Composition for intravascular delivery of therapeutic composition

Abstract

The present invention relates to a pharmaceutical composition for intravascular delivery of a therapeutic agent, such as paclitaxel, rapamycin, or an analog thereof. The composition includes the therapeutic agent and a biocompatible solvent, such as glycofurol. The composition can aid tissue penetration by the therapeutic agent. A catheter assembly that protects the pharmaceutical composition from the surroundings can be used for its intravascular delivery.

1 . A pharmaceutical composition comprising about 1 to about 50 wt-% therapeutic agent and about 50 to about 99 wt-% biocompatible solvent;
 wherein:   the therapeutic agent comprises paclitaxel, rapamycin, a rapalog, or a mixture thereof; and   the biocompatible solvent comprises glycofurol, ethyl heptanoate, ethyl octanoate, benzyl benzoate, glycerol tributyrate, dimethyl isosorbide, glycerol triacetate (triacetin), glycerol tributyrate, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), methanol, ethanol, isopropyl alcohol, dimethylformamide (DMF), dimethylacetamide (DMAC), or a mixture thereof.   
     
     
         2 . The composition of  claim 1 , comprising about 2 to about 30 wt-% paclitaxel and about 70 to about 98 wt-% glycofurol. 
     
     
         3 . The composition of  claim 1 , comprising about 10 to about 40 wt-% rapamycin or rapalog and about 60 to about 90 wt-% biocompatible solvent. 
     
     
         4 . An intravascular catheter comprising a reservoir; the reservoir containing a pharmaceutical composition comprising about 1 to about 50 wt-% therapeutic agent and about 50 to about 99 wt-% biocompatible solvent;
 wherein:   the therapeutic agent comprises paclitaxel, rapamycin, a rapalog, or a mixture thereof; and   the biocompatible solvent comprises glycofurol, ethyl heptanoate, ethyl octanoate, benzyl benzoate, glycerol tributyrate, dimethyl isosorbide, glycerol triacetate (triacetin), glycerol tributyrate, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), methanol, ethanol, isopropyl alcohol, dimethylformamide (DMF), dimethylacetamide (DMAC), or a mixture thereof.   
     
     
         5 . The catheter of  claim 4 , wherein the pharmaceutical composition comprises about 2 to about 30 wt-% paclitaxel and about 70 to about 98 wt-% glycofurol. 
     
     
         6 . The catheter of  claim 4 , wherein the pharmaceutical composition comprises about 10 to about 40 wt-% rapamycin or rapalog and about 60 to about 90 wt-% biocompatible solvent. 
     
     
         7 . The catheter of  claim 4 , wherein a third lumen defines the reservoir. 
     
     
         8 . The catheter of  claim 4 , wherein two balloons define the reservoir. 
     
     
         9 . The catheter of  claim 4 , wherein the catheter is a catheter assembly comprising:
 an inner expandable and collapsible structure, an outer expandable and collapsible structure, the inner and outer expandable and collapsible structures each being configured to expand between a contracted state and a dilated state;   the inner and outer expandable and collapsible structures defining a reservoir therebetween, the reservoir being configured to contain a benefit composition;   the outer expandable and collapsible structure defining openings, the openings being configured to be closed when the assembly is in the contracted state and open when the assembly is in the dilated state; when open, the openings provide fluid communication from the cavity to surroundings of the assembly.   
     
     
         10 . A method of delivering a therapeutic agent to a site in a body, the method
 comprising: placing at the site the catheter of  claim 4 ; and   releasing the therapeutic agent at the site.   
     
     
         11 . A method of delivering paclitaxel to a site in a body, the method comprising:
 placing at the site the catheter of  claim 9 ; and   releasing the paclitaxel at the site.   
     
     
         12 . A pharmaceutical composition comprising about 1 to about 50 wt-% biodegradable polymer and about 50 to about 99 wt-% biocompatible solvent;
 wherein the biocompatible solvent comprises glycofurol, ethyl heptanoate, ethyl octanoate, benzyl benzoate, glycerol tributyrate, dimethyl isosorbide, glycerol triacetate (triacetin), glycerol tributyrate, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), methanol, ethanol, isopropyl alcohol, dimethylformamide (DMF), dimethylacetamide (DMAC), or a mixture thereof.   
     
     
         13 . An intravascular catheter comprising a reservoir; the reservoir containing a pharmaceutical composition comprising about 1 to about 50 wt-% biodegradable polymer and about 50 to about 99 wt-% biocompatible solvent;
 wherein the biocompatible solvent comprises glycofurol, ethyl heptanoate, ethyl octanoate, benzyl benzoate, glycerol tributyrate, dimethyl isosorbide, glycerol triacetate (triacetin), glycerol tributyrate, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), methanol, ethanol, isopropyl alcohol, dimethylformamide (DMF), dimethylacetamide (DMAC), or a mixture thereof.   
     
     
         14 . A method of delivering a biodegradable polymer to a site in a body, the method comprising:
 placing at the site the catheter of  claim 13 ; and   releasing the biodegradable polymer at the site.