Apparatus and methods for controlled substance delivery from implanted prostheses

Abstract

The present invention provides improved stents and other prostheses for delivering substances to vascular and other luminal and intracorporeal environments. In particular, the present invention provides luminal prostheses which allow for a programmed and controlled substance delivery protocols for a variety of purposes. The prostheses comprise a scaffold which is implantable within a body lumen and a substance reservoir present over at least a portion of the scaffold. Usually, a rate-controlling element will be formed over the substance-containing reservoir to provide for a number of different substance release characteristics.

1 . A device for intracorporeal use within a patient's body, comprising: 
 an implantable scaffold;    at least one source of at least one therapeutic capable agent associated with the scaffold and configured to release the therapeutic capable agent within the patient's body at a controlled rate; and    a rate-controlling element layer covering at least a portion of the source and including at least one therapeutic capable agent and providing for an initial relatively more rapid release of the at least one therapeutic capable agent therapeutic from the rate-controlling element layer as well as a sustained, controlled release of the at least one therapeutic capable agent from the source.    
     
     
         2 . A device for intracorporeal use within a patient's body, comprising: 
 an implantable scaffold;    at least one source of at least one therapeutic capable agent associated with the scaffold; and    a rate-controlling element disposed adjacent at least a portion of the source and being configured to control the release of the therapeutic capable agent in the patient's body at an initial rate and at a subsequent rate relatively slower than the initial rate.    
     
     
         3 . A device as in  claim 1  or  2  wherein the rate-controlling element covers only a portion of the source.  
     
     
         4 . A device as in  claim 1  or  2  wherein the source comprises a reservoir.  
     
     
         5 . A device as in  claim 4  wherein the reservoir is at least partially disposed over the expandable structure.  
     
     
         6 . A device as in  claim 5  wherein the reservoir is disposed adjacent the luminal facing surface.  
     
     
         7 . A device as in  claim 5  wherein the reservoir is disposed adjacent the tissue facing surface.  
     
     
         8 . A device for intracorporeal use within a patient's body, comprising: 
 a radially expansible implantable scaffold having a plurality of regions exhibiting different mechanical profiles during the expansion of the scaffold and including relatively lower and relatively higher mechanical profiles; and    a source of at least one therapeutic capable agent comprising a plurality of segments and disposed adjacent at least a portion of the scaffold.    
     
     
         9 . A device as in  claim 8  wherein the segments are disposed adjacent the relatively lower mechanical profile regions.  
     
     
         10 . A device as in  claim 8  wherein the segments are disposed adjacent the relatively higher mechanical profile regions.  
     
     
         11 . A device as in  claim 8  wherein the segments are disposed adjacent only the regions that do not undergo substantial bending, flexing, stretching, or compressing upon the expansion of the scaffold.  
     
     
         12 . A device as in  claim 8  wherein the segments are disposed adjacent only the regions that do not undergo more than about 5% of bending, flexing, stretching, or compressing upon the expansion of the scaffold.  
     
     
         13 . A device as in  claim 8  wherein the segments are disposed adjacent only the regions that undergo substantial bending, flexing, stretching, compressing upon the expansion of the scaffold.  
     
     
         14 . A device as in  claim 8  wherein the areas exhibiting relatively higher mechanical profile are configured to be in a direct flow of body fluids flowing through the intracorporeal body.  
     
     
         15 . A device as in  claim 8  further comprising a rate-controlling element disposed adjacent the scaffold.  
     
     
         16 . A device as in  claim 15  wherein the rate-controlling element is disposed adjacent at least a portion of the source.  
     
     
         17 . A device as in  claim 15  wherein the rate-controlling element is formed from a nonporous material.  
     
     
         18 . A device as in  claim 15  wherein the rate-controlling element has a variable thickness.  
     
     
         19 . A device as in  claim 15  wherein the rate-controlling element has a greater thickness adjacent scaffold regions having relatively higher mechanical profile.  
     
     
         20 . A device for intracorporeal use within a patient's body, comprising: 
 an implantable scaffold;    at least one source of at least one therapeutic capable agent associated with at least a portion of the scaffold and configured to release the therapeutic capable agent within the patient's body; and    a rate-controlling element disposed adjacent at least a portion of the source and including at least one disruption sufficiently large to permit material transport to or from the source.    
     
     
         21 . A device as in  claim 20  wherein the at least one disruption is an aperture.  
     
     
         22 . A device as in  claim 20  wherein the at least one disruption is preformed.  
     
     
         23 . A device as in  claim 20  wherein the at least one disruption is formed in the patient's body.  
     
