DRUG RELEASING COATINGS FOR MEDICAL DEVICES

• US 20110159169A1
• Filed: 03/07/2011
• Published: 06/30/2011
• 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
• Granted Patent: US 8,404,300 B2
• Time in Patent Office: Days
• 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

1-160. -160. (canceled)

161. A method for preparing a medical device, the method comprising:

(a) preparing a solution comprising an organic solvent, a therapeutic agent, and at least one additive, wherein a single additive of the at least one additive comprises a hydrophilic part and a hydrophobic part, and wherein the therapeutic agent is not enclosed in micelles or encapsulated in polymer particles, and wherein the solution does not include an iodine covalent bonded contrast agent, oil, or a lipid;

(b) applying the solution to a medical device; and

(c) drying the solution, forming a layer,

wherein the ratio by weight of the at least one additive to the therapeutic agent in the layer is from about 0.05 to 100.

162. The method according to claim 161, wherein the solution is applied by dipping a portion of the medical device in the solution.

163. The method according to claim 161, wherein the solution is applied by spraying the medical device with the solution.

164. The method according to claim 161, wherein steps (b) and (c) are repeated until a therapeutically effective amount of the therapeutic agent in the layer is deposited on a surface of the medical device.

165. The method according to claim 161, wherein the thickness of the layer is from about 0.1 to 200 microns.

166. The method according to claim 161, further comprising applying a dimethylsulfoxide solvent to the layer obtained after said drying in step (c).

167. The method according to claim 161, wherein the ratio by weight of the additive to the therapeutic agent in the layer is 0.1 to 5.

168. The method according to claim 161, wherein the medical device is chosen from a balloon catheter, a stent, a guide catheter, a guide wire, an embolic protection device, and an imaging device.

169. The method according to claim 161, wherein the therapeutic agent comprises one of paclitaxel, a paclitaxel analogue, rapamycin, a rapamycin analogue, beta-lapachone, a beta-lapachone analogue, biological vitamin D, a biological vitamin D analogue, and a mixture of two or more of these therapeutic agents.

170. The method according to claim 161, wherein the additive comprises one or more substances selected from a group consisting of alcohols and PEG fatty esters.

171. The method according to claim 170, wherein the PEG fatty esters consist of one or more of Tween 20, Tween 40, Tween 60, Tween 80, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG sorbitan laurate, PEG sorbitan oleate, and PEG sorbitan palmitate.

172. The method according to claim 170, wherein the alcohol consist of one or more of amino alcohols, polyalcohols, polyglycidols, glycerol, multiglycerols, ethyl glycol, sorbitol, sorbitan, and pentaerythritol.

173. The method according to claim 161, wherein the hydrophilic part of the at least one additive comprises a hydroxyl, carboxyl, carbonyl, ester, ether, amide, or amine group, or carboxylic acid, anhydride, ethyl oxide, ethyl glycol, polyethylene glycol, ascorbic acid, amino acid, amino alcohol, glucose, sucrose, sorbitan, glycerol, polyalcohol, phosphate, sulfate, or an organic salt.

174. The method according to claim 161, wherein the at least one additive comprises a surfactant and has a fatty chain of an acid, ester, ether, or alcohol.

175. The method according to claim 161, wherein the at least one additive comprises a non-ionic surfactant having a hydrophilic-lipophilic balance value of greater than about 4.

176. The method according to claim 161, wherein the at least one additive comprises an ionic or non-ionic surfactant.

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

(a) preparing a solution comprising an organic solvent, a therapeutic agent, and at least one additive, wherein the solution does not include an iodine covalent bonded contrast agent, oil, or a lipid, and

(b) forming a layer on a balloon of the balloon catheter by;

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

(ii) drying the balloon; and

(iii) deflating and folding the balloon,

wherein the ratio by weight of the at least one additive to the therapeutic agent in the layer is 0.05 to 100.

178. The method according to claim 177, wherein the therapeutic agent comprises one of paclitaxel, a paclitaxel analogue, rapamycin, a rapamycin analogue, beta-lapachone, a beta-lapachone analogue, biological vitamin D, a biological vitamin D analogue, and a mixture of two or more of these therapeutic agents.

179. The method according to claim 177, wherein the additive comprises one or more substances selected from a group consisting of alcohols and PEG fatty esters.

180. The method according to claim 179, wherein the PEG fatty esters consist of one or more of Tween 20, Tween 40, Tween 60, Tween 80, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG sorbitan laurate, PEG sorbitan oleate, and PEG sorbitan palmitate.

181. The method according to claim 179, wherein the alcohols consist of one or more of amino alcohols, polyalcohols, polyglycidols, glycerol, multiglycerols, ethyl glycol, sorbitol, sorbitan, and pentaerythritol.

182. The method according to claim 177, wherein a single additive of the at least one additive comprises a hydrophilic part and a hydrophobic part, and wherein the hydrophilic part of the at least one additive comprises one or more of a hydroxyl, carboxyl, carbonyl, ester, ether, amide, or amine group, or carboxylic acid, anhydride, ethyl oxide, ethyl glycol, polyethylene glycol, ascorbic acid, amino acid, amino alcohol, glucose, sucrose, sorbitan, glycerol, polyalcohol, phosphate, sulfate, or an organic salt.

183. The method according to claim 177, wherein the at least one additive comprises a surfactant and has a fatty chain of an acid, ester, ether, or alcohol.

184. The method according to claim 177, wherein the at least one additive comprises a non-ionic surfactant having a hydrophilic-lipophilic balance value of greater than about 10.

185. The method according to claim 177, wherein the at least one additive comprises an ionic or non-ionic surfactant.

186. The method according to claim 177, wherein the at least one additive comprises one or more of albumin, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidinone, polypeptides, water-soluble surfactants, water-soluble vitamins, and proteins.

187. The method according to claim 177, wherein the thickness of the coating layer is from about 0.1 to 200 microns.

188. The method according to claim 177, wherein the ratio by weight of the at least one additive to the therapeutic agent in the coating layer is 0.1 to 5.

189. The method according to claim 177, wherein the ratio by weight of the at least one additive to the therapeutic agent in the coating layer is 0.8 to 1.2.