geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Efficacy of orally active chemical conjugate of low molecular weight heparin and deoxycholic acid in rats, mice and monkeys


, : Efficacy of orally active chemical conjugate of low molecular weight heparin and deoxycholic acid in rats, mice and monkeys. Journal of Controlled Release 111(3): 290-298

Deoxycholic acid (DOCA) is a bile acid that facilitates the gastrointestinal (GI) absorption of low molecular weight heparin (LMWH) by bonding chemically to it. The calculated coupling ratio and bioactivity of LMWH-DOCA was 3.6 and 126.8 IU/mg, respectively. This study examined the efficacy of orally administered LMWH-DOCA in rat, mouse and monkey models. When 100 mg/kg (12,680 IU/kg) of LMWH-DOCA was administered to rats or mice, its maximum anti-factor Xa activity was 0.76 +/- 0.15 and 0.15 +/- 0.03 IU/ml, respectively. On the other hand, when a single dose of 100mg/kg LMWH-DOCA mixed with either a bile solution or 200 mg/kg free DOCA was administered to mice, the antifactor Xa activity of LMWH-DOCA was 0.42-0.45 IU/ml. Fluorescence studies confirmed that the free bile acid induced the morphological change in LMWH-DOCA in the buffer solution. In the monkey experiments, the bioavailability of LMWH-DOCA after administering 200 mg/kg free DOCA orally was 6.8%, which was 8 times higher than that of LMWH (0.8%) and 4 times higher than that of LMWH-DOCA in the absence of free DOCA (1.7%). The absorption of orally administered LMWH-DOCA occurred in all parts of the small intestine, particularly in the ileum without causing any damage such as fusion of the microvilli and dissolution or disorientation of the cell layers. The optimum oral formulation for LMWH-DOCA delivery in each animal model was determined according to the different absorption behavior of LMWH-DOCA. (c) 2006 Elsevier B.V. All rights reserved.

US$19.90

PMID: 16497407

DOI: 10.1016/j.jconrel.2005.12.011


Other references

de Andrade Ramos, B.Ribeiro.; Witkin, S.S., 2016: The influence of oxidative stress and autophagy cross regulation on pregnancy outcome. The generation of reactive oxygen species (ROS), a byproduct of aerobic energy metabolism, is maintained at physiological levels by the activity of antioxidant components. Insufficiently opposed ROS results in oxidative stress characterized by alt...

Barry, V.B.; Raiff, B.R., 2013: Weight management preferences in a non-treatment seeking sample. Obesity is a serious public health issue in the United States, with the CDC reporting that most adult Americans are now either overweight or obese. Little is known about the comparative acceptability of available weight management approaches in no...

Vlachos P.; Poulos L.; Koutselinis A.; Papadatos K., 1978: Euphorbia poisoning case reports. IRCS (International Research Communications System) Medical Science Library Compendium 6(3): 104

Serantes, Maria E., 1943: Accion de los anestesicos en la composition mineral del cerebro. Rats anesthetized with salts of Mg, CHCl3, or chloral hydrate have more than the normal amt. of K in the brain. Urethane anesthesia does not affect the level of K and ether anesthesia causes a diminution. Mg is more abundant in the brains of rats...

Grutter, Alexandra S., 1995: Relationships between cleaning rates and ectoparasite loads in coral reef fishes. Individuals from 11 fish species were followed and the number of times and duration that fish were inspected by the cleaner wrasse Labroides dimidiatus were recorded around Lizard Island, Great Barrier Reef. The frequency and duration of inspectio...

Fernandez Madrid, F., 1993: 1992 Pinot noir yeast trials. American Journal of Enology & Viticulture 44(4): 477

Kendall, A.I., 1911: The Biology and Biochemistry of Bacteria and their Relation to Therapeutics. Journal of Medical Research 24(2): 411-424

Dolynna, O.V., 2015: Neurohumoral effect of the dopaminergic system on development of alimentary-constitutional obesity. Decrease in quantity and activity of dopamine receptors at patients with obesity is established. This leads to overeating, and abnormal weight gain. The article presents data on the impact of the dopaminergic system in the levels of leptin, prolac...

Richard, A., 1966: Action de la temperature sur levolution genitale de Sepia officinalis L. Cr hebd Seanc Acad Sci Paris, 263D 1998-2001

Tresch, M.C.; Cheung, V.C.K.; d'Avella, A., 2006: Matrix factorization algorithms for the identification of muscle synergies: evaluation on simulated and experimental data sets. Several recent studies have used matrix factorization algorithms to assess the hypothesis that behaviors might be produced through the combination of a small number of muscle synergies. Although generally agreeing in their basic conclusions, these...