Relation of biological properties to chemical composition

Commercial heparin and heparinoid solutions commonly have phenol or tricresol added as a preservative. These are potent stimulants of isolated smooth muscle and pharmacological actions of heparin have been recorded due to the presence of these substances . Pharmacologically active agents have been reported developing from the reaction of phenol with material in heparin . 

It is very difficult to remove the last traces of such material from heparin, yet this can be pharmacologically active. The histamine found in heparin after acid hydrolysis, as in the determination of normal blood histamine, probably arises from such peptides. Heparinoids prepared from natural 

The presence of accompanying polysaccharides Heparinoids usually contain some of the original polysaccharide, while commercial heparin, as shown by the presence of anthrone-reducing substance, also usually contains such material. The elevation of body temperature, leucocytosis and thrombocytosis associated with pyrogens, can be due to the presence of extremely minute amounts of certain polysaccharides. One should suspect reactions of this nature as being due to traces of neutral polysaccharides. 

The presence of low molecular weight substances of unknown nature About 20 per cent by weight of heparin can be removed by prolonged dialysis of the heparinic acid . 

The distinction to be made between free and bound heparin probably relates to linkages with amino acids which are not salt linkages, and similar to those discussed for mucopolysaccharides. The involvement of zinc in the linkage of histamine to heparin in the mast cell indicates the possibility of various tertiary systems being important in biological activity, as originally proposed by A. Fischer. 

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