Implantable medical device

Details Implantable medical device Implantable medical device

1999-10-04

2001-08-07

Page, Thurman K. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Implant or insert

C424S423000

Reexamination Certificate

active

06270788

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a method for making a biocompatible medical article, and preferably, a blood compatible medical article. In particular, this invention relates to a method of making blood compatible medical articles through the use of an alcohol-based polymer carrier suitable for the subsequent attachment of a bioactive molecule, such as heparin.
BACKGROUND OF THE INVENTION
The development of medical articles that contact physiological fluids, particularly blood, is a rapidly developing area of medicine. This has been hampered, however, by the lack of suitable synthetic materials that are stable when contacted with such fluids.
Adverse reactions between materials and blood components are predominant factors limiting the use of synthetic materials that come into contact with physiological fluids. For example, catheters, vascular grafts, and the like, tend to serve as a nidus, or focus, for the formation of thrombi (blood clots). Initial contact of such materials with blood results in deposition of plasma proteins, such as albumin, fibrinogen, immunoglobulin, coagulation factors, and complement components. The adsorption of fibrinogen onto the surface of the material causes platelet adhesion, activation, and aggregation. Other cell adhesive proteins, such as fibronectin, vitronectin, and von Willebrand factor (vWF) also promote platelet adhesion. As a result, the continual use of anticoagulants in conjunction with the introduction of such materials to the body is often necessary.
Furthermore, complement activation occurs when materials are introduced into blood. Adsorption of large amounts of IgG, IgM, and C3b onto surfaces causes activation. Subsequently, complexes may be formed which contribute to undesirable immune responses, such as proteolysis, cell lysis, opsonization, anaphylaxis, and chemotaxis. As a result, these responses render such materials incompatible with the living body.
A number of approaches have been suggested to improve the biocompatibility, and even blood compatibility, of medical articles. One approach which has met with some success is to couple anticoagulants to the surface of biologically inert materials to impart antithrombogenic characteristics to the materials. Among the anticoagulants bound to the surface is heparin. It has been found generally that heparinized surfaces greatly reduce the generation of thrombus and thus cellular activation of blood contacting them, because heparin is a potent inhibitor of thrombin generation.
Although many different methods have been disclosed for heparinizing a surface, the problem still exists to combine in one method the following features: (I) technological simplicity and wide applicability in terms of the substrate materials; (II) stability/durability of coating, (III) high bioactivity of attached heparin. (I) The most simple and universal method of surface modification of a medical article is a dip coating (or pumping through) the device in a solution of the proper polymer, followed by the solvent evaporation. Since the organic solution should be preferably used for the good wetting and coating of plastics, the haemocompatible polymer must be soluble in a non-toxic, chemically not aggressive organic solvent, such as, for example, ethanol. (II) Such a polymer, however, has to be insoluble in water, because the coating should be stable upon the contact with blood. (III) The polymer must include heparin in its structure or must have the functional chemical group, which is required for subsequent heparin coupling. Preferably, the polymer must be a copolymer, having both hydrophobic and hydrophilic segments. The hydrophobic segments are required to anchor the polymer to the substrate surface, while hydrophilic segments must provide an extra mobility to heparin molecule, which is important to achieve a high biological activity of heparin.
It is thus an object of the present invention to provide a method of producing a haemocompatible coating from a polymer or copolymer as the primary layer which is soluble in a non-toxic, chemically not aggressive organic solvent, such as, for example, ethanol.
It is a further object of the present invention to provide a method of producing such a polymer or copolymer which is also insoluble in water and will thus be stable upon the contact with blood.
It is a further object of the present invention to provide a method of producing such a polymer or copolymer which has a functional chemical group, which is required for subsequent heparin coupling.
It is a further object of the present invention to provide a method of producing such a polymer or copolymer which has both hydrophobic and hydrophilic segments.
SUMMARY OF THE INVENTION
The present invention meets these and other objects by providing a method for making a biocompatible medical article, and preferably, a blood compatible medical article, through the use of a copolymer coating. The copolymer coating is synthesized using methacrylate or acrylate monomers with a functional group (primary amino group) for subsequent attachment of heparin. Synthesis of the copolymer coating is carried out using the proper proportion of hydrophobic monomer/hydrophilic monomer/functional monomer in order to optimize the solubility of the copolymer in alcohol, its insolubility in water (before and after heparin coupling), the heparin coupling efficacy and heparin bioactivity. Once the copolymer coating is fashioned, a medical article is coated with it. The coating is thereafter dried and heparin attached. In such a manner the present invention provides for a method for making a biocompatible medical article, and preferably, a blood compatible medical article.


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patent: 5755758 (1998-05-01), Woloszko et al.
patent: 5866113 (1999-02-01), Hendriks et al.
patent: 4 07238124 (1994-03-01), None

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