Multicomponent complex for use with a substrate

Abstract

Compositions and methods for use with substrates which are useful in the sustained delivery of bioeffecting agents are described. The compositions of the invention include a multicomponent complex which attaches a bioeffecting agent to a substrate with an anchor provided by a linker compound which also forms a cleavable linkage so that the bioeffecting agent's release into the area surrounding the substrate occurs in a sustained manner over an extended period of time. The methods of the invention involve providing a bioeffecting composition on the surface of a substrate so that a bioeffecting agent may be released in a sustained manner over time.

What is claimed is:  
     
         1 . The combination of a multicomponent complex for delivering a bioeffecting agent for use with a substrate and an article, comprising a first complex for use with a substrate and for delivering a bioeffecting agent having the following formula:  
       [Q]-[S]-[T] wherein Q is a bioeffecting domain component;    S is a segment component containing at least two linking domains; and    T is an anchoring moiety component,    the components selected such that a cleavable linkage anchored to the substrate is formed which sustains the release of the bioeffecting agent over time, and a second article in contact with the first complex.    
     
     
         2 . The combination of  claim 1  wherein the bioeffecting domain component is supplied by a compound which has a property selected from the group consisting of agents with antithrombogenic, antimicrobial, antiinflammatory, analgesic, and cell growth properties.  
     
     
         3 . The combination of  claim 2  wherein the agent is a heparin compound.  
     
     
         4 . The combination of  claim 3  wherein the heparin compound is ammonium heparin.  
     
     
         5 . The combination of  claim 1  wherein the bioeffecting domain component is supplied by a compound selected from the group consisting of vitamins, mineral complexes, proteins and enzymes.  
     
     
         6 . The combination of  claim 5  wherein the bioeffecting domain component is supplied by a compound which is a cell growth factor.  
     
     
         7 . The combination of  claim 1  wherein the cleavable linkage is an ester.  
     
     
         8 . The combination of  claim 1  wherein the segment component is supplied by a compound selected from the group consisting of aziridines, epoxys, formaldehydes and metal esters.  
     
     
         9 . The combination of  claim 8  wherein the segment component is supplied by an aziridine.  
     
     
         10 . The combination of  claim 1  wherein the article is a medical device.  
     
     
         11 . The combination of  claim 10  wherein the medical device is adapted for in vivo uses.  
     
     
         12 . A multicomponent complex for delivering a bioeffecting agent for use with a substrate having the following formula:  
       [Q]-[S]-[T] wherein Q is a bioeffecting domain component;    S is a segment component containing at least two linking domains; and    T is an anchoring moiety component,    the components selected such that a cleavable linkage anchored to the substrate is formed which sustains the release of the bioeffecting agent over time.    
     
     
         13 . The complex of  claim 12  wherein the bioeffecting domain component is supplied by a compound with a property selected from the group consisting of agents with antithrombogenic, antimicrobial, antiinflammatory, analgesic, and cell growth properties.  
     
     
         14 . The complex of  claim 13  wherein the agent is a heparin compound.  
     
     
         15 . The complex of  claim 14  wherein the heparin compound is ammonium heparin.  
     
     
         16 . The complex of  claim 12  wherein the bioeffecting domain component is supplied by a compound selected from the group consisting of vitamins, mineral complexes, proteins and enzymes.  
     
     
         17 . The complex of  claim 16  wherein the bioeffecting domain component is supplied by a growth factor.  
     
     
         18 . The complex of  claim 12  wherein the cleavable linkage is an ester.  
     
     
         19 . The complex of  claim 12  wherein the segment component is supplied by a compound selected from the group consisting of aziridines, epoxys, formaldehydes and metal esters.  
     
     
         20 . The complex of  claim 19  wherein the segment component is supplied by an aziridine.  
     
     
         21 . The complex of  claim 12  wherein the anchoring moiety component is supplied by a urethane.  
     
     
         22 . The complex of  claim 12  wherein the substrate is a medical device.  
     
     
         23 . The complex of  claim 22  wherein the medical device is adapted for in vivo uses.  
     
     
         24 . A composition for delivering a bioeffecting agent for use with a substrate comprising: 
 a first complex for use with a substrate and for delivering a bioeffecting agent having the following formula:    [Q]-[S]-[T]   wherein Q is a bioeffecting domain component;    S is a segment component containing at least two linking domains; and    T is an anchoring moiety component,    the components selected such that a cleavable linkage anchored to the substrate is formed which sustains the release of the bioeffecting agent over time, and    a second solution in contact with the first complex.    
     
     
         25 . The composition of  claim 24  wherein the compounds supplying Q, S and T are provided in a container as a single component.  
     
     
         26 . The composition of  claim 24  wherein the compounds supplying Q, S and T are provided as two components.  
     
     
         27 . The composition of  claim 24  wherein the compounds supplying Q, S and T are provided as three components.  
     
     
         28 . The composition of any of claims  25 ,  26  or  27  wherein Q is supplied by a compound with a property selected from the group consisting of pharmaceuticals with antithrombogenic, antimicrobial, antiinflammatory, analgesic, and cell growth properties.  
     
     
         29 . The composition of  claim 28  wherein the pharmaceutical is a heparin compound.  
     
