Balloon catheter systems for delivery of dry drug delivery vesicles to a vessel in the body

• US 9,649,478 B2
• Filed: 04/07/2014
• Issued: 05/16/2017
• Est. Priority Date: 12/30/2009
• Status: Active Grant

• Current Assignee: Caliber Therapeutics, LLC
• Original Assignee: Caliber Therapeutics, Inc. (Orchestra Biomed Incorporated)
• Inventors: Baumbach, William R., Sherman, Darren R., Burgermeister, Robert S.
• Primary Examiner(s): Bosworth, Kami A
• Application Number:
  US14/247,057
• Publication Number:
  US 20140221978A1
• Time in Patent Office: 1,135 Days
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 29/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/1013 with concentrically mounted balloons, e.g. being independently inflatable
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2025/1075 having a balloon composed of several layers, e.g. by coating or embedding
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 25/1011 Multiple balloon catheters
• CPC Class Codes: A61M 25/1018 Balloon inflating or inflation-control devices
• CPC Class Codes: A61M 25/10182 Injector syringes
• CPC Class Codes: A61M 25/10185 Valves
• CPC Class Codes: A61M 25/10187 Indicators for the level of inflation or deflation
• CPC Class Codes: A61M 25/104 used for angioplasty

Abstract

Devices and methods for balloon delivery of rapamycin and other hydrophobic compounds to the wall of blood vessels. Balloon catheters, such as those used for balloon angioplasty, are modified with the addition of a reservoir of dry micelles, disposed at a suitable location within the balloon or catheter. The reservoir may be installed within the angioplasty balloon, within a lumen in communication with the angioplasty balloon, either as a loose or packed powder or as a film coating. The micelle preparation is reconstituted and the micelles are mobilized when the aqueous solution used to inflate the balloons is injected into the catheter. The micelles are infused into tissue surrounding the balloon when pressurized fluid within the balloon leaks through the wall of the balloon.

Claims

1. A method of treating a lesion in a blood vessel of a patient comprising:

providing balloon catheter system comprising;

a catheter body characterized by a distal portion and a proximal portion;

a first, outer, balloon disposed on the distal portion of the catheter body, said first, outer, balloon having a porous wall portion;

a reservoir of lyophilized micelles with rapamycin encapsulated in the micelles, said reservoir disposed within the first, outer, balloon

a reservoir of aqueous solution suitable for mobilizing the micelles within the micelle reservoir;

a first injection port disposed on the proximal portion of the catheter body; and

a first lumen communicating from the first injection port to the first, outer, balloon;

inserting the distal portion of the catheter body into the blood vessel such that the first, outer, balloon is disposed near the lesion; and

thereafter

filling the first, outer, balloon with the aqueous solution to wet and mobilize the micelles;

pressurizing the first, outer, balloon to force the micelles through the porous wall portion of the first, outer, balloon into the blood vessel.

2. The method of claim 1 further comprising the steps of:

providing the balloon catheter system with a second, inner, balloon disposed on the distal portion of the catheter body, within the first, outer, balloon, defining an inter-balloon space between the first, outer, balloon and the second, inner, balloon;

a second injection port disposed on the proximal portion of the catheter body;

a second lumen communicating from the second injection port to the second, inner, balloon;

wherein the micelle reservoir is disposed in the inter-balloon space between the first, outer, balloon and the second, inner, balloon; and

after filling the first, outer, balloon with the aqueous solution to wet and mobilize the micelles, inflating the second, inner, balloon to accomplish the step of pressurizing the first, outer, balloon to force the micelles through the porous wall portion of the first, outer, balloon into the blood vessel.

3. The method of claim 1 further comprising the steps of:

pressurizing the first, outer, balloon with the aqueous solution to wet and mobilize the micelles to perform angioplasty within the blood vessel.

4. The method of claim 2 further comprising the steps of:

pressurizing the first, outer, balloon with the aqueous solution to wet and mobilize the micelles to perform angioplasty within the blood vessel.

5. The method of claim 2 further comprising the steps of:

pressurizing the second, inner, balloon to perform angioplasty within the blood vessel.

6. The method of claim 2 further comprising the steps of:

pressurizing the first, outer, balloon to perform angioplasty within the blood vessel, and thereafter inflating the second, inner, balloon to pressurize the first, outer, balloon and thereby force micelles through the porous wall portion of the first, outer, balloon.

7. The method of claim 2 further comprising the steps of:

pressurizing the second, inner, balloon to perform angioplasty within the blood vessel, and thereafter deflating the second, inner, balloon and performing the step of filling the first outer balloon to wet and mobilize the micelles, and thereafter inflating the second, inner, balloon to pressurize the first, outer, balloon and thereby force the micelles through the porous wall portion of the first, outer, balloon.

8. The method of claim 2 further comprising the steps of:

providing the second, inner, balloon with a porous wall portion and the reservoir of lyophilized micelles disposed in the inter-balloon space defined between the first, outer, balloon and the second, inner, balloon;

pressurizing the second, inner, balloon with fluid from the reservoir of aqueous solution to perform angioplasty within the blood vessel, thereby forcing flow from the reservoir of aqueous solutions through the second, inner, balloon porous wall section and into the inter-balloon space to wet the micelle reservoir disposed in the inter-balloon space and flush the micelles through the porous wall portion of the first, outer, balloon.

9. The method of claim 1, wherein:

the porous wall portion of the first, outer, balloon has pores with a diameter of 0.1 to 5 microns;

the step of wetting and mobilizing the micelles is performed such that the micelles have a particle size of 40 to 250 nm; and

the step of pressuring the first, outer balloon, is performed to a pressure of 6 to 12 atmospheres.

10. The method of claim 9 further comprising the steps of:

providing the balloon catheter system with a second, inner, balloon disposed on the distal portion of the catheter body, within the first, outer, balloon, defining an inter-balloon space between the first, outer, balloon and the second, inner, balloon;

a second injection port disposed on the proximal portion of the catheter body;

a second lumen communicating from the second injection port to the second, inner, balloon;

wherein the micelle reservoir is disposed in the inter-balloon space between the first, outer, balloon and the second, inner, balloon; and

after filling the first, outer, balloon with the aqueous solution to wet and mobilize the micelles, inflating the second, inner, balloon to accomplish the step of pressurizing the first, outer, balloon to force the micelles through the porous wall portion of the first, outer, balloon into the blood vessel.

11. The method of claim 9 further comprising the steps of:

pressurizing the first, outer, balloon to perform angioplasty within the blood vessel.

12. The method of claim 10 further comprising the steps of:

pressurizing the first, outer, balloon to perform angioplasty within the blood vessel.

13. The method of claim 10 further comprising the steps of:

pressurizing the first, outer, balloon to perform angioplasty within the blood vessel, and thereafter inflating the second, inner, balloon to pressurize the first, outer, balloon and thereby force micelles through the porous wall portion of the first, outer, balloon.