LOADING AND RELEASE OF WATER-INSOLUBLE DRUGS

• US 20110196340A1
• Filed: 04/13/2011
• Published: 08/11/2011
• Est. Priority Date: 08/13/1997
• Status: Abandoned Application

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Barry, James J., Palasis, Maria
• Application Number:
  US13/085,623
• Publication Number:
  US 20110196340A1
• Time in Patent Office: Days
• US Class Current: 604/509
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• 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 2025/1081 having sheaths or the like for covering the balloon but not forming a permanent part of the balloon, e.g. retractable, dissolvable or tearable sheaths
• CPC Class Codes: A61M 2025/1088 having special surface characteristics depending on material properties or added substances, e.g. for reducing friction
• 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 25/1027 Making of balloon catheters
• CPC Class Codes: A61M 29/02 : Dilators made of swellable material balloon catheters for angioplasty A61M25/104
• CPC Class Codes: C08L 33/08 : Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 75/04 : Polyurethanes

Abstract

A medical device, polymer composition, and method for delivering substantially water-insoluble drugs to tissue at desired locations within the body. At least a portion of the exterior surface of the medical device is provided with a polymer coating. Incorporated in the polymer coating is a solution of at least one substantially water-insoluble drug in a volatile organic solvent. The medical device is positioned to a desired target location within the body, whereupon the drug diffuses out of the polymer coating.

Claims

1. A method of preparing an angioplasty balloon catheter having a balloon with an exterior surface, the method comprising:

mixing at least one drug with a volatile solvent to create a drug solution, the at least one drug comprising paclitaxel and the volatile solvent comprising at least one volatile organic solvent optionally in mixture with water;

applying said drug solution to said exterior surface of the balloon, and

evaporating the volatile solvent.

2. The method of claim 1, wherein said drug mixture is applied by dipping, or spraying.

3. The method of claim 1 wherein a predetermined amount of said solution of known concentration is applied to the balloon to provide a balloon with a predetermined loading of paclitaxel thereon.

4. The method of claim 3 wherein the solution is applied from a pipette.

5. The method of claim 1, wherein said volatile solvent comprises ethanol.

6. The method of claim 1, wherein said volatile solvent is a mixture of a volatile organic solvent and water.

7. The method of claim 1, wherein said at least one drug consists of paclitaxel.

8. The method of claim 1, further comprising the step of applying a modulating layer comprising a polymer to said balloon after evaporating said solvent.

9. The method of claim 8, wherein the modulating layer has a thickness of about 50 to about 5000 Angstroms.

10. The method of claim 9, wherein the modulating layer has a thickness of about 50-2000 Angstroms.

11. The method of claim 8, wherein said modulating layer further comprises a drug.

12. The method of claim 13 wherein the modulating layer comprises a silicone.

13. The method of claim 1 wherein said at least one drug comprising paclitaxel further comprises a second drug selected from the group consisting of anticoagulants, anti-inflammatory agents, antimitotics, antithrombogenics, thrombolytics, nitric oxide-containing polymers, vascular cell promoters, growth factors, and mixtures thereof.

14. The method of claim 1 wherein the at least one drug further comprises a member of the group consisting of dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, mesalamine, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, thymidine kinase inhibitors, lidocaine, bupivacaine, ropivacaine, and mixtures thereof.

15. The method of claim 1 wherein the drug solution is applied to the balloon while the balloon is in a substantially deflated state.

16. The method of claim 1 wherein the drug solution is applied to the balloon while the balloon is in an inflated state.

17. The method of claim 1 wherein total amount of paclitaxel on the balloon after evaporating said volatile solvent is in the range of from about 200 to about 1532 μ

g.

18. A method of preparing an angioplasty balloon catheter having a balloon with an exterior surface, the method comprising:

mixing at least one drug with a volatile solvent to create a drug solution, the at least one drug selected from the group consisting of paclitaxel dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, mesalamine, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, thymidine kinase inhibitors, lidocaine, bupivacaine, ropivacaine, and mixtures thereof, and the volatile solvent comprising at least one volatile organic solvent optionally in mixture with water;

applying said drug solution to said exterior surface of the balloon, and

evaporating the volatile solvent.

19. A method of delivering paclitaxel, to an inner wall of a blood vessel of a patient from an angioplasty catheter having an expandable balloon with the paclitaxel on an outer surface of the balloon, the method comprising:

providing a balloon of a balloon catheter having a layer consisting of dried paclitaxel on the outer surface of the balloon; and

employing the catheter for vessel dilatation.

