Drug releasing coatings for medical devices

• US 8,404,300 B2
• Filed: 03/07/2011
• Issued: 03/26/2013
• 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:
  US13/042,218
• Publication Number:
  US 20110159169A1
• Time in Patent Office: 750 Days
• Field of Search: None
• US Class Current: 427/2.25
• 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: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• 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 2300/428 Vitamins, e.g. tocopherol, riboflavin
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• 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 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 31/16 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 2210/1025 Respiratory system A61M2210/0618 take precedence
• 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: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

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. The additive has a hydrophilic part and a hydrophobic part and the therapeutic agent is not enclosed in micelles or encapsulated in particles or controlled release carriers.

Claims

1. A method for preparing a drug coated balloon catheter, the method comprising:

(a) preparing a solution comprising;

an organic solvent selected from the group consisting of hexane, octane, cyclohexane, heptane, benzene, toluene, xylene, methanol, ethanol, propanol, isopropanol, diethylamide, ethylene glycol monoethyl ether, Trascutol, benzyl alcohol, dioxane, dimethyl ether, tetrahydrofuran, ethyl acetate, isobutyl acetate, acetone, acetonitrile, diethyl ketone, methyl ethyl ketone, dimethylformamide, dimethylsulfoxide, mixtures of water and ethanol, mixtures of water and acetone, mixtures of water and methanol, mixtures of water and tetrahydrofuran, and combinations thereof;

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

at least one first additive selected from the group consisting of PEG sorbitan monolaurates, PEG sorbitan monooleates, and mixtures thereof; and

at least one additional additive selected from the group consisting of sorbitol, sorbitan, gluconolactone, and mixtures thereof;

(b) forming a coating layer containing the therapeutic agent and the at least one additive on an exterior surface of a balloon of a balloon catheter to form the drug coated balloon catheter by;

(i) applying the solution to the balloon in an inflated or partially inflated state; and

(ii) drying the balloon to evaporate the organic solvent from the coating solution after the solution is applied; and

(c) deflating and folding the balloon,

wherein the ratio by weight of the additives to the therapeutic agent in the coating layer is from 0.05 to 100.

2. The method according to claim 1, wherein the thickness of the coating layer is from about 0.1 μ

m to 200 μ

m.

3. The method according to claim 1, wherein the ratio by weight of the additives to the therapeutic agent in the coating layer is from 0.1 to 5.

4. The method according to claim 1, wherein the ratio by weight of the additives to the therapeutic agent in the coating layer is from 0.8 to 1.2.

5. The method according to claim 1, wherein the at least one additional additive is selected from the group consisting of sorbitol, sorbitan, and mixtures thereof.

6. The method according to claim 1, wherein the at least one first additive is selected from the group consisting of PEG-20 sorbitan monolaurate and PEG-20 sorbitan monooleate.

7. The method according to claim 1, wherein:

the at least one first additive is selected from the group consisting of PEG-20 sorbitan monolaurate and PEG-20 sorbitan monooleate; and

the at least one additional additive is selected from the group consisting of sorbitol, gluconolactone, and mixtures thereof.

8. The method according to claim 7, wherein the solution consists essentially of the organic solvent, the therapeutic agent, the at least one first additive, and the at least one additional additive.

9. The method according to claim 7, wherein the solution consists essentially of:

the organic solvent;

from 1% to 15% total by weight, based on the total weight of the solution, of the at least one first additive and the at least one additional additive; and

from 2% to 20% total by weight, based on the total weight of the solution, of the therapeutic agent, the at least first one additive, and the at least one additional additive.

10. The method according to claim 9, wherein the organic solvent is selected from the group consisting of ethanol;

mixtures of water and ethanol;

acetone;

mixtures of water and acetone;

mixtures of acetone and ethanol; and

mixtures of water, acetone, and ethanol.

11. The method according to claim 1, wherein (b)(i) and (b)(ii) are repeated until a therapeutically effective amount of the therapeutic agent in the coating layer is deposited on the exterior surface of the balloon.

12. The method according to claim 1, wherein (b)(i) and (b)(ii) are repeated until the exterior surface of the balloon has thereon a concentration density of therapeutic agent of from 1 μ

g/mm² to 20 μ

g/mm².

13. The method according to claim 1, wherein the solution comprises:

from 0.5% to 50% by weight, based on the total weight of the solution, of the therapeutic agent; and

from 1% to 45% by weight, based on the total weight of the solution, of the additives.

14. The method according to claim 1, wherein the solution comprises a total of from 2% to 20% by weight, based on the total weight of the solution, of the therapeutic agent and additives in the organic solvent.

15. The method according to claim 1, wherein the organic solvent is selected from the group consisting of methanol, ethanol, propanol, isopropanol, acetone, dioxane, tetrahydrofuran, dimethylformamide, acetonitrile, dimethylsulfoxide, and combinations thereof.

16. The method according to claim 1, wherein the organic solvent is selected from the group consisting of ethanol;

mixtures of water and ethanol;

acetone;

mixtures of water and acetone;

mixtures of acetone and ethanol; and

mixtures of water, acetone, and ethanol.