摘要:
It has now been discovered that various mutant forms of pro-urokinase ('pro-UK') perform in the manner of pro-UK in lysing 'bad' blood clots (those clots that occlude blood vessels), while sparing hemostatic fibrin in the so-called 'good' blood clots (those clots that seal wounds, e.g., after surgery or other tissue injury). Thus, these pro-UK mutants are excellent and safe thrombolytic agents. These advantages allow them to be used in a variety of new methods, devices, and compositions useful for thrombolysis and treating various cardiovascular disorders in clinical situations where administration of other known thrombolytic agents has been too risky or even contraindicated. New methods of making the pro-UK mutants are also disclosed.
摘要:
A multi-step method of forming a coating on a substrate, such as a stent or graft, is disclosed. The steps of the method include treating the surface with a plasma formed at or near atmospheric pressure to form one or more active species on the surface until a desired surface density of the active species is formed, and exposing the treated surface to a selected gas or liquid under conditions effective to convert the active species to a stable functional group. The exposed surface surface may be contacted with a surface-modifying group under conditions effective to covalently attach the surface-modifying group to the functional group. Also disclosed is a substrate having a bioactive/biocompatible coating and/or a drug-releasable coating prepared by the method.
摘要:
The invention provides a method of causing the degradation of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances) by means of a fibrinolytic matrix metalloproteinase, preferably an MT1-MMP. The method of the invention can be performed in vitro to provide diagnostic information characterizing fibrin(ogen) and fibrinolytic physiology. The method can also be performed in vivo as a method of thrombolytic therapy in which a fibrinolytic matrix metalloproteinase is administered to a subject to degrade thrombus in situ. The fibrinolytic matrix metalloproteinase can be administered in conjunction with other active agents, preferably with agents having thrombolytic activity to improve thrombolytic and fibrinolytic therapy. The invention further provides compositions containing a fibrinolytic matrix metalloproteinase for the performance of fibrinolytic or thrombolytic procedures. Also provided are kits that include a fibrinolytic matrix metalloproteinase for performing fibrinolytic or thrombolytic procedures.
摘要:
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 a biomolecule such as 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 the biomolecule, such as 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.
摘要:
A medical device has a biocompatible coating made by reacting a reactive polysiloxane, an acetoxysilane crosslinking agent, a reinforcing silica and a metal catalyst. Such devices cause decreased reactions when they come into contact with a human or animal body or its blood, fluids or other biological membranes.
摘要:
Disclosed are implantable medical devices with enhanced patency. Expanded polytetrafluoroethylene small caliber vascular grafts coated with polymer bound bio-active agents that exhibit enhanced patency are disclosed. Methods of preparing same are also provided.
摘要:
A method for making a medical device having a biomolecule immobilized on a substrate surface is provided. The method comprises the steps of: (a) oxidizing 2-aminoalcohol moieties with a periodate to form an aldehyde-functional material; (b) combining the aldehyde-functional material with an amino-functional material to bond the two materials together through an imine moiety; and (c) reacting the imine moiety with a reducing agent to form a secondary amine.
摘要:
The present invention is directed to thrombo-resistant coatings for use with gas permeable biomedical devices and implants. The coatings include a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A quantity of at least one bioactive molecule designed to counteract a specific blood-material incompatibility reaction is covalently bonded to the poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain. The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is preferably achieved by plasma etching with ammonia gas. The amine-containing siloxane surface is reacted with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine groups on the siloxane surface. The material is then reacted with a solution of at least one bioactive molecule which counteracts a blood-material incompatibility reaction, such that a single bioactive molecule is coupled to a single poly(ethylene oxide) chain. The resulting siloxane surface is capable of resisting blood-material incompatibility reactions while maintaining high gas permeability.