Heparin chemical modification

Determination of Heparin. Chemical. Modifications of the methods of Warren and Wysocki (9) and Bassiouni (I) were used. Where plasma or blood was not involved, a direct titration of the heparin with azure A, either measuring the dye removal or redissolving the precipitate, was used. 

There can be little doubt that the isolation of a homogeneous heparin preparation is difficult. In fact, Jorpes considered that heparin is not a definite compound but a mixture of mucoitin polysulfates. He suggested that the isolation of a range of heparins with increasing sulfur content could be explained in two ways firstly, it is possible that heparin is elaborated and broken doivn in the body in such a way that heparins with different levels of activity exist side by side secondly, the purest form of heparin may undergo chemical modification during the isolation procedure, to yield less active materials. Jorpes favored the former alternative. 

It appears that some degree of chemical modification of heparin may be... 

Chemical modification of the unfiactionated heparin, such as desul tion, deamination and coupling with various agents have resulted in products of non-anticoagulant nature with selective actions on enzymes and cellular receptors. Thioxyloside derivatives have also been reported to produce oral antithrombotic actions in animal models. However, relatively larger dosages are needed to produce these effects. These heparin derivatives are currently tested for such indications as sepsis, viral infections and the treatment of proliferative disorders. 

To prepare A-propanoyl-, A-hexanoyl-, and A,0-quatemary substituted chitosan sulfate with the similar structure of heparin, the chemical modification of chitosan sulfate was carried out by Huang et al. (2003). The propanoyl (SCOS II) and hexanoyl (SCOS III) groups increased the thromboplastin time (APTT) activity, and the propanoyl groups also increased the thrombin time (TT) anticoagulant activity slightly, while the A,0-quaternary chitosan sulfate (SCOS IV) showed only a slight TT coagulant activity. 

Maksimenko, A. V, Petrova, M. L., Tischenko, E. G., and Schechilina, Y. V. (2001). Chemical modification of hyaluronidase regulates its inhibition by heparin. European Journal of Pharmaceutics and Biopharmaceutics 51, 33-38. 

Linhardt RJ (1992) Chemical and enzymatic methods for the depolymerization and modification of heparin. In Ogura H (ed) Carbohydrates—synthetic methods and application in medicinal chemistry. KodanshaWCH Publishers, Tokyo, p 387... 

Opsonization-induced polyplex disassembly during systemic circulation also represents a barrier to efficient cellular targeting. The instability of electrostatic polyelectrolyte assemblies means polyplexes are susceptible to polyanion displacement after cellular or chemical interaction, such as with erythrocytes or heparin, respectively. Increased levels of free polycations in the blood, and in particular high MW and nondegradable polymers, could induce adverse effects if excreted or broken down. However, there are numerous reports where surface modification of the polyplex with hydrophilic polymers leads to steric stability with reduction in disassembly during systemic circulation. " ... 

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