Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids

• US 8,414,526 B2
• Filed: 05/20/2008
• 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:
  US12/123,951
• Publication Number:
  US 20080255509A1
• Time in Patent Office: 1,785 Days
• Field of Search: None
• US Class Current: 604/103.02
• 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: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 29/08 Materials for coatings
• 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
• CPC Class Codes: A61M 2025/1031 Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
• 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 25/10 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 25/1029 Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
• CPC Class Codes: A61M 25/104 used for angioplasty

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, at least one of an oil, a fatty acid, and a lipid, 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, a part that has an affinity to the therapeutic agent by charge, and a part that has an affinity to the therapeutic agent by van der Waals interactions. In embodiments, the additive is at least one of a surfactant and a chemical compound. In further embodiments, the chemical compound is water-soluble.

Claims

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

a coating layer overlying an exterior surface of an inflatable balloon, the coating layer comprising;

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

at least one water-soluble first additive selected from the group consisting of PEG sorbitan fatty esters, gluconolactone, lactobionic acid, and combinations thereof; and

at least one water-insoluble second additive selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, dimyristoylphosphatidylcholine, and combinations thereof.

2. The balloon catheter of claim 1, wherein the at least one water-soluble first additive is selected from the group consisting of PEG sorbitan monolaurates, PEG sorbitan monooleates, gluconolactone, lactobionic acid, and combinations thereof.

3. The balloon catheter of claim 1, wherein the at least one water-soluble first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, gluconolactone, lactobionic acid, and combinations thereof.

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

5. The balloon catheter of claim 4, wherein the hydrophobic therapeutic agent is paclitaxel.

6. The balloon catheter of claim 1, wherein:

the at least one water-soluble first additive is gluconolactone.

7. The balloon catheter of claim 6, wherein the hydrophobic therapeutic agent is paclitaxel.

8. The balloon catheter of claim 1, wherein:

the at least one water-soluble first additive is lactobionic acid; and

the at least one water-insoluble second additive is phosphatidylcholine.

9. The balloon catheter of claim 8, wherein the hydrophobic therapeutic agent is paclitaxel.

10. The balloon catheter of claim 1, wherein:

the at least one water-soluble first additive is PEG-20 sorbitan monolaurate; and

the at least one water-insoluble second additive is phosphatidylcholine.

11. The balloon catheter of claim 10, wherein the hydrophobic therapeutic agent is paclitaxel.

12. The balloon catheter of claim 1, wherein the balloon catheter includes one of a perfusion balloon catheter, an infusion catheter, a perforated balloon, a porous balloon, a weeping balloon, a cutting balloon catheter, or a scoring balloon catheter.

13. The balloon catheter of claim 1, further comprising an adherent layer between the exterior surface of the balloon catheter and the coating layer, the adherent layer comprising at least one additive selected from the group consisting of PEG sorbitan fatty esters, gluconolactone, lactobionic acid, phosphatidylcholine, phosphatidylethanolamine, dimyristoylphosphatidylcholine, and combinations thereof.

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

15. The balloon catheter of claim 1, wherein the coating layer consists essentially of the hydrophobic therapeutic agent, the water-soluble first additive, and the water-insoluble second additive.

16. The balloon catheter of claim 1, wherein the coating layer further comprises sorbitol.

17. 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.

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

g/mm² to 6 μ

g/mm².

19. The balloon catheter of claim 1, wherein the total thickness of the coating layer is from 0.1 μ

m to 200 μ

m.

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

21. The balloon catheter of claim 1, wherein the ratio by weight of the therapeutic agent in the coating layer to the total weight of the first and second additives in the coating layer is from about 0.5 to 3.

22. 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 water-soluble 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.

23. The balloon catheter of claim 22, 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.

24. The balloon catheter of claim 23, wherein:

the hydrophobic therapeutic agent is paclitaxel; and

the top layer further comprises paclitaxel.

25. A balloon catheter for the delivery of a therapeutic agent to a target site of a blood vessel, the balloon catheter comprising:

a coating layer overlying an exterior surface of an inflatable balloon, the coating layer comprising;

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

at least one water-soluble first additive selected from the group consisting of PEG sorbitan fatty esters, gluconolactone, lactobionic acid, and combinations thereof; and

at least one water-insoluble second additive selected from the group consisting of soybean oil, vegetable oil, flower oil, coconut oil, palm oil, olive 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, and combinations thereof.

26. The balloon catheter of claim 25, wherein:

the hydrophobic therapeutic agent is paclitaxel;

the at least one water-soluble first additive is gluconolactone; and

the at least one water-insoluble second additive is selected from the group consisting of fish oil, soybean oil, and olive oil.

27. The balloon catheter of claim 25, wherein:

the hydrophobic therapeutic agent is paclitaxel;

the at least one water-soluble first additive is lactobionic acid; and

the at least one water-insoluble second additive is eicosapentaenoic acid.

28. The balloon catheter of claim 25, wherein:

the hydrophobic therapeutic agent is paclitaxel;

the at least one water-soluble first additive is PEG-20 sorbitan monolaurate; and

the at least one water-insoluble second additive is tocotrienol.