate was filtered off and subsequently dried at the citrate To a solution of mgs in 2 ml diethylether a solution of 12 mgs citric acid in 2 mis 1 1 was The citrate precipitated and was filtered The in salt was dried the Melting point benzoate To 2 mis diethylether containing mgs mgs benzoic acid dissolved in 2 mis diethylether was The salt in was filtered off and dried the It consisted 0 of fine needles that converted into rods on heating at The rods melted at tartrate 30 mgs dissolved in 2 mis diethylether was added to a solution of 1 tartaric acid in 2 mis of a mixture 5 sisting of equal parts diethylether and The salt was subsequently filtered off and dried at the Melting point sulfate A solution of gs in 6 mis diethylether 0 was shaken with 10 mis of an aqueous solution containing 2 6 sulfuric The sulfate precipitated and was filtered off after that the solvent had been partly removed in The compound was dried at the Melting point 331 gallate 5 gallic acid dissolved in 3 mis diethylether was added to 30 mgs in 2 mis The salt that in pitated was filtered off and dried the Melting point insufficientOCRQuality

Claims (1)

CLAIMS Pharmaceutical is that in addition to one more solid or liquid carriers they hare a content of or a salt Veterinary characterised in that in addition to one or more solid or carriers they a content of or a salt Compositions as in Claim 1 or characterized in that they contain as the active A method of preparing pharmaceutical and veterinary characterized in that or a salt thereof ie dissolved in or mixed with one or more liquid or solid if required together with other drugs flavouring substances pigmentation A as claimed Claim characterized in that a tablet is A method as claimed in Claim characterised in that a coated tablet is A method of combating virus in characterized that a preparation is administered as claimed in
1. Claim 1 or A method as claimed in Claim characterized in that a composition is administered orally having a content of adamantane or salt A method of controlling virus infections in characterized in that or a salt thereof processed in a veterinary composition is administered in a A method as in Claim characterized in that or a salt thereof processed in a veterinary composition is administered in a daily dose of per lie A method as claimed in any of the preceding characterized in that is as the active A of preparing pharmaceutical and veterinary compositions according to 1 to substantially as herein described with to the specific Pharmaceutical according to Claim substantially as herein Veterinary compositions according to 2 t substantially as herein insufficientOCRQuality