     
         30 . The composition of  claim 29  wherein the heparin compound is ammonium heparin.  
     
     
         31 . The composition of any of claims  25 ,  26  or  27  wherein Q is supplied by a compound selected from the group consisting of vitamins, mineral complexes, proteins and enzymes.  
     
     
         32 . The composition of  claim 31  wherein Q is supplied by a growth factor.  
     
     
         33 . The composition of any of claims  25 ,  26  or  27  further comprising a hydrophilic agent.  
     
     
         34 . The composition of any of claims  25 ,  26  or  27  wherein the cleavable linkage is an ester.  
     
     
         35 . The composition of any of claims  25 ,  26  or  27  wherein S is supplied by a compound selected from the group consisting of aziridines, epoxys, formaldehydes and metal esters.  
     
     
         36 . The composition of  claim 35  wherein S is supplied by an aziridine.  
     
     
         37 . The composition of any of claims  25 ,  26  or  27  wherein the anchoring moiety component is supplied by a urethane.  
     
     
         38 . The complex of any of claims  25 ,  26  or  27  wherein the substrate is a medical device.  
     
     
         39 . The complex of  claim 38  wherein the medical device is adapted for in vivo uses.  
     
     
         40 . A packaged composition for delivering a bioeffecting agent for use with a substrate comprising: 
 a container holding a compound supplying at least one component of a multicomponent complex having the following formula:    [Q]-[S]-[T]   wherein Q is a bioeffecting domain component;    S is a segment component containing at least two linking domains; and    T is an anchoring moiety component,    the components selected such that a cleavable linkage anchored to the substrate is formed which sustains the release of the bioeffecting agent over time, and instructions for using the composition for delivering a bioeffecting agent.    
     
     
         41 . The packaged composition of  claim 40  wherein the compound supplying Q is contained in the package.  
     
     
         42 . The packaged composition of  claim 40  wherein the compound supplying S is contained in the package.  
     
     
         43 . The packaged composition of  claim 40  wherein the compound supplying T is contained in the package.  
     
     
         44 . The packaged composition of  claim 40  wherein the bioeffecting domain component is supplied by a compound with a property selected from the group consisting of agents with antithrombogenic, antimicrobial, antiinflammatory, analgesic, and cell growth properties.  
     
     
         45 . The packaged composition of  claim 44  wherein the agent is a heparin compound.  
     
     
         46 . The packaged composition of  claim 45  wherein the heparin compound is ammonium heparin.  
     
     
         47 . The packaged composition of  claim 40  wherein the bioeffecting domain component is supplied by a compound selected from the group consisting of vitamins, mineral complexes, proteins and enzymes.  
     
     
         48 . The packaged composition of  claim 40  wherein the bioeffecting domain component is supplied by a growth factor.  
     
     
         49 . The packaged composition of  claim 40  wherein the cleavable linkage is an ester.  
     
     
         50 . The packaged composition of  claim 40  wherein the segment component is supplied by a compound selected from the group consisting of aziridines, epoxys, formaldehydes and metal esters.  
     
     
         51 . The packaged composition of  claim 40  wherein the segment component is supplied by an aziridine.  
     
     
         52 . The packaged composition of  claim 40  wherein the anchoring moiety component is supplied by a urethane.  
     
     
         53 . The packaged composition of  claim 40  wherein the substrate is a medical device.  
     
     
         54 . The packaged composition of  claim 53  wherein the medical device is adapted for in vivo uses.  
     
     
         55 . A method for providing a sustained release bioeffecting coating on the surface of an article, the method comprising: 
 applying a coating solution to a surface of the article such that a layer containing the sustained release bioeffecting coating is formed upon the article surface, wherein the formed layer contains a multicomponent complex containing a bioeffecting domain component, a segment component containing at least two linking domains, and an anchoring moiety component, the components selected such that a cleavable linkage anchored to the substrate is formed, and the release of the bioeffecting domain is sustained over time.    
     
     
         56 . The method of  claim 55  wherein the bioeffecting domain component is supplied by a compound with a property selected from the group consisting of agents with antithrombogenic, antimicrobial, antiinflammatory, analgesic, and cell growth properties.  
     
     
         57 . The method of  claim 56  wherein the agent is a heparin compound.  
     
     
         58 . The method of  claim 57  wherein the heparin compound is ammonium heparin.  
     
     
         59 . The method of  claim 55  wherein the bioeffecting domain component is supplied by a compound selected from the group consisting of vitamins, mineral complexes, proteins and enzymes.  
     
     
         60 . The method of  claim 59  wherein the bioeffecting domain component is supplied by a growth factor.  
     
     
         61 . The method of  claim 55  wherein the coating solution contains a hydrophilic agent.  
     
     
         62 . The method of  claim 55  wherein the cleavable linkage is an ester.  
     
     
         63 . The method of  claim 55  wherein the segment component is supplied by a compound selected from the group consisting of aziridines, epoxys, formaldehydes and metal esters.  
     
     
         64 . The method of  claim 63  wherein the segment component is supplied by an aziridine.  
     
     
         65 . The method of  claim 55  wherein the article is a medical device.  
     
     
         66 . The method of  claim 55  wherein the medical device is adapted for in vivo uses.