Blood anticoagulants heparin sulfate

Sulfate diesters of chitin have been widely prepared because of their possible use as synthetic, blood anticoagulants. The sulfating reagent commonly used is chlorosulfonic acid in pyridine, but, more recently, chloro-sulfonic acid in 1,2-dichloroethane has been employed. Chitin disulfates can show up to 20 % of the anticoagulant potency of heparin, accompanied, in general, by only slight toxicity. ... 

In the case of pyridine-SOs, advantage has been taken of its combined ability to sulfamate and to sulfate in numerous attempts to duplicate synthetically the potent naturally occurring blood anticoagulant heparin. 

It is known that sulfated polysaccharides, including natural and synthesized ones, had great blood-compatibility or even anticoagulant activity [34]. After sulfation of sodium alginate, its derivative contains both sulfate and carboxyl groups, whose chemical structure is analogous to the natural blood anticoagulant heparin. Fan et al. 

Numerous other polysaccharides are known, such as gum arabic and other gums and mucilages, chondroitin sulfate (found in cartilage), the blood anticoagulant heparin (found in the liver and heart), and the dextrans (used as blood plasma substitutes). 

The anticoagulant heparin is a polysaccharide sulfate which can form an electrostatic complex with blood-clotting factors (see ASIDE on blood clotting) and prevent the cascade from progressing. 

Pig Blood. Collect a 100-200-ml blood sample in a sterile container with cap containing 750 units of heparin sulfate (anticoagulant) and 25-50- 1 of... 

Heparin has been used clinically for decades to prevent and treat thromboembolic disease and is isolated on an industrial scale from animal tissues, in particular pig intestinal mucosa. The conesponding physiological blood anticoagulant is presumably not heparin, but an HS species that is located on the surface of vascular endothelial cells. Both heparin and HS contain a specific pentasaccharide sequence that binds and activates the plasma proteinase inhibitor AT. This pentasaccharide sequence (4) is present only in a subfraction of heparin and HS preparations. It displays a characteristic structural feature, namely a 3-0-sulfated GlcN residue, that is only rarely seen in other portions of heparin/HS chains. 

Polysulfates of oxidized starches, being heparin-like compounds, show blood anticoagulant activity. Their activity increases with the number of sulfate residues, and the 6-carboxyl groups decreased the toxicity of the compound.533-536,619 Complexes of these anticoagulants with pepsin had no proteolytic activity.620,621 Methyl... 

The tests carried out for the evaluation of the blood anticoagulant activity of sulfated N-carboxymethyl chitosan are the same as those for the determination of heparin, i.e. the antithrombin test for the thrombin inhibition and the heparin test for the factor Xa inhibition. Both of these tests were done by spectrophotometry at 405 nm on the p-nitroaniline liberated from a chromo-genic substrate. 

Natural sulfate acid esters occur as salts in many seaweed polysaccharides (138). They are also found widely distributed in the polysaccharides (139) of animal tissues (Chapter XII), such as those in skin, cartilage, cornea, and gastric mucin. Heparin (p. 720) (140), the natural blood anticoagulant, is a highly sulfated polysaccharide of this type and contains both sulfate acid ester groups and a sulfamic acid function, RNHSO2OH. 

Carbohydrate sulfates are important in polysaccharide chemistry as several sulfated polysaccharides occur naturally in seaweeds, and human tissue contains heparin, the blood anticoagulating agent, a sulfated polysaccharide which also contains A -sulfate groups." Sulfation of polysaccharides by chlorosulfonic acid-pyridine leads to the incorporation of pyridinium substituents on a proportion of the reducing end groups. ... 

Heparin, a sulfated polysaccharide and a natural blood anticoagulant (Chapter 6, ref. 33) may be converted into the polysulfate, used in the treatment of retroviral diseases, by reaction of heparin pyridinum salt with chlorosulfonic acid in pyridine at 50 C. ... 

Chitin and chitosan derivatives have also been studied as blood compatible materials both in vivo and in vitro [520], Anticoagulant activity was greatest with O sulfated N acetyl chitosan, followed by N,0 sulfated chitosan, heparin, and finally sulfated N acetyl chitosan. The lipolytic activity was greatest for N,0 sulfated chitosan followed by heparin. The generally poor performance of chitosan was attributed to polyelectrolyte complexes with free amino groups present on the membrane surface. The O sulfate or acidic group at the 6 position in the hexosamine moiety was identified as the main active site for anticoagulant activity. 

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