Effect of i. v. and Oral Administration of Heparinoids G31150, G31150-A and of Nitrilotriacetic Acid on Blood Coagulation^[*]

Summary

The heparinoid G31150-A and nitrilotriacetic acid (NTA) were compared with heparinoid G31150 and heparin. In vitro the anticoagulant activity of NTA was 1/20000, G31150-A 1/8th and G31150, 1/10th of heparin. On intravenous injection in dogs, the degree and duration of hypocoagulability was about the same for the two heparinoids but less than predicted from the effects in vitro. Injection of 25 mg NTA/kg caused a slight increase in coagulation time lasting over 4 hours. When heparinoid G31150-A and NTA were given orally, there was an increase in clotting time of blood and metachromatic activity appeared in the urine. The greatest amount of activity was excreted with the highest dose of NTA alone. Microelectrophoresis of the urinary concentrate indicated the excreted material after NTA was not heparin, but another mucopolysaccharide; after G31150, a heparinoid. These results were confirmed by the resulting absorption spectrum of the dye obtained with added urinary concentrate. It is suggested that the effects produced when a chelating agent is given with oral heparin and heparinoids may be due to the release of a mucopolysaccharide.

^*) Data from a thesis presented to the University of Saskatchewan in p artial fulfilment of requirements for the degree of Doctor of Philosophy.

• References

• 1 Astrup P. On the determination of heparin in blood plasma and urine. Acta pharmacol. (Kbh) 03: 165 1947;
• 2 Geigy J, Company R. Basic Data on Preheparinoid G31150-A. June, 1963
• 3 Jaques L. B. 3. Preparation of Glassware. In The Coagulation of Blood - Methods of Study. Ed. Tocantins L. M. 7 Grune & Stratton; 1955
• 4 Jaques L. B, Ballieux R. E, Dietrich G. P, Kavanagh L. W. A microelectrophoresis method for heparin. Canad. J. Physiol. Pharmacol 46: 351 1968;
• 5 Jaques L. B, Bell H. J. The determination of heparin. In Methods of Biochemical Analysis. 7 253: Inter science Publishers Inc; New York: 1959
• 6 Jaques L. B, Kavanagh L. W, Lavallee A. A comparison of biological activities and chemical analysis for various preparations of heparin. Arzneimittel-Forsch 17: 114 1967;
• 7 Jaques L. B, Mustard R. A. Some factors affecting the anticoagulant action of heparin. Biochem. J 34: 153 1940;
• 8 Jaques L. B, NapTce E, Levy S. W. The metachromatic activity of urine following the injection of heparin. Circulat. Res 01: 321 1953;
• 9 Jaques L. B, Wollin A. The azure A colour reaction of heparin and its relation to metachromasia. Canad. J. Physiol. Pharmacol 45: 787 1967;
• 10 Jarrett G. L, Jaques L. B. The anticoagulant and metachromatic properties of the heparinoid G31150 in dogs. Canad. J. Physiol. Pharmacol 42: 93 1964;
• 11 Jarrett G. L, Jaques L. B. The antithrombosis activity of the heparinoid G31150. Thrombos. Diathes. haemorrh. (Stuttg) 10: 431 1964;
• 12 Schanker L. S, Johnson J. M. Increased intestinal absorption of foreign organic compounds in the presence of ethylene diaminetetra-acetic acid. Biochem. Pharmacol 08: 421 1961;
• 13 Windsor E, Gronheim G. E. Gastro-intestinal absorption of heparin and synthetic heparinoids. Nature 190: 263 1961;