Compounds having a retarding action on the coagulation of blood and processes of preparing the same

Abstract

Abstract Sulphuric acid esters of dextrane are prepared by subjecting dextrane, which may be partially hydrolysed, to the action of a sulphating agent, for example sulphur trioxide, concentrated sulphuric acid, oleum, sulphuryl chloride, N-pyridinium sulphonic or, preferably, chlorsulphonic acid. The esterification may vary from less than one esterified OH-group per glucose unit up to complete esterification. The acid esters may be partially or completely neutralized by means of a basic compound, preferably by alkali or alkaline earth bases. The salt or ester may be freed of sulphuric acid by dialysis, by precipitation of the salt or ester from aqueous solution with alcohol or by precipitating the sulphuric acid by means of Ca or Ba ions. The salts or esters may be used as anti-coagulating agents in the treatment of blood (see Group VI). In an example, a partially hydrolysed dextrane, prepared by boiling a 4 per cent aqueous dextrane solution with hydrochloric acid for 3 minutes followed by neutralization with caustic soda and precipitation as the sodium salt by addition of alcohol, was reacted with chlorsulphonic acid in anhydrous pyridine and the resulting sulphuric acid ester of dextrane precipitated by addition of alcohol. The ester was then dissolved in water, neutralized with caustic soda, the solution dialysed until free of sulphuric acid after which the sodium salt of the ester was precipitated by addition of alcohol. A suitable partially hydrolysed dextrane may also be of the kind disclosed in Specification 583,378.ALSO:In an example, a partially hydrolysed dextrane is prepared by boiling an aqueous solution of dextrane with concentrated hydrochloric acid for 3 minutes, the solution then being cooled and neutralised with caustic soda; the partially hydrolysed dextrane obtained is precipitated by addition of alcohol. Reference is made to the preparation of such dextrane disclosed in Specification 583,378, [Group IV].ALSO:Sulphuric acid esters of dextrane in the neutralised or unneutralised state (see Group IV) may be employed as agents for retarding the coagulation of blood. Preferably the esters are derived from partially hydrolysed dextrane of the kind disclosed in Specification 583,378 (as open to inspection under Sect. 91) [Group IV]. Salts of these esters, particularly of alkali or alkaline earth metals in water, saline solutions or other therapeutic fluids yield alone or in admixture with other physiologically suitable salts and therapeutic substances, solutions well adapted for intravenous injection. The degree of esterification of the dextrane may vary from a sulphur content below that of the mono-ester up to complete esterification while p the neutralisation may be partial or complete. An example describes the preparation of the sodium salt of the sulphur ester of a partially hydrolysed dextrane.

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