Balloon catheter providing decreased irritation and improved drug release and drug penetration

• US 8,801,662 B2
• Filed: 05/21/2010
• Issued: 08/12/2014
• Est. Priority Date: 06/02/2009
• Status: Active Grant

• Current Assignee: Concept Medical Inc.
• Original Assignee: Concept Medical Inc.
• Inventors: Doshi, Manish, Sherdiwala, Divyesh, Sojitra, Prakash, Vyas, Ashwin, Gandhi, Pankaj
• Primary Examