Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent

• US 8,425,459 B2
• Filed: 05/20/2008
• Issued: 04/23/2013
• 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:
  US12/123,956
• Publication Number:
  US 20080255510A1
• Time in Patent Office: 1,799 Days
• Field of Search: None
• US Class Current: 604/103.02
• CPC Class Codes: A61B 17/320725 with radially expandable cutting or abrading elements A61B17/32075 takes precedence
• CPC Class Codes: A61B 18/24 with a catheter A61B18/26, A61B18/28 take precedence
• CPC Class Codes: A61B 18/245 for removing obstructions in blood vessels or calculi
• CPC Class Codes: A61B 2018/00327 Ear, nose or throat
• CPC Class Codes: A61B 2018/00345 Vascular system
• CPC Class Codes: A61B 2018/00446 Brain
• CPC Class Codes: A61B 2018/00488 Esophagus
• CPC Class Codes: A61B 2018/00505 Urinary tract
• CPC Class Codes: A61F 2/07 Stent-grafts
• 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: 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 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 29/08 Materials for coatings
• 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 29/18 : Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61L 31/08 : Materials for coatings
• 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: A61L 31/18 : Materials at least partially X-ray or laser opaque
• 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 25/09 : Guide wires
• 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 25/1002 : characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61M 31/005 : for contrast media
• CPC Class Codes: A61M 37/00 : Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 5/007 : for contrast media

Abstract

The invention relates to a coated medical device for rapid delivery of a therapeutic agent to a tissue in seconds to minutes. The medical device has a layer overlying the exterior surface of the medical device. The layer contains a therapeutic agent, a contrast agent, and an additive.

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, a contrast 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 contrast agent is selected from the group consisting of iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, and ioxaglate; 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.

2. 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.

3. The balloon catheter of claim 1, wherein the contrast agent is selected from the group consisting of iopromide, ioversol, and iomeprol.

4. The balloon catheter of claim 1, wherein:

the contrast agent is selected from the group consisting of iopromide, ioversol, and iomeprol; and

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.

5. The balloon catheter of claim 4, wherein:

the therapeutic agent is paclitaxel;

the contrast agent is iopromide; and

the at least one first additive is PEG-20 sorbitan monolaurate.

6. The balloon catheter of claim 4, wherein:

the therapeutic agent is paclitaxel;

the contrast agent is iopromide; and

the at least one first additive is PEG-20 sorbitan monopalmitate.

7. The balloon catheter of claim 4, wherein:

the therapeutic agent is rapamycin;

the contrast agent is iopromide; and

the at least one first additive is PEG-20 sorbitan monolaurate.

8. The balloon catheter of claim 4, wherein:

the therapeutic agent is rapamycin;

the contrast agent is iopromide; and

the at least one first additive is PEG-20 sorbitan monopalmitate.

9. The balloon catheter of claim 4, wherein:

the therapeutic agent is paclitaxel;

the contrast agent is ioversol; and

the at least one first additive is PEG-20 sorbitan monolaurate.

10. The balloon catheter of claim 4, wherein:

the therapeutic agent is paclitaxel;

the contrast agent is ioversol; and

the at least one first additive is PEG-20 sorbitan monopalmitate.

11. The balloon catheter of claim 4, wherein:

the therapeutic agent is rapamycin;

the contrast agent is iomeprol; and

the at least one first additive is PEG-20 sorbitan monolaurate.

12. The balloon catheter of claim 4, wherein:

the therapeutic agent is rapamycin;

the contrast agent is iomeprol; and

the at least one first additive is PEG-20 sorbitan monopalmitate.

