Patent GB-831096-A (GB)
Title: Cyanacethydrazide derivatives and compositions containing them
Inventor: GREENHALGH NORMAN
IPC: A61K31/635
Filed: 1956-12-20
Abstract: The invention comprises compounds of the formula CNCH2CONHNHCOOR (wherein R is a hydrocarbon radical of more than 2 carbon atoms) and their preparation either by interaction of cyanacethydrazide, which may be generated in situ from hydrazine and ethyl cyanacetate, with an appropriate haloformic ester, conveniently in an aqueous medium in presence of an acid-binding agent such as an alkali metal acetate, hydroxide, carbonate or bicarbonate or in an organic liquid such as pyridine, or by interaction of a cyanacetyl halide, a cyanacetic ester, cyanacetazide or cyanacetic acid with an appropriate ester of carboxyhydrazine, the reaction with cyanacetyl halide being conveniently conducted in a solvent such as ether, that with a cyanacetic ester being preferably performed by heating the reactants in vacuo, and that with cyanacetazide conveniently being conducted in an inert diluent such as a mixture of ether and water. Examples are given, in which R has the values of n-propyl, iso-propyl, n-butyl, iso-amyl, benzyl and phenyl.  The Provisional Specification describes the process of the invention in somewhat wider terms.ALSO:Pharmaceutical compositions, stated to be useful in the control of lungworm infestations in domestic livestock and also stated to have antitubercular activity, comprise as active ingredient not less than 0.01% by weight of at least one compound of the formula CNCH2CONHNHCOOR (wherein R is an hydrocarbon radical of more than two carbon atoms) in admixture with or in solution in suitable diluents or carriers.  Suitable compositions are injectable sterile aqueous solutions or suspensions or sterile non-aqueous solutions or suspensions, advantageously containing between 1 and 30% of the active ingredients and optionally containing other injectable ingredients of known therapeutic utility, such as antibacterial agents, e.g. sulphadimidine and stable penicillin preparaations, or an anthelmintic drug, e.g. 1-diethylcarbamoyl - 4 - methylpiperazine dihydrogen citrate. The aqueous solutions or suspensions may contain a stabilizing agent, e.g. sodium metabisulphite, in the proportion of 0.05 to 5% by weight of the composition, dispersing agents and anti-flocculation agents.  Suitable vehicles for the non-aqueous compositions include propylene glycol and polyethylene glycol and injectable vegetable oils such as arachis oil, olive oil and coconut oil.  The injectable compositions may also contain bacteriostatic agents such as phenyl mercuric acetate or nitrate, chlorocresol or long chain quaternary salts, e.g. hexadecyltrimethylammonium bromide. The pharmaceutical compositions also include those suitable for oral administration and these may also contain other compounds of known therapeutic utility such as, in addition to those referred to above, phenothiazine, hexachloroethane, piperazine or other piperazine derivatives or salts such as tripiperazine dicitrate.  Diluents suitable for use in these oral preparations include water, milk, chalk, kaolin, talc, urea, lactose and sodium chloride or sulphate, and livestock feeding stuffs such as crushed oats, barley meal, fish meal, linseed meal, ground nut meal and silage, advantageously present in about 90% by weight of the total weight of the composition.  Other adjuvants referred to are dispersing agents, e.g. phenol-ethylene oxide condensation products, formaldehyde - naphthalene sulphonic acid condensation products and fatty esters of polyglycerol, and anti-caking agents such as calcium phosphate. Preparations in the form of powders, premixes, tablets, capsules, nuts and pellets are also referred to. Examples describe compositions containing 2-carbo-n-butoxycyanacethydrazide in admixture with (1) sterile water with or without sodium metabisulphite and/or polyethylene glycol 400; (2) arachis oil; and (3) sulphadimidine, disodium methylenebis - naphthalene - 2 - sulphonate, polyglyceryl ricinoleate and water.