     
         24 . A device as in  claim 20  wherein the transport comprises at least one of transport of native fluids to the source or of the therapeutic capable agent from the source.  
     
     
         25 . A device for intracorporeal use within a patient's body, comprising: 
 an implantable scaffold;    at least one source of at least one therapeutic capable agent associated with at least a portion of the scaffold and configured to release the therapeutic capable agent within the patient's body; and    a rate-controlling element disposed adjacent at least a portion of the source and being configured to mechanically change upon application of mechanical stress or strain.    
     
     
         26 . A device as in  claim 25  wherein the mechanical stress or strain is applied upon the bending of the scaffold.  
     
     
         27 . A device as in  claim 25  wherein the mechanical stress or strain is applied upon the expansion of the scaffold.  
     
     
         28 . A device for intracorporeal use within a patient's body, comprising: 
 an implantable scaffold;    at least one source of at least one therapeutic capable agent associated with at least a portion of the scaffold and configured to release the therapeutic capable agent within the patient's body; and    a rate-controlling element disposed adjacent at least a portion of the source and which undergoes a mechanical change upon being implanted in the patient's body.    
     
     
         29 . A device as in  claim 25  or  28  wherein the mechanical change is one of mechanical fracture.  
     
     
         30 . A device as in  claim 25  or  28  wherein the mechanical change is one of change in surface characteristic.  
     
     
         31 . A device as in  claim 25  or  28  wherein the mechanical change is one of change in porosity.  
     
     
         32 . A device as in any one of claims  8 ,  20 , or  25  wherein the device comprises a stent.  
     
     
         33 . A device as in  claim 32  wherein the source comprises a matrix.  
     
     
         34 . A device as in  claim 33  wherein the matrix includes a matrix material.  
     
     
         35 . A luminal prosthesis comprising: 
 a scaffold which is implantable within a body lumen;    a substance-containing reservoir positioned over at least a portion of a surface of the scaffold; and    a rate-controlling element layer covering at least a portion of the substance-containing reservoir, the rate-controlling element layer having the substance dispersed therein and providing for an initial rapid release of the substance from the rate-controlling element layer as well as a sustained, controlled release of the substance from the reservoir.    
     
     
         36 . A luminal prosthesis comprising: 
 a scaffold which is implantable in a body lumen, said scaffold being radially expansible and having regions which undergo greater and lesser mechanical stress or strain during radial expansion; and    a substance-containing reservoir or layer comprising individual portions which are preferentially positioned over the regions which undergo lesser stress or strain.    
     
     
         37 . A luminal prosthesis as in  claim 36  wherein the substance-containing layer is positioned only on those portions of the scaffold that do not substantially bend, stretch, or compress when the scaffold is expanded.  
     
     
         38 . A luminal prosthesis as in  claim 36  further comprising a rate-controlling element layer formed over at least a portion of the scaffold.  
     
     
         39 . A luminal prosthesis as in  claim 38  wherein the rate-controlling element layer is thicker over regions of greater mechanical profile.  
     
     
         40 . A luminal prosthesis comprising: 
 a scaffold which is implantable within a body lumen;    a substance-containing reservoir positioned over at least a portion of a surface of the scaffold; and    a rate-controlling element layer covering at least a portion of the substance-containing reservoir, the rate-controlling element layer having at least one preformed aperture which is sufficiently large to permit the transport of body fluids to the substance-containing reservoir and/or the release of substance from the reservoir.    
     
     
         41 . A luminal prosthesis comprising: 
 a scaffold which is implantable within a body lumen;    a substance-containing reservoir positioned over at least a portion of a surface of the scaffold, and    a rate-controlling element layer covering at least a portion of the substance containing reservoir, the rate-controlling element layer being configured to fracture when stressed by substantially bending, expanding, stretching, or compressing of the scaffold.    
     
     
         42 . A luminal prosthesis comprising: 
 a scaffold which is implantable within a body lumen;    a substance-containing reservoir positioned over at least a portion of a surface of the scaffold; and    a rate-controlling element layer covering at least a portion of the substance containing reservoir, the rate-controlling element layer being configured to swell to permit release of substance from the reservoir when exposed to a luminal environment.    
     
     
         43 . A luminal prosthesis comprising: 
 a scaffold which is implantable within a body lumen;    a substance-containing reservoir positioned over at least a portion of a surface of the scaffold; and    a rate-controlling element positioned over at least a portion of the surface of the scaffold and covering less than all of the substance containing reservoir.    
     
     
         44 . A luminal prosthesis as in any of claims  35  through  43  wherein the luminal prosthesis comprises a metal stent.  
     
