1. Field of the Invention
This invention relates to biomedical devices, and more particularly relates to a polyurethane of high stability to body fluids which are suitable for long term implants.
2. Background of the Invention
Extensive investigations have been undertaken over many years to find materials that will be biologically and chemically stable toward body fluids. This area of research has become increasingly important with the development of various objects and articles which can be in contact with blood or other body fluids, such as artificial organs, vascular grafts, probes, cannulas, catheters and the like. Biostability is particularly important for articles intended for long term contact with the body environment.
Synthetic plastics are preferred materials for such articles. Polyurethanes in particular possess an outstanding balance of physical and mechanical properties and superior blood compatibility compared to other polymers such as silicone rubber, polyethylene, polyvinyl chloride and perfluorinated polymers. As a result, they have come to the fore as the preferred polymeric biomaterials for fabrication of various medical device components. Some important device applications for polyurethanes include peripheral and central venous catheters, coatings for heart pacemaker leads and the Jarvik heart.
Polyurethanes are synthesized from three basic components, a polyisocyanate, a polyglycol and an extender, usually a low molecular weight diol, diamine, aminoalcohol or water. If the extender is a diol, the polyurethane consists entirely of urethane linkages. If the extender is water, aminoalcohol or a diamine, both urethane and urea linkages are present and the polyurethane is more accurately and conventionally termed a polyurethaneurea. In the present disclosure, polyurethanes and polyurethaneureas are generically referred to as polyurethanes.
Polyurethanes are known to develop microdomains conventionally termed hard segments and soft segments, and as a result are often referred to as segmented polyurethanes. The hard segments form by localization of the portions of the polymer molecules which include the isocyanate and extender components and are generally of high crystallinity. The soft segments form from the polyglycol portions of the polymer chains and generally are either noncrystalline or of low crystallinity. Crystallinity and hard segment content are important contributing factors to polymer properties. A discussion of the effect of structure on the stability of polyurethanes has been presented by Lemm in Polyurethanes in Biomedical Engineering, H. Planck et al., ed., Elsevier Science Publishers, Amsterdam, The Netherlands, 1984, p 103.
The usual polyglycols for polyurethane synthesis are polyetherglycols and polyester lycols. It is, however, well-known that both of these classes of polyglycol soft segment components are subject to degradation in the body environment and may not be suitable for biomedical applications. On one hand, segmented polyurethanes produced from polyester diol soft segments may be subject to rapid hydrolysis of the ester functional group. On the other hand, polyurethanes produced with polyether diol soft segment have been reported to undergo extensive oxidative degradation. It is therefore desirable to eliminate these functional groups during the initial design of a potentially biostable polyurethane, and various disclosures have been directed to polyurethanes having other soft segments. Thus, Coury et al., in U.S. Pat. No. 4,873,308 discloses polyurethanes in which the soft segment is a hydrocarbon diol. Likewise, Murai et al., in U.S. Pat. No. 4,978,691 discloses polyurethanes in which the soft segment is a polycarbonate diol.
A second problem with respect to use of polymers for biomedical devices is the thrombogenic potential of polymeric surfaces in contact with blood. Thrombogenicity has conventionally been counteracted by the use of anticoagulents such as heparin. Various procedures for attachment of heparin to otherwise thrombogenic surfaces have been disclosed. Eriksson et al., in U.S. Pat. No. 3,634,123 discloses steeping a plastic surface sequentially in a solution of a cationic surface active agent and an aqueous solution of heparin to ionically bond the heparin. Improvements in the surface active agent method have been disclosed by Eriksson in U.S. Pat. No. 3,810,781, by Williams et al. in U.S. Pat. Nos. 4,349,467 and 4,613,517 and by Hu et al. in U.S. Pat. No. 4,865,870.
Ferruti et al. disclose the heparin binding capacity of crosslinked polyamidoamines prepared by reacting diamines with bis acryloylpiperazines (Biomaterials, 218 (1983). Azzuoli et al., in Biomaterials 8,61 (1987) coats a polyurethane with a diisocyanate, and reacts the diisocyanate with the polyamidoamine of Ferruti et al. supra. The grafted polyamidoamine is then protonated and treated with a heparin salt.
Covalent bonding of aldehyde-actuated heparin to an amine rich polyurethane surface is disclosed by Solomon et al. in U.S. Pat. No. 4,521,564.
While the above disclosures have improved materials for biomedical devices, further improvements, in particular long term stability are needed. The present invention is directed to fulfilling this need.