Processes for immobilising biological entities

Abstract

According to the invention there is provided inter alia a process for the manufacture of a solid object having a surface comprising a layered coating of cationic and anionic polymer wherein the outer coating layer comprises an anticoagulant entity, comprising the steps of:i) treating a surface of the solid object with a cationic polymer;ii) treating the surface with an anionic polymer;iii) optionally repeating steps i) and ii) one or more times;iv) treating the surface with a cationic polymer; andv) treating the outermost layer of cationic polymer with an anticoagulant entity, thereby to covalently attach the anticoagulant entity to the outermost layer of cationic polymer; wherein, the anionic polymer is characterized by having (a) a total molecular weight of 650 kDa-10,000 kDa; and (b) a solution charge density of >4 μeq / g; and wherein, step ii) is carried out at a salt concentration of 0.25 M-5.0 M.

Description

FIELD OF THE INVENTION[0001]The present invention relates to processes for preparing solid objects having surface coatings comprising biological entities. In particular, the present invention relates to processes for preparing improved surface coatings comprising anticoagulant entities such as heparin and certain products obtained thereby.BACKGROUND OF THE INVENTION[0002]When a medical device is implanted in the body or is in contact with body fluids, a number of different reactions are set into motion, some of them resulting in inflammation and some in the coagulation of the blood in contact with the device surface. In order to counteract these serious adverse effects, the well-known anticoagulant compound heparin has for a long time been administered systemically to patients before the medical device is implanted into their body, or when it is in contact with their body fluids, in order to provide an antithrombotic effect.[0003]Thrombin is one of several coagulation factors, all o...

AI Technical Summary

Benefits of technology

This patent describes a process for coating solid objects with an anticoagulant entity, resulting in several technical benefits. The coating is uniform and smooth, and can mask the properties of the object, improving its resistance to thromboresFurthermore, the coating contains good anticoagulant activity, is thromboresistant, has a long lifetime, and is preserved upon sterilization. It can also have self-healing properties and reduce the need for systemic administration of anticoagulants. Additionally, it can have anti-inflammatory properties and can be used in analytical or separation devices with good binding capacity to biomolecules.

Problems solved by technology

When a medical device is implanted in the body or is in contact with body fluids, a number of different reactions are set into motion, some of them resulting in inflammation and some in the coagulation of the blood in contact with the device surface.

Systemic treatment with high doses of heparin is, however, often associated with serious side-effects of which bleeding is the predominant.

Another rare, but serious complication of heparin therapy is the development of an allergic response called heparin induced thrombocytopenia (HIT) that may lead to thrombosis (both venous and arterial).

Therefore, solutions have been sought where the need for a systemic heparinization of the patient would be unnecessary or can be limited.

Ionic binding of heparin to polycationic surfaces was thus attempted, but the surface modifications suffered from lack of stability resulting in lack of function, as the heparin leached from the surface.

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