Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – From reactant having at least one -n=c=x group as well as...
Patent
1986-08-07
1987-08-25
Welsh, Maurice J.
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
From reactant having at least one -n=c=x group as well as...
2643281, 2643286, 2643288, 4273855, C08G 1838
Patent
active
046893865
DESCRIPTION:
BRIEF SUMMARY
This invention relates to biocompatible particularly haemocompatible surfaces and to new polymers based on phosphatidylcholine. Blood contacting prostheses are of major importance today in cardiovascular surgery and other fields of medicine. Heart valves and blood vessel prostheses, balloon pumps and catheters are being implanted in daily surgical practice to restore or diagnose cardiovascular function.
Artificial organs are routinely employed in blood detoxification by absorptive haemoperfusion and in oxygenation (membrane oxygenators and heart-lung devices). Considerable effort and capital is invested in Europe and the U.S.A. in the development and experimental evolution of an implantable artificial heart system. The devices are generally constructed from polymeric materials and when in use, a blood-polymer contact is present. This contact can cause a reaction in the recirculating blood, which, depending on the choice of material, the design parameter, the flow or the addition of the anticoagulants, may lead to protein deposition, adhesion and destruction of red blood cells (haemolysis), platelet (thrombocyte) adhesion and aggregation and blood coagulation leading to the formation of a haemostatic plug (thrombus). The occurrence of thromboembolism in cardiovascular surgery continues to be a problem, notwithstanding routine treatment with anticoagulants. For these reasons the search for biocompatible non-thrombogenic materials has been an important research objective over the last two decades. Our approach to this problem is to mimic the surface characteristics of cell membranes.
Biological membranes are important in all areas of the body. Every cell has an outer membrane and within the cell there are membranes that act to compartmentalise the various organelles, e.g. the mitochondria, nucleus and endoplasmic reticulum. Membranes are particularly important features of the functions of blood cells, e.g. erthrocytes and leucocytes. The various cell membranes, including those of red blood cells, are all built upon an asymmetric lipid matrix of polar lipids in which the intrinsic proteins are distributed. the outer surface of the lipid matrix of cells contains the grouping: ##STR1##
The outer polar surface is a common feature of red cells, platelets, lymphocytes, etc. The inner surface is different and usually contains the negatively charged lipids. Studies of cell systems have shown that the lipids which occur on the inner cell surface are pro-coagulant whilst those on the outer surface are thromboresistant (Zwaal, R. F. A. Comfurius, P. and van Deenen, L. M. M., Membrane asymmetry and blood coagulation, Nature, 1977, 268, 358-360).
The present invention provides a series of new polymers based upon reactions of polyols partially esterified by phosphatidylcholine or homologues thereof, isocyanates and optionally various diols or polyols, the latter having the effect of modulating the rheological characteristics of the resulting polymer. These new polymers mimic the thromboresistant surfaces of blood cell membranes and also have low antigenic character. The polymers of the invention range in rheological characteristics from soft to hard polymers and have useful applications to a variety of situations where biocompatibility particularly haemocompatibility are required ranging from new soft contact lens materials to polymers suitable for heart valves and other prosthetic devices.
The present invention provides a polyurethane reaction product of an aliphatic or aromatic di- or polyisocyanate and a diol or polyol having at least two hydroxyl groups capable of reacting with an isocyanate group and having the residue of at least one further hydroxyl group present in the form of a phosphorus acid ester of formula I: ##STR2## wherein n is 0 or 1, m is 2, 3 or 4 and each R independently is an alkyl group containing 1 to 4 carbon atoms.
The polymers of the present invention comprise essentially a polymer backbone having a polyurethane structure carrying pendant groups containing the phosphatidylcholine residue or homolo
REFERENCES:
patent: 3268360 (1966-08-01), Beninate et al.
patent: 3498969 (1970-03-01), Lewis
Chapman Dennis
Valencia Gregorio P.
Biocompatibles Ltd.
Welsh Maurice J.
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