     
         45 . A luminal prosthesis as in  claim 44  wherein the metal stent is balloon expandable.  
     
     
         46 . A luminal prosthesis as in  claim 44  wherein the metal stent is self-expanding.  
     
     
         47 . A luminal prosthesis as in any of claims  35  through  43  wherein the substance-containing reservoir comprises a matrix layer including the substance dispersed in a matrix material.  
     
     
         48 . A luminal prosthesis as in  claim 47  wherein the substance and the matrix material have been vapor deposited on the scaffold.  
     
     
         49 . A luminal prosthesis as in any of  claim 35  through  43  wherein the substance-containing layer consists essentially of a homogeneous layer of the substance.  
     
     
         50 . A luminal prosthesis as in  claim 49  wherein the substance has been vapor deposited on the scaffold.  
     
     
         51 . A luminal prosthesis as in any of claims  35  through  43  wherein the scaffold comprises structural elements having rectangular cross-sections defining four orthogonal surfaces, wherein the drug is positioned on fewer than all of the surfaces.  
     
     
         52 . A luminal prosthesis as in any of claims  35  through  43  wherein the rate-controlling element is porous.  
     
     
         53 . A luminal prosthesis as in any of  claim 35  through  43  wherein the rate-controlling element is nonporous.  
     
     
         54 . A luminal prosthesis as in any of claims  35  through  43  further comprising a base layer over at least a portion of the scaffold and at least a portion of the substance-containing layer.  
     
     
         55 . A luminal prosthesis as in any of claims  35  through  43  wherein the rate-controlling element layer comprises a parylene polymer or copolymer.  
     
     
         56 . A luminal prosthesis as in  claim 55  wherein the parylene has been vapor deposited over the scaffold or a portion thereof.  
     
     
         57 . A luminal prosthesis as in  claim 55  wherein the parylene comprises parylene C.  
     
     
         58 . A luminal prosthesis as in  claim 55  wherein the parylene is nonporous.  
     
     
         59 . A method for making a device for intracorporeal use, comprising: 
 providing an implantable structure having a first residual stress and including    a scaffold; and    at least one source of at least one therapeutic capable agent associated with the scaffold and configured to release the therapeutic capable agent at a targeted tissue site within the patient's body;    changing the structure residual stress to a second residual stress;    disposing a rate-controlling element adjacent at least a portion of the source and being configured to control the release of the therapeutic capable agent in the patient's body.    
     
     
         60 . A method as in  claim 59  wherein the changing step comprises reducing the residual stress.  
     
     
         61 . A method as in  claim 59  wherein the changing step comprises exposing the structure to ultrasound energy for a period of time.  
     
     
         62 . A method as in  claim 59  wherein the changing step comprises exposing the structure to vibrational energy for a period of time.  
     
     
         63 . A method as in  claim 59  wherein the changing step comprises heating the structure to a first temperature for a period of time.  
     
     
         64 . A method as in  claim 63  wherein the first temperature is less than the melting point of the therapeutic capable agent.  
     
     
         65 . A method as in  claim 63  wherein the first temperature is about the same as the melting point of the therapeutic capable agent.  
     
     
         66 . A method as in  claim 63  wherein the at least one therapeutic capable agent comprises a plurality of therapeutic capable agents and the first temperature is about the same as the melting point of the therapeutic capable agent with the lowest melting point.  
     
     
         67 . A method as in  claim 63  wherein the first temperature is more than the melting point of the therapeutic capable agent.  
     
     
         68 . A method as in  claim 63  wherein the at least one therapeutic capable agent comprises a plurality of therapeutic capable agents and the first temperature is more than the melting point of the therapeutic capable agent with the lowest melting point.  
     
     
         69 . A method as in  claim 63  wherein the first temperature is about the glass transition temperature of the rate-controlling element.  
     
     
         70 . A method as in  claim 63  wherein the first temperature is more than the glass transition temperature of the rate-controlling element  
     
     
         71 . A method as in  claim 59  wherein the changing step is performed before the disposing step.  
     
     
         72 . A method as in  claim 59  wherein the changing step is performed after the disposing.  
     
     
         73 . A method as in  claim 59  wherein the changing step comprises heating the structure to a second temperature for a period of time and is performed after the disposing step.  
     
     
         74 . A method as in  claim 73  wherein the heating of the structure to a second temperate is performed under vacuum.  
     
     
         75 . A method as in  claim 73  wherein the heating of the structure to a second temperate is performed in the absence of oxygen.  
     
     
         76 . A method as in  claim 73  wherein the second temperature is less than the glass transition temperature of the rate-controlling element.