Efficacy of Heparinoid PSS in Treating Cardiovascular Diseases and Beyond-A Review of 27 Years Clinical Experiences in China.

Propylene glycol alginate sodium sulfate (PSS) is the world's first oral heparinoid approved by Chinese Food and Drug Administration in 1987. Propylene glycol alginate sodium sulfate is produced by modifying partially hydrolyzed alginate, one of the most abundant marine polysaccharides isolated from brown algae, by epoxypropane esterification and by chemical sulfation. It is used for treating and preventing cardiovascular-related diseases. The low cost (US$1.29/100 tablets, ∼4 tablets/day), remarkable clinical effects, and convenient oral administration make PSS an ideal long-term prevention drug. Propylene glycol alginate sodium sulfate is available in most drug stores in China, and millions of patients take PSS routinely during the past 27 years. The 22 784 reported clinical cases as well as the structure, preparation, clinical efficacy, adverse reactions, pharmacokinetics, pharmacodynamics, and future perspectives of PSS based on the results of peer-reviewed publications will be discussed. This review should bring the knowledge of PSS gained in China to the world to stimulate in depth academic and clinical studies of PSS.

Large-scale synthesis of 6-deoxy-6-sulfonatomethyl glycosides and their application for novel synthesis of a heparinoid pentasaccharide trisulfonic acid of anticoagulant activity.

Multigram-scale syntheses of three 6-deoxy-6-sulfonatomethyl α-glucosides were accomplished via reactions of the corresponding primary triflate derivatives with the lithiated ethyl methanesulfonate. Chemoselective glycosylation reactions of different 6-C-sulfonatomethyl glucoside donors were studied. The sulfonic acid-containing building blocks were utilised in a novel [2+3] block synthesis of a trisulfonic acid isoster of the anticoagulant pentasaccharide idraparinux.

Semi-synthetic heparinoids.

New chemical-enzymatic technology based on the modification of the bacterial polysaccharide K5 from Escherichia coli leads to the synthesis of a number of heparin/heparan sulfate-like molecules with different biological activities. With this technology, two families of sulfated compounds were synthesized, which differ in their uronic acid content. The first group contains only glucuronic acid, whereas the second group contains about 50% iduronic acid following epimerization by immobilized recombinant C5 epimerase. This has led to the development of various anticoagulant and nonanticoagulant K5 derivatives endowed with different - and sometimes highly specific - antitumor, antiviral, and/or anti-inflammatory activities.

Synthesis and non-thrombogenicity of heparinoid polyurethaneureas.

Unsaturated polyurethaneureas were synthesized from 4,4'-diphenylmethane diisocyanate, 1,2-diaminopropane and polybutadiene containing hydroxyl groups at both ends of a chain. The polyurethaneureas were cast as a film and subsequently treated with N-chlorosulphonyl isocyanate to produce sulphamate and carboxylate groups on the film surface. The level of in vitro non-thrombogenicity increased with increasing degree of modification. The high blood compatibility is attributed to the low level of platelet stimulation and to heparinoid activity. It was observed that platelet stimulation depends on the surface structure of the original polyurethaneura, and that the heparinoid activity is related with the presence of sulphamate and carboxylate groups.

Synthesis of new heparinoids with high anticoagulant activity.

New heparinoids were synthesized by the chemical method starting from ring-opening polymerization of anhydro sugar derivatives. Sulfation of synthetic (1----6)-alpha-linked 3-amino-3-deoxy-D-glucopyranan and its copolymers gave dextran-type heparinoids having a sulfamide group on the C-3 carbon of the sugar unit. Heparinoids with different sulfamide contents indicated that the anticoagulant activity (35.3-41.3 units/mg) is independent of the sulfamide content, while an increase in sulfamide content lowered the toxicity. Sulfation of (1----5)-alpha-D-xylofuranan and -ribofuranan provided furanan-type heparinoids the anticoagulant activities of which were higher than those of the corresponding sulfated pyranan-type polysaccharides (1----4)-beta-D-xylopyranan and -ribopyranan. The highest activity (69.1 units/mg) was shown by sulfated (1----5)-alpha-D-xylofuranan. The dextran-type heparinoid having a sulfamide group showed a high anticoagulant activity also in vivo and high lipemia-clearing activity.