Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens

• US 10,314,948 B2
• Filed: 04/24/2015
• Issued: 06/11/2019
• Est. Priority Date: 09/15/2008
• Status: Active Grant

• Current Assignee: Spectranetics Corporation (Koninklijke Philips N.V.)
• Original Assignee: Spectranetics Corporation (Koninklijke Philips N.V.)
• Inventors: Michal, Eugene T., Lerner, Daniel J., Pollman, Matthew J.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Mercier, Melissa S
• Application Number:
  US14/695,114
• Publication Number:
  US 20150224229A1
• Time in Patent Office: 1,509 Days
• Field of Search: None
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/141 Plasticizers
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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 25/104 used for angioplasty

Abstract

A method and device for local delivery of water-soluble or water-insoluble therapeutic agents to the surface of a normal or diseased body lumen is disclosed. An expandable structure of a medical disposable device, such as a balloon of a balloon catheter, is coated with an amphiphilic polymer coating comprising a therapeutic agent and an amphiphilic polymer or co-polymer. The medical disposable device is inserted into a body lumen, and expanded to contact the amphiphilic polymer coating against the body lumen. The total solubility of the polymer or co-polymer in vivo prevents any embolic hazard associated with the amphiphilic polymer coating.

Claims

1. A method comprising:

applying a polymeric composition to at least a portion of an outer surface of an expandable portion of a disposable medical device,

said polymeric composition including a hydrophobic therapeutic agent, a plasticizer, and an amphiphilic polymer or co-polymer complexed with iodine,

wherein said polymeric composition is applied by dip coating.

2. The method of claim 1, wherein the polymeric composition comprises an amphiphilic polymer or co-polymer selected from the group consisting of hydroxypropyl cellulose, poly (methyl vinyl ether-alt-maleic acid monobutyl ester), poly (methyl vinyl ether-alt-maleic acid monoethyl ester), and polyvinyl pyrrolidone.

3. The method of claim 1, wherein the polymeric composition comprises a plasticizer selected from the group consisting of polyethylene glycol with a molecular weight below 10 K Daltons, propylene glycol, triethyl citrate, glycerol, and dibutyl sebacate.

4. The method of claim 1, wherein the polymeric composition comprises a plasticizer at a concentration of less than 20% by weight of the at least one amphiphilic polymer or co-polymer complexed with iodine.

5. The method of claim 1, wherein the polymeric composition comprises a wax selected from the group consisting of bees wax, camauba wax, polydimethyl siloxane, and polydimethyl siloxane derivatives.

6. The method of claim 5, wherein the polymeric composition comprises a wax at a concentration of less than 1% by weight of said at least one amphiphilic polymer or co-polymer complexed with iodine.

7. The method of claim 1, wherein the polymeric composition comprises a hydrophobic therapeutic agent selected from the group consisting of anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, thrombolytic agents, and combinations thereof.

8. The method of claim 1, wherein the polymeric composition comprises a hydrophobic therapeutic agent selected from the group consisting of paclitaxel and dexamethasone acetate.

9. A method of coating a medical disposable device comprising:

providing a medical disposable device having an expandable portion; and

forming an amphiphilic polymer coating on an outer surface of said expandable portion, said amphiphilic polymer coating including;

an amphiphilic polymer or co-polymer complexed with iodine;

a hydrophobic therapeutic agent; and

a wax selected from the group consisting of bees wax, camauba wax, poly dimethyl siloxane, and polydimethyl siloxane derivatives.

10. The method of claim 9, wherein said amphiphilic polymer or co-polymer is selected from the group consisting of hydroxypropyl cellulose, poly (methyl vinyl ether-alt-maleic acid monobutyl ester), poly (methyl vinyl ether-alt-maleic acid monoethyl ester), and polyvinyl pyrrolidone.

11. The method of claim 9, wherein said wax is at a concentration of less than 1% by weight of said amphiphilic polymer or co-polymer complexed with iodine.

12. The method of claim 9, wherein said amphiphilic polymer coating further comprises a plasticizer selected from the group consisting of polyethylene glycol with a molecular weight below 10 K Daltons, propylene glycol, triethyl citrate, glycerol, and dibutyl sebacate.

13. The method of claim 12, wherein said plasticizer is at a concentration of less than 20% by weight of said amphiphilic polymer or co-polymer complexed with iodine.

14. The method of claim 9, wherein said hydrophobic therapeutic agent is selected from the group consisting of anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, thrombolytic agents, and combinations thereof.

15. The method of claim 9, wherein said hydrophobic therapeutic agent is selected from the group consisting of paclitaxel and dexamethasone acetate.

16. The method of claim 9, wherein forming said amphiphilic polymer coating comprises dip coating said medical disposable device in a coating solution utilizing a single dip.

17. The method of claim 9, wherein said amphiphilic polymer coating is substantially uniform over said outer surface, and said coating solution has a viscosity of 5 cps to 75 cps.

18. A method comprising:

applying a polymeric composition to at least a portion of an outer surface of an expandable portion of a disposable medical device, said polymeric composition including;

a hydrophobic therapeutic agent selected from the group consisting of anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, thrombolytic agents, and combinations thereof,

a plasticizer selected from the group consisting of polyethylene glycol with a molecular weight below 10 K Daltons, triethyl citrate, glycerol, and dibutyl sebacate, and

an amphiphilic polymer or co-polymer selected from the group consisting of hydroxypropyl cellulose, poly (methyl vinyl ether-alt-maleic acid monobutyl ester), poly (methyl vinyl ether-alt-maleic acid monoethyl ester), and polyvinyl pyrrolidone,

said amphiphilic polymer or co-polymer complexed with iodine,

wherein said polymeric composition is applied by dip coating.