13. The balloon catheter of claim 1, wherein the coating layer further comprises a hydrophilic second additive selected from the group consisting of polyglyceryl-10 oleate, p-isononylphenoxypolyglycidol, L-ascorbic acid, D-glucoascorbic acid, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, glucoheptonic acid, glucomic acid, hydroxyl ketone, hydroxyl lactone, 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, gentisic acid, lactobionic acid, lactitol, sorbitol, glucose, ribose, arabinose, lyxose, xylose, fructose, mannose, glucitol, glucopyranose phosphate, sinapic acid, vanillic acid, vanillin, methyl paraben, propyl paraben, diethylene glycol, triethylene glycol, tetraethylene glycol, xylitol, 2-ethoxyethanol, galactose, glucose, mannose, xylose, sucrose, lactose, maltose, cyclodextrin, sorbitol, (2-hydroxypropyl)-cyclodextrin, acetaminophen, ibuprofen, retinoic acid, lysine acetate, gentisic acid, catechin, catechin gallate, tiletamine, ketamine, propofol, lactic acids, acetic acid, and salts of any of the foregoing organic acids or amines.

14. The balloon catheter of claim 13, wherein the hydrophilic second additive is selected from the group consisting of polyglyceryl-10 oleate, p-isononylphenoxypolyglycidol, gluconolactone, sorbitol, lactobionic acid, and N-octanoyl-N-methylglucamine.

15. The balloon catheter of claim 13, wherein the hydrophilic second additive is selected from the group consisting of gluconolactone, sorbitol, lactobionic acid, N-octanoyl-N-methylglucamine, and combinations thereof.

16. The balloon catheter of claim 13, wherein the hydrophilic second additive is selected from the group consisting of gluconolactone, sorbitol, and combinations thereof.

17. The balloon catheter of claim 13, wherein the at least one first additive is PEG-20 sorbitan monolaurate and the hydrophilic second additive is selected from the group consisting of gluconolactone, sorbitol, lactobionic acid, N-octanoyl-N-methylglucamine, and combinations thereof.

18. The balloon catheter of claim 13, wherein the at least one first additive is PEG-20 sorbitan monolaurate, and the hydrophilic second additive is selected from the group consisting of gluconolactone, sorbitol and combinations thereof.

19. The balloon catheter of claim 13, wherein the therapeutic agent is paclitaxel, the at least one first additive is PEG-20 sorbitan monolaurate, and the hydrophilic second additive is selected from the group consisting of gluconolactone, sorbitol, and combinations thereof.

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

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

22. The balloon catheter of claim 1, wherein the coating layer further comprises a hydrophobic second additive selected from the group consisting of soybean oil, vegetable oil, flower oil, animal oil, coconut oil, palm oil, olive oil, peanut oil, fish oil, butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienol, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, monoacylglycerols, diacylglycerols, triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, alpha tocoferol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamines phosphatidylglycerols, sphingolipids, prostaglandins, gangliosides, neobee, and niosomes.

23. The balloon catheter of claim 22, wherein the hydrophobic second additive is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, and dimyristoylphosphatidylcholine.

24. 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.

25. The balloon catheter of claim 1, wherein the coating layer consists essentially of the therapeutic agent, the contrast agent, and the at least one first additive.

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

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

g/mm² to 20 μ

g/mm².

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

g/mm² to 10 μ

g/mm².

29. 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.

30. 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.

31. 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.

32. The balloon catheter of claim 1, wherein the coating layer does not include an oil or lipid.

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

34. The balloon catheter of claim 1, wherein the coating layer does not include a polymer.

35. The balloon catheter of claim 1, wherein the balloon catheter is a perfusion balloon catheter, a cutting balloon catheter, or a scoring balloon catheter.

36. The balloon catheter of claim 1, further comprising a top layer overlying the surface of the coating layer, wherein the top layer comprises a top-layer additive selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 monostearate, PEG-20 sorbitan monooleate, polyglyceryl oleate, polyethylene oxide, polyethylene glycol, polyvinyl pyrrolidone, 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.

37. The balloon catheter of claim 36, wherein the top-layer additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 monostearate, PEG-20 sorbitan monooleate, polyglyceryl oleate, polyethylene oxide, polyethylene glycol, and polyvinyl pyrrolidone.

38. The balloon catheter of claim 37, wherein the top layer further comprises a therapeutic agent selected from the group consisting of paclitaxel, rapamycin, and combinations thereof.

39. The balloon catheter of claim 38, wherein the concentration of the therapeutic agent in the top layer is lower than the concentration of the therapeutic agent in the coating layer.