High concentration medicament and polymer coated device for passive diffusional medicament delivery

Abstract

The present invention relates to a catheter with an expandable distal end for delivering one or more medicaments. The catheter also has a means for controlling or manipulating the expandable distal end to expand and contract into various configurations to apply pressure and achieve good contact against the walls of structures into which it is advanced. The distal end of the catheter is processed by a specific method of manufacturing whereby the expandable distal end is coated with one or more layers of a polymer wherein the surface layer of which coating carries one or more medicaments at very high concentration and zero or more excipients to facilitate the diffusional penetration of the medicaments into contacted tissues.

1 . An apparatus for delivering a therapeutic agent or medicament comprising: 
 a catheter with an expandable portion having a surface adapted to contract a vessel wall when in an expanded condition, said expandable portion having a perfusion means therein to allow blood flow through the expandable portion;    a first flexible polymer coating on the expandable portion;    a second coating on the expandable portion, disposed substantially over the first flexible polymer, said second coating having a therapeutic agent or medicament to polymer ratio of at least 4 to 1 by weight.    
   
   
       2 . An apparatus as recited in  claim 1  further comprising one or more excipients interacting with said polymer incorporating one or more therapeutic agents or medicaments.  
   
   
       3 . An apparatus as recited in  claim 1 , wherein said catheter with polymer retaining a high concentration therapeutic agent or medicament will function to release the medicaments from the polymer into tissue by diffusional means.  
   
   
       4 . An apparatus as recited in  claim 1 , wherein said catheter with polymer carrying a therapeutic agent or medicament will function to deliver the medicaments into target tissues of said vascular segment or body passageway by diffusional means because of high concentration at the surface.  
   
   
       5 . An apparatus as recited in  claim 1 , wherein said therapeutic agent or medicament is a compound that inhibits cellular proliferation, paclitaxel and paclitaxel derivatives or rapamycin and rapamycin derivatives, and any combinations thereof.  
   
   
       6 . An apparatus as recited in  claim 1 , wherein said therapeutic agent or medicament will migrate into target tissues when exposed to a high concentration of the drug at the surface.  
   
   
       7 . An apparatus as recited in  claim 1 , further comprising a solvent that rapidly evaporates and exposes a crystalline therapeutic agent or medicament.  
   
   
       8 . An apparatus as recited in  claim 1 , wherein said therapeutic agent or medicaments crystallize and become exposed on the surface of said expansion member.  
   
   
       9 . An apparatus as recited in  claim 1 , wherein said therapeutic agent or medicament is a combination of one or more medicaments.  
   
   
       10 . An apparatus as recited in  claim 1 , wherein said catheter coated with a therapeutic agent or medicament and polymer matrix is an over-the wire design.  
   
   
       11 . An apparatus as recited in  claim 1 , wherein said catheter coated with a therapeutic agent or medicament and polymer matrix employs a rapid exchange design.  
   
   
       12 . An apparatus as recited in  claim 1  further comprised by a first contracted configuration and a second expanded configuration wherein said expandable distal end is adapted to allow blood perfusion while said expandable distal is in either in said first contracted configuration or in said second expanded configuration.  
   
   
       13 . An apparatus as recited in  claim 1 , further comprising said first polymer having a low drug content such that the flexibility of the first flexible polymer is not substantially degraded.  
   
   
       14 . An apparatus as recited in  claim 1  wherein said apparatus is coated with a first flexible polymer without a medicament or excipient, said first flexible polymer is substantially coated with a very high medicament concentration of a solvent that has a rate of evaporation to promote high drug deposition at the surface.  
   
   
       15 . A drug delivery device comprising; 
 a catheter having an expandable portion having a surface adapted to substantially contact a vessel wall when in a expanded condition; said expandable portion have a perfusion means therein to allow blood flow through the expandable position; and    paclitaxel or paclitaxel derivative disposed on the surface of the expandable portion, said coated expandable portion having some crystalline paclitaxel or paclitaxel derivative disposed on the surface said coated expandable portion.    
   
   
       16 . A drug delivery device comprising; 
 a catheter having an expandable portion having a surface adapted to substantially contact a vessel wall when in a expanded condition; said expandable portion have a perfusion means therein to allow blood flow through the expandable position; and    rapamycin or rapamycin derivative disposed on the surface of the expandable portion, said coated expandable portion having some crystalline rapamycin or rapamycin derivative disposed on the surface said coated expandable portion.    
   
