Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment

Abstract

A mechanical dilatation and medicament delivery device for enlarging a flow passage of a vessel by dilating and delivering a charged paclitaxel analogue therapeutic agent or medicament to an obstruction in the vessel. The present invention comprises a substantially cylindrically shaped expansion member and includes a means engaged to the expansion member for altering the distance between the proximal end and the distal end of the expansion member thereby transforming the expansion member between a diametrically contracted configuration to diametrically expanded configuration. A charged paclitaxel analogue therapeutic agent or medicament is coated on either the expansion member, or combined/incorporated into a substrate coated on the expansion member. The present method comprises the steps of advancing the coated expansion member to the obstruction in a vessel and applying opposed forces on said expansion member in an axial direction to move the expansion member to an expanded configuration wherein the expansion member dilates the obstruction and the expansion member either passively or actively delivers a charged paclitaxel analogue therapeutic agent or medicament to the obstruction.

1 . An apparatus for dilating and delivering a medicament to an obstruction within a vascular segment or a body passageway which comprises: 
 a catheter having a distal end and a proximal end;    a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;    an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and    a paclitaxel analogue medicament coated on at least a portion of said expansion member.    
   
   
       2 . An apparatus as recited in  claim 1  wherein said paclitaxel analogue medicament is electrically charged.  
   
   
       3 . An apparatus as recited in  claim 2  wherein said charged paclitaxel analogue medicament has a negative charge.  
   
   
       4 . An apparatus as recited in  claim 2  wherein said charged paclitaxel analogue medicament has a positive charge.  
   
   
       5 . An apparatus as recited in  claim 1  wherein said paclitaxel analogue medicament is a compound known as TX-67.  
   
   
       6 . An apparatus as recited in  claim 1  wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.  
   
   
       7 . An apparatus as recited in  claim 1  wherein said expansion member comprises a first plurality of flexible elongate elements helically wound in a first direction of rotation and a second plurality of flexible elongate elements helically wound in a second direction of rotation to form a braid.  
   
   
       8 . An apparatus as recited in  claim 1  wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first diameter or in said second diameter.  
   
   
       9 . An apparatus as recited in  claim 1  wherein said paclitaxel analogue medicament is incorporated into a non-therapeutic substrate.  
   
   
       10 . The apparatus of  claim 9 , wherein said non-therapeutic substrate is selected from the group consisting of polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, hydrogels, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenated polyalkylenes including polytetrafluoroethylene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers as well as other biodegradable, bioabsorbable and biostable polymers and copolymers, coatings from polymer dispersions such as polyurethane dispersions and acrylic latex dispersions, protein polymers, fibrin, collage and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives of these polysaccharides, an extracellular matrix component, hyaluronic acid, or another biologic agent, and mixtures and copolymers thereof  
   
   
       11 . An apparatus for dilating and introducing molecules into cells within a vascular segment or a body passageway which comprises: 
 a catheter having a distal end and a proximal end;    a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;    an altering means engagable to said expansion member for moving said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and    a paclitaxel analogue medicament coated on at least a portion of said expansion member.    
   
   
       12 . An apparatus as recited in  claim 11  wherein said paclitaxel analogue medicament is electrically charged.  
   
   
       13 . An apparatus as recited in  claim 11  wherein said charged paclitaxel analogue medicament has a negative charge.  
   
   
       14 . An apparatus as recited in  claim 11  wherein said charged paclitaxel analogue medicament has a positive charge.  
   
   
       15 . An apparatus as recited in  claim 11  wherein said paclitaxel analogue medicament is a compound known as TX-67.  
   
   
       16 . A mechanical dilatation and medicament delivery device comprising: 
 a catheter having a distal end and a proximal end, said catheter having one or more lumens;    an substantially cylindrically shaped expandable mesh positioned on said distal end adapted to dilate an obstruction in a vessel, said mesh having a first contracted diameter and a second expanded diameter, said second expanded diameter being larger than said first contracted diameter; and    said mechanical dilatation and medicament delivery device being adapted to dilate said obstruction and expose said obstruction to a paclitaxel TX-67 analogue medicament while allowing blood or bodily fluids to flow through said substantially cylindrically shaped expandable mesh.    
   
   
       17 . A mechanical dilatation and medicament delivery device as recited in  claim 16  wherein said paclitaxel TX-67 analogue medicament is electrically charged.  
   
   
       18 . A mechanical dilatation and medicament delivery device as recited in  claim 17  wherein said charged TX-67 paclitaxel analogue medicament has a negative charge.  
   
   
       19 . A mechanical dilatation and medicament delivery device as recited in  claim 17  wherein said charged TX-67 paclitaxel analogue medicament has a positive charge.  
   
   
       20 . A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of: 
 advancing a mechanical dilatation and drug delivery catheter to a predetermined site with a body passageway, said catheter having an substantially cylindrical expansion member coated with a medicament, said expansion member being moveable between a first contracted configuration wherein said expansion member is defined by a first dimension extending in a radial direction, and a second expanded configuration wherein said member is defined by a second dimension extending in said radial direction;    applying a force on said coated expansion member in an axial direction to move said expansion member between said first contracted configuration to said second expanded configuration wherein said expansion member dilates said obstruction or body passageway and delivers a paclitaxel analogue medicament to an said obstruction or body passageway.    
   
   
       21 . The method as recited in  claim 20  wherein said paclitaxel analogue medicament is electrically charged.  
   
