Luhan Pharmachem Co., Ltd.

Luhan pharmachem Co., Ltd. supplies Heparin Sodium bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Heparin Sodium is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.

What is Heparin Sodium?

Heparin, a highly sulfated glycosaminoglycan, is widely used as an injectableanticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and renal dialysismachines. Although it is used principally in medicine for anticoagulation, its true physiological role in the body remains unclear, because blood anticoagulation is achieved mostly by heparan sulfate proteoglycans derived from endothelial cells. Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials. In addition, it is observed across a number of widely different species, including some invertebrates that do not have a similar blood coagulation system.

In nature, heparin is a polymer of varying chain size. Unfractionated heparin as a pharmaceutical is heparin that has not been fractionated to sequester the fraction of molecules with low molecular weight. In contrast, low-molecular-weight heparin has undergone fractionation for the purpose of making its pharmacodynamics more predictable. Heparin is on the World Health Organization’s List of Essential Medicines, a list of the most important medications needed in a basic health system.

What is the usage of Heparin Sodium?

Heparin is a naturally occurring anticoagulant produced by basophils and mast cells. Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed (unlike tissue plasminogen activator), it allows the body’s natural clot lysis mechanisms to work normally to break down clots that have formed. Heparin is generally used for anticoagulation for the following conditions:

• Acute coronary syndrome, e.g., NSTEMI
• Atrial fibrillation
• Deep-vein thrombosis and pulmonary embolism
• Cardiopulmonary bypass for heart surgery
• ECMO circuit for extracorporeal life support
• Hemofiltration
• Indwelling central or peripheral venous catheters

What’s the mechanism of action?

Heparin and its low-molecular-weight derivatives (e.g., enoxaparin, dalteparin, tinzaparin) are effective at preventing deep vein thromboses and pulmonary emboli in patients at risk, but no evidence indicates any one is more effective than the other in preventing mortality. Heparin binds to the enzyme inhibitor antithrombinIII (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivatesthrombin and other proteases involved in blood clotting, most notably factor Xa. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin. AT binds to a specific pentasaccharide sulfation sequence contained within the heparin polymer: GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S)

The conformational change in AT on heparin-binding mediates its inhibition of factor Xa. For thrombin inhibition, however, thrombin must also bind to the heparin polymer at a site proximal to the pentasaccharide. The highly negative charge density of heparin contributes to its very strong electrostatic interaction with thrombin. The formation of a ternary complex between AT, thrombin, and heparin results in the inactivation of thrombin. For this reason, heparin’s activity against thrombin is size-dependent, with the ternary complex requiring at least 18 saccharide units for efficient formation. In contrast, antifactor Xa activity requires only the pentasaccharide binding site.

This size difference has led to the development of low-molecular-weight heparins(LMWHs) and, more recently, to fondaparinux as pharmaceutical anticoagulants. LMWHs and fondaparinux target antifactor Xa activity rather than antithrombin activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic index. The chemical structure of fondaparinux is shown above. It is a synthetic pentasaccharide, whose chemical structure is almost identical to the AT binding pentasaccharide sequence that can be found within polymeric heparin and heparan sulfate.

With LMWH and fondaparinux, the risk of osteoporosis and heparin-induced thrombocytopenia (HIT) is reduced. Monitoring of the activated partial thromboplastin time is also not required and does not reflect the anticoagulant effect, as APTT is insensitive to alterations in factor Xa.

Danaparoid, a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate can be used as an anticoagulant in patients having developed HIT. Because danaparoid does not contain heparin or heparin fragments, cross-reactivity of danaparoid with heparin-induced antibodies is reported as less than 10%.

The effects of heparin are measured in the lab by the partial thromboplastin time (aPTT), one of the measures of the time it takes the blood plasma to clot. Partial thromboplastin time should not be confused with prothrombin time, or PT, which measures blood clotting time through a different pathway of the coagulation cascade.
Heparin enhances ATIII activity and neutralizes “activated serine protease coagulation factors.”

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.