20. A method of delivering paclitaxel to an inner wall of a blood vessel the method comprising:

providing a balloon catheter having a balloon an outer surface and a dried layer containing the paclitaxel on the outer surface of the balloon;

advancing the balloon within the blood vessel to a treatment site within the blood vessel;

inflating the balloon at the treatment site to contact the balloon with an inner wall of the blood vessel; and

maintaining the inflated balloon in contact with the inner wall of the blood vessel so as to transfer paclitaxel to the inner wall of the blood vessel.

21. The method of claim 20, wherein the blood vessel is a coronary artery.

22. The method of claim 20, wherein at said providing step, the implantable medical device includes a total of from about 152 to about 1532 μ

g of paclitaxel in said dried layer.

23. The method of claim 20, wherein the method is performed without implanting a stent within the blood vessel.

24. The method of claim 20, wherein the balloon comprises a material selected from the group consisting of:

a polyamide, polyolefins, polyesters and copolymers thereof.

25. The method of claim 20, wherein the dried layer consists essentially of about 200 to about 1532 μ

g of paclitaxel.

26. The method of claim 20, wherein the time the inflated balloon is in contact with the inner wall of the blood vessel corresponds to said maintaining step.

27. A method of delivering paclitaxel to an inner wall of a blood vessel from a balloon catheter having an expandable balloon with a coating on an outer surface of the balloon, the method comprising:

providing a balloon catheter including a balloon with a dried coating consisting of paclitaxel or a mixture of paclitaxel with another bioactive agent, the dried coating being free of any additional coating atop the dried coating;

advancing the balloon within the blood vessel to a treatment site;

inflating the balloon to directly contact the paclitaxel or mixture of paclitaxel with another bioactive agent with an inner wall of the blood vessel; and

delivering the paclitaxel or mixture of paclitaxel with another bioactive agent to the inner wall of the blood vessel while maintaining the paclitaxel or mixture of paclitaxel with another bioactive agent in direct contact with the inner wall of the blood vessel while the balloon is inflated.

28. The method of claim 27, where the balloon is attached to a catheter shaft that includes a guide wire lumen and an inflation lumen for inflating the balloon.

29. The method of claim 27, where the paclitaxel or mixture of paclitaxel with another bioactive agent is brought into direct contact with the vessel wall only while the outer surface of the inflated balloon is maintained in contact with the inner wall of the blood vessel.

30. The method of claim 29, where the method is performed without implanting a stent within the blood vessel.

31. A method of delivering paclitaxel to an interior wall of a blood vessel from a balloon catheter having an expandable balloon with a paclitaxel coating on an outer surface of the balloon, the method comprising:

providing a balloon catheter without a stent, the balloon catheter having a dried coating consisting of about 200 to about 1532 μ

g micrograms of a single bioactive coating material consisting of paclitaxel over the outer surface area of the balloon, the balloon catheter being free of any coating atop the paclitaxel, where amounts of the paclitaxel are deliverable to the interior wall upon direct contact of the paclitaxel with the interior wall, and where the balloon has been coated in an inflated state;

advancing the balloon in a deflated state within the blood vessel to a treatment site within the blood vessel; and

inflating the balloon at the treatment site to directly contact the paclitaxel in the coating with the interior wall of the blood vessel and thereby deliver paclitaxel to the interior wall without implanting a stent within the blood vessel.

32. A method of delivering paclitaxel to an inner wall of a blood vessel of a patient from an implantable medical device having an expandable balloon with the paclitaxel on an outer surface of the balloon, the method comprising the steps of:

providing an angioplasty balloon having a dried layer of coating material containing paclitaxel on the outer surface of the balloon, wherein the dried layer of coating material is the outermost layer on the balloon, wherein the balloon has folds, and wherein portions of the dried layer are positioned in the folds;

advancing the balloon within the blood vessel to a treatment site within the blood vessel;

inflating the balloon at the treatment site so as to cause the folds to open so that portions of the balloon come into contact with the inner wall of the blood vessel during which amounts of the coating material containing paclitaxel are transferred to the inner wall of the blood vessel;

maintaining the inflated balloon in contact with the inner wall of the blood vessel;

deflating the balloon after said maintaining; and

removing the deflated balloon from the blood vessel.

33. The method of claim 32, wherein the coating material consists essentially of paclitaxel.