   
       22 . The method as recited in  claim 21  wherein said charged paclitaxel analogue medicament has a negative charge.  
   
   
       23 . The method as recited in  claim 21  wherein said charged paclitaxel analogue medicament has a positive charge.  
   
   
       24 . The method as recited in  claim 20  wherein said paclitaxel analogue medicament is a compound known as TX-67.  
   
   
       25 . The method as recited in  claim 20  which further comprises the step of positioning a guidewire in the body passageway, and wherein said advancing step is accomplished by threading said expansion member over said guidewire.  
   
   
       26 . The method as recited in  claim 20  which further comprises the step of allowing said expansion member to be in said second expanded configuration for a predetermined period of time after the dilatation step to further expose said obstruction to the medicament.  
   
   
       27 . The method as recited in  claim 20  wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first contracted configuration or in said second expanded configuration.  
   
   
       28 . An apparatus for dilating and delivering a medicament to an obstruction within a vascular segment or a body passageway which comprises: 
 a catheter having a distal end and a proximal end;    a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;    an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter;    one or more electrical leads extending throughout the longitudinal length of said catheter and engaged to said expansion member; and    a paclitaxel analogue medicament coated on a portion of said expansion member.    
   
   
       29 . An apparatus as recited in  claim 28  wherein said paclitaxel analogue medicament is electrically charged.  
   
   
       30 . An apparatus as recited in  claim 29  wherein said charged paclitaxel analogue medicament has a negative charge.  
   
   
       31 . An apparatus as recited in  claim 29  wherein said charged paclitaxel analogue medicament has a positive charge.  
   
   
       32 . An apparatus as recited in  claim 28  wherein said paclitaxel analogue medicament is a compound known as TX-67.  
   
   
       33 . An apparatus as recited in  claim 28  wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.  
   
   
       34 . An apparatus as recited in  claim 28  wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first diameter or in said second diameter.  
   
   
       35 . An apparatus as recited in  claim 28 , wherein said electrical leads can communicate electrical energy to said expansion member to compel said paclitaxel analogue medicament into target tissues by iontophoretic means.  
   
   
       36 . An apparatus as recited in  claim 28 , wherein said electrical leads can communicate electrical energy to said expansion member to compel electroporation transfer of said paclitaxel analogue medicament into target tissues.  
   
   
       37 . An apparatus as recited in  claim 28 , wherein said electrical leads can communicate electrical energy to said expansion member to cause both iontophoretic and electroporation transfer of said paclitaxel analogue medicament into target tissues.  
   
   
       38 . An apparatus as recited in  claim 28 , wherein said electrical leads can communicate electrical energy to said expansion member to cause said paclitaxel analogue medicament to electrically bond to said expansion member.  
   
   
       39 . An apparatus as recited in  claim 28  wherein said therapeutic agent or medicament is incorporated into a non-therapeutic substrate.  
   
   
       40 . The apparatus of  claim 39 , wherein said non-therapeutic substrate is selected from the group consisting of polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, hydrogels, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenated polyalkylenes including polytetrafluoroethylene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers as well as other biodegradable, bioabsorbable and biostable polymers and copolymers, coatings from polymer dispersions such as polyurethane dispersions and acrylic latex dispersions, protein polymers, fibrin, collage and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives of these polysaccharides, an extracellular matrix component, hyaluronic acid, or another biologic agent, and mixtures and copolymers thereof  
   
   
       41 . A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of: 
 advancing a mechanical dilatation catheter to a predetermined site with a body passageway, said catheter having an expansion member coated with a paclitaxel analogue medicament and a iontophoretic transport means, said expansion member being moveable between a first contracted configuration wherein said member is defined by a first dimension extending in a radial direction, and a second expanded configuration wherein said member is defined by a second dimension extending in said radial direction;    applying a force on said expansion member in an axial direction to move said expansion member between said first contracted configuration to said second expanded configuration wherein said obstruction is dilated;    supplying a flow of electrical current to said iontophoretic means to deliver said paclitaxel analogue medicament into said obstruction or body passageway.    
   
   
       42 . The method as recited in  claim 41  which further comprises the step of positioning a guidewire in the body passageway, and wherein said advancing step is accomplished by threading said catheter over said guidewire.  
   
   
       43 . The method as recited in  claim 41  wherein said paclitaxel analogue medicament is electrically charged.  
   
   
       44 . The method as recited in  claim 43  wherein said charged paclitaxel analogue medicament has a negative charge.  
   
   
       45 . The method as recited in  claim 43  wherein said charged paclitaxel analogue medicament has a positive charge.  
   
   
       46 . The method as recited in  claim 41  wherein said paclitaxel analogue medicament is a compound known as TX-67.  
   
   
       47 . The method as recited in  claim 41  which further comprises the step of allowing said expansion member to be in said second expanded configuration for a predetermined period of time after the dilatation step to further expose said obstruction to the medicament.  
   
   
       48 . The method as recited in  claim 41  wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first contracted configuration or in said second expanded configuration.  
   
   
       49 . The method as recited in  claim 41  which further comprises the step of varying the electric current with time to provide a waveform that controls the rate of iontophoretic transport of said medicament.  
   
   
       50 . The method as recited in  claim 41 , further comprising, prior to advancing the catheter, the step of applying electrical energy to said expansion member to cause said medicament or therapeutic agent to electrically bond to said expansion member.