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

• US 8,128,951 B2
• Filed: 02/24/2010
• Issued: 03/06/2012
• Est. Priority Date: 09/15/2008
• Status: Active Grant

• Current Assignee: Spectranetics Corporation (Koninklijke Philips N.V.)
• Original Assignee: Cv Ingenuity Corp. (Medtronic Plc)
• Inventors: Michal, Eugene T., Lerner, Daniel J., Pollman, Matthew J.
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US12/712,134
• Publication Number:
  US 20100198190A1
• Time in Patent Office: 741 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61L 2300/106 Halogens or compounds thereof, e.g. iodine, chlorite
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/10 Inorganic materials
• CPC Class Codes: A61L 29/141 Plasticizers
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/128 containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A method and device for local delivery of water-soluble or water-insoluble therapeutic agents to the tissue 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 a non-durable coating which is complexed with iodine and has a substantially water-insoluble therapeutic agent dispersed therein. The medical disposable device is inserted into a body lumen, and expanded to contact the non-durable coating against the body lumen and deliver the substantially water-insoluble therapeutic agent to the body lumen tissue.

Claims

1. A catheter assembly for insertion into the vasculature comprising:

an expandable structure having an outer surface;

a non-durable coating disposed on the outer surface of the expandable structure, wherein the non-durable coating comprises a polymer matrix which is complexed with iodine; and

a substantially water-insoluble therapeutic agent dispersed in the matrix which is complexed with the iodine.

2. The catheter assembly of claim 1, wherein the polymer matrix is a continuous aggregate polymer matrix which is uniformly dissolvable and removable from the outer surface of the expandable structure in an aqueous solvent, and at least partially dissolvable in a non-aqueous solvent.

3. The catheter assembly of claim 2, wherein the continuous aggregate polymer matrix comprises an amphiphilic polymer or co-polymer which is fully dissolvable in a solution having a range of 100% to 80% non-aqueous solvent, and 0% to 20% aqueous solvent.

4. The catheter assembly of claim 1, wherein said non-durable coating is dissolvable in bovine serum such that 50%, by volume, of said non-durable coating is removed within 180 seconds of soaking in bovine serum at 37°

C.

5. The catheter assembly of claim 4, wherein said non-durable coating is dissolvable in bovine serum such that 90%, by volume, of said non-durable coating is removed within 300 seconds of soaking in bovine serum at 37°

C.

6. The catheter assembly of claim 1, wherein said iodine is complexed with polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP) or hydroxypropyl cellulose (HPC).

7. The catheter assembly of claim 1, wherein said water-insoluble therapeutic agent is paclitaxel.

8. The catheter assembly of claim 2, wherein the continuous aggregate polymer matrix is uniformly dissolvable and removable from the outer surface in both aqueous solvent and non-aqueous solvent.

9. A catheter assembly of claim 1, wherein said iodine is present in said coating at a weight ratio of 1-30% of said coating dry weight.

10. The catheter assembly of claim 1, wherein said iodine is complexed with methyl cellulose, hydroxypropyl methylcellulose, or a co-polymer of N-vinylpyrrolidone with a reactive double bond containing monomer.

11. The catheter assembly of claim 10, wherein the reactive double bond containing monomer is selected from the group consisting of styrene, acrylic acid, vinyl acetate and vinyl caprolactam.

12. The catheter assembly of claim 1, wherein the substantially water-insoluble therapeutic agent is dispersed throughout the polymer matrix which is complexed with the iodine.

21. The catheter assembly of claim 1, wherein the polymer matrix comprises polyethylene glycol (PEG).

22. The catheter assembly of claim 21, wherein the PEG has a molecular weight of 1.5 KD to 50 KD.

13. A catheter assembly for insertion into the vasculature comprising:

an expandable structure having an outer surface;

a non-durable coating disposed on the outer surface of the expandable structure, wherein the non-durable coating comprises a polymer matrix; and

a substantially water-insoluble therapeutic agent and non-covalently bound iodine dispersed throughout the polymer matrix.

14. The catheter assembly of claim 13, wherein the polymer matrix is a continuous aggregate polymer matrix which is dissolvable and removable from the outer surface of the expandable structure in an aqueous solvent, and at least partially dissolvable in a non-aqueous solvent.

15. The catheter assembly of claim 14, wherein the continuous aggregate polymer matrix comprises an amphiphilic polymer or co-polymer which is fully dissolvable in a solution having a range of 100% to 80% non-aqueous solvent, and 0% to 20% aqueous solvent.

16. The catheter assembly of claim 13, wherein the polymer matrix comprises a polymer selected from the group consisting of polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP) and hydroxypropyl cellulose (HPC).

17. The catheter assembly of claim 13, wherein the water-insoluble therapeutic agent is paclitaxel.

18. A catheter assembly of claim 13, wherein the iodine is present in the coating at a weight ratio of 1-30% of said coating dry weight.

19. The catheter assembly of claim 13, wherein the polymer matrix comprises a polymer selected from the group consisting of methyl cellulose and hydroxypropyl methylcellulose, or a co-polymer of N-vinylpyrrolidone with a reactive double bond containing monomer.

20. The catheter assembly of claim 19, wherein the reactive double bond containing monomer is selected from the group consisting of styrene, acrylic acid, vinyl acetate and vinyl caprolactam.

23. The catheter assembly of claim 13, wherein the polymer matrix comprises polyethylene glycol (PEG).

24. The catheter assembly of claim 23, wherein the PEG has a molecular weight of 1.5 KD to 50 KD.