   
       17 . A method for introducing encapsulated medicaments into cells of a patient, comprising the steps of: 
 selecting as an elongated catheter a substantially cylindrical shaped expansion member located on a distal end, 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; said expansion member having at least one coating, an outer coating having a therapeutic agent or medicament to polymer ratio of at least 4 to 1 by weight;    locating said catheter into a selected blood vessel or other lumenal physiological structure of a patient;    expanding said cylindrical expansion member wherein a portion of said cylindrical expansion member contacts the vessel wall at a predetermined location;    
   
   
       18 . A method for delivering a medicament to an obstruction in a body passageway which comprises the steps of: 
 advancing a polymer coated device for diffusional mediated drug delivery to a predetermined site with a body passageway, said catheter having an substantially cylindrical expansion member coated with a high concentration of a therapeutic agent or 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 the therapeutic agent or medicament firmly against said obstruction or body passageway.    
   
   
       19 . A method as recited in  claim 18  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.  
   
   
       20 . A method as recited in  claim 18  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.  
   
   
       21 . A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of: 
 advancing a polymer coated device for diffusion mediated drug delivery to a predetermined site within a body passageway, said device having an expansion member coated with a polymer and a crystalline medicament, 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;    applying a pressure against the tissue to deliver the crystalline medicament into said obstruction or body passageway.    
   
   
       22 . A method as recited in  claim 21  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.  
   
   
       23 . A method as recited in  claim 21  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.  
   
   
       24 . An apparatus for delivering a medicament to an obstruction within a vascular segment or a body passageway which comprises: 
 a catheter with an expandable mechanical distal end;    said distal end incorporating a polymer carrying one or more medicaments at high surface concentrations,    a medicament formulation that does not release significant drug into the systemic circulation, and    a medicament formulation and polymer that upon wetting and flexing the apparatus causes a portion of the medicament formulation to crystallize and to become exposed at the surface of the expandable mechanical distal end and increase exposure to the tissue.    
   
   
       25 . An apparatus as recited in  claim 24 , wherein said catheter with polymer carrying a therapeutic agent or medicament will function to release the medicaments from the polymer by diffusional means.  
   
   
       26 . An apparatus as recited in  claim 24 , wherein said catheter with polymer encapsulating a therapeutic agent or medicament will function to deliver the medicaments into target tissues of said vascular segment or body passageway by diffusional means.  
   
   
       27 . An apparatus as recited in  claim 24 , wherein said therapeutic agent or medicament is a compound that inhibits cellular proliferation, paclitaxel and paclitaxel derivatives or rapamycin and rapamycin derivatives, and any combinations thereof.  
   
   
       28 . An apparatus as recited in  claim 24 , wherein said polymer carried agent or medicament is a combination of one or more medicaments.  
   
   
       29 . An apparatus as recited in  claim 24 , wherein said catheter with polymer carrying a therapeutic agent or medicament is an over-the wire design.  
   
   
       30 . An apparatus as recited in  claim 24 , wherein said catheter with polymer carrying a therapeutic agent or medicament employs a rapid exchange design.  
   
   
       31 . An apparatus as recited in  claim 24 , further comprised by a first contracted configuration and a second expanded configuration wherein said expandable distal end is adapted to allow blood perfusion while said expandable distal end is either in said first contracted configuration or in said second expanded configuration.  
   
   
       32 . An apparatus as recited in  claim 24 , wherein said expandable distal end can perform dilatation and drug delivery while simultaneously allow blood perfusion.  
   
   
       33 . An apparatus as recited in  claim 24 , wherein said crystalline medicament formulation is paclitaxel or a paclitaxel derivative.  
   
   
       34 . An apparatus as recited in  claim 24 , wherein said crystalline medicament formulation is rapamycin or a rapamycin derivative.  
   
   
       35 . A method for coated a stent with multiple coatings: 
 employing a water based solvent to incorporate one or more medicaments into a polymer to comprise a first base coating;    coating a portion of the distal expandable end of a drug delivery catheter with said first base coating;    employing an organic based solvent to incorporate one or more medicament into a polymer to comprise a second top coating, said second top coating having medicament to polymer ratio of at least 4 to 1 by weight;    coating said second top coating substantially over said first base coating.    
   
   
       36 . A method as recited in  claim 35 , further comprising that said water based solvent is H 2 O, ethanol or any alcohol derivative, or any combination of H 2 O, ethanol or any alcohol derivative thereof.  
   
   
       37 . A method as recited in  claim 35 , further comprising that said organic based solvent is tetrahydrofuran or toluene, or any combination of tetrahydorfuran and toluene thereof.