Drug releasing coatings for medical devices

• US 8,414,525 B2
• Filed: 05/16/2008
• Issued: 04/09/2013
• Est. Priority Date: 11/20/2006
• Status: Active Grant

• Current Assignee: Lutonix, Inc. (Becton, Dickinson & Co)
• Original Assignee: Lutonix, Inc. (Becton, Dickinson & Co)
• Inventors: Wang, Lixiao
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US12/121,986
• Publication Number:
  US 20080255508A1
• Time in Patent Office: 1,789 Days
• Field of Search: None
• US Class Current: 604/103.02
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/80 characterised by a special chemical form
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The invention relates to a medical device for delivering a therapeutic agent to a tissue. The medical device has a layer overlying the exterior surface of the medical device. The layer contains a therapeutic agent and an additive. In certain embodiments, the additive has a hydrophilic part and a drug affinity part, wherein the drug affinity part is at least one of a hydrophobic part, a part that has an affinity to the therapeutic agent by hydrogen bonding, and a part that has an affinity to the therapeutic agent by van der Waals interactions. In embodiments, the additive is water-soluble. In further embodiments, the additive is at least one of a surfactant and a chemical compound, and the chemical compound has a molecular weight of from 80 to 750 or has more than four hydroxyl groups.

Claims

1. A balloon catheter for delivering a therapeutic agent to target site in a blood vessel, the balloon catheter comprising:

a coating layer overlying an exterior surface of a balloon, the coating layer comprising a therapeutic agent and at least one first additive, wherein;

the therapeutic agent is selected from the group consisting of paclitaxel, rapamycin, and combinations thereof; and

the at least one first additive comprises a PEG fatty ester selected from the group consisting of PEG laurates, PEG oleates, PEG stearates, PEG glyceryl laurates, PEG glyceryl oleates, PEG glyceryl stearates, PEG sorbitan monolaurates, PEG sorbitan monooleates, PEG sorbitan stearates, PEG sorbitan laurates, PEG sorbitan oleates, PEG sorbitan palmitates, and combinations thereof; and

an adherent layer between the coating layer and the exterior surface of the balloon, the adherent layer comprising a biocompatible polymer selected from the group consisting of polyolefins, polyisobutylene, ethylene-1-olefin copolymers, acrylic polymers, polyvinyl chloride, polyvinyl methyl ether, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polystyrene, polyvinyl acetate, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, Nylon 12, polycaprolactone, epoxy resins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, chitins, polylactic acid, polyglycolic acid, polylactic acid-polyethylene oxide copolymers, silicones, ethylene vinyl acetate copolymers, EPDM rubbers, and mixtures and block copolymers thereof.

2. The balloon catheter of claim 1, wherein the adherent layer does not contain a therapeutic agent.

3. The balloon catheter of claim 1, wherein the at least one first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 sorbitan monostearate, PEG-20 sorbitan monooleate, and combinations thereof.

4. The balloon catheter of claim 1, wherein the at least one first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monooleate, and combinations thereof.

5. The balloon catheter of claim 1, wherein the coating layer further comprises a second additive selected from the group consisting of polyglyceryl-10 oleate, octoxynol-9, p-isononylphenoxypolyglycidol, Tyloxapol, niacinamide, nicotinic acid, thiamine hydrochloride, 2-pyrrolidone-5-carboxylic acid, gluconolactone, sorbitol, meglumine, lactobionic acid, N-octanoyl-N-methylglucamine, lactic acid, gensitic acid, diethanolamine, and combinations thereof.

6. The balloon catheter of claim 5, wherein the second additive is selected from the group consisting of polyglyceryl-10 oleate, p-isononylphenoxypolyglycidol, gluconolactone, sorbitol, lactobionic acid, N-octanoyl-N-methylglucamine, and combinations thereof.

7. The balloon catheter of claim 5, wherein the second additive is selected from the group consisting of gluconolactone, sorbitol, lactobionic acid, N-octanoyl-N-methylglucamine, and combinations thereof.

8. The balloon catheter of claim 5, wherein the second additive is selected from the group consisting of gluconolactone, sorbitol, and combinations thereof.

9. The balloon catheter of claim 5, wherein the at least one first additive is PEG-20 sorbitan monolaurate and the second additive is selected from the group consisting of gluconolactone, sorbitol, lactobionic acid, N-octanoyl-N-methylglucamine, and combinations thereof.

10. The balloon catheter of claim 5, wherein the at least one first additive is PEG-20 sorbitan monolaurate, and the second additive is selected from the group consisting of gluconolactone, sorbitol and combinations thereof.

11. The balloon catheter of claim 5, wherein the therapeutic agent is paclitaxel, the at least one first additive is PEG-20 sorbitan monolaurate, and the second additive is selected from the group consisting of gluconolactone, sorbitol, and combinations thereof.

12. The balloon catheter of claim 5, wherein the therapeutic agent is paclitaxel, the at least one first additive is PEG-20 sorbitan monolaurate, and the second additive is gluconolactone.

13. The balloon catheter of claim 5, wherein the therapeutic agent is paclitaxel, the at least one first additive is PEG-20 sorbitan monolaurate, and the second additive is sorbitol.

14. The balloon catheter of claim 1, wherein the catheter further comprises a dimethylsulfoxide solvent layer overlying the surface of the coating layer.

15. The balloon catheter of claim 1, wherein the coating layer further comprises a second therapeutic agent selected from the group consisting of beta-lapachone and biologically active vitamin D.

16. The balloon catheter of claim 1, wherein the concentration of the therapeutic agent in the coating layer is from 1 to 20 μ

g/mm².

17. The balloon catheter of claim 1, wherein the concentration of the therapeutic agent in the coating layer is from 2 to 10 μ

g/mm².

18. The balloon catheter of claim 1, wherein the ratio by weight of the at least one first additive to the therapeutic agent in the coating layer is from about 0.1 to 5.

19. The balloon catheter of claim 1, wherein the ratio by weight of the at least one first additive to the therapeutic agent in the coating layer is from about 0.5 to 2.

20. The balloon catheter of claim 1, wherein the ratio by weight of the at least one first additive to the therapeutic agent in the coating layer is from about 0.8 to 1.2.

21. The balloon catheter of claim 1, wherein the coating layer does not include an iodine covalent bonded contrast agent.

22. The balloon catheter of claim 1, wherein the at least one first additive is not a therapeutic agent.

23. The balloon catheter of claim 1, wherein the at least one first additive is not salicylic acid or salts thereof.

24. The balloon catheter of claim 1, wherein the coating layer does not include oil.

25. The balloon catheter of claim 1, wherein the therapeutic agent is not enclosed in micelles or encapsulated in polymer particles.

26. The balloon catheter of claim 25, wherein the coating layer does not include a polymer.

27. The balloon catheter of claim 1, further comprising a top layer overlying the surface of the coating layer, wherein the top layer comprises an additive that is less hydrophilic than the at least one first additive in the coating layer, and wherein the additive in the top layer is selected from the group consisting of p-isononylphenoxypolyglycidol, PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 monostearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG oleyl ether, PEG lauryl ether, octoxynol, monoxynol, tyloxapol, sucrose monopalmitate, sucrose monolaurate, decanoyl-N-methylglucamide, n-decyl-β

-D-glucopyranoside, n-decyl-β

-D-maltopyranoside, n-dodecyl-β

-D-glucopyranoside, n-dodecyl-β

-D-maltoside, heptanoyl-N-methylglucamide, n-heptyl-β

-D-glucopyranoside, n-heptyl-β

-D-thioglucoside, n-hexyl-β

-D-glucopyranoside, nonanoyl-N-methylglucamide, n-nonyl-β

-D-glucopyranoside, octanoyl-N-methylglucamide, n-octyl-β

-D-glucopyranoside, octyl-β

-D-thioglucopyranoside, cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, methionine, ascorbic acid, 2-pyrrolidone-5-carboxylic acid, sodium pyrrolidone carboxylate, ethylenediaminetetraacetic dianhydride, cetotiamine;

cyclothiamine, dexpanthenol, niacinamide, nicotinic acid, pyridoxal 5-phosphate, nicotinamide ascorbate, riboflavin, riboflavin phosphate, thiamine, folic acid, menadiol diphosphate, menadione sodium bisulfite, menadoxime, vitamin B12, vitamin K5, vitamin K6, vitamin U, albumin, benzalkonium chloride, benzethonium chloride, docecyl trimethyl ammonium bromide, sodium dodecylsulfates, dialkyl methylbenzyl ammonium chloride, dialkylesters of sodium sulfonsuccinic acid, L-ascorbic acid and its salts, D-glucoascorbic acid and its salts, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, amine alcohols, glucoheptonic acid, gluconic acid, hydroxy ketones, hydroxy lactones, gluconolactone, glucoheptonolactone, glucooctanoic lactone, gulonic acid lactone, mannoic lactone, ribonic acid lactone, lactobionic acid, glucosamine, glutamic acid, benzyl alcohol, benzoic acid, hydroxybenzoic acid, propyl 4-hydroxybenzoate, lysine acetate salt, gentisic acid, lactitol, sinapic acid, vanillic acid, vanillin, methyl paraben, propyl paraben, sorbitol, cyclodextrin, (2-hydroxypropyl)-cyclodextrin, acetaminophen, ibuprofen, retinoic acid, lysine acetate, gentisic acid, catechin, catechin gallate, tiletamine, ketamine, propofol, and combinations thereof.

28. The balloon catheter of claim 27, wherein the additive in the top layer is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 monostearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, and polyglyceryl-10 palmitate.

29. The balloon catheter of claim 27, wherein the top layer further comprises a therapeutic agent selected from the group consisting of paclitaxel, rapamycin, or combinations thereof.

30. The balloon catheter of claim 29, wherein the concentration of the therapeutic agent in the top layer is lower than the concentration of the therapeutic agent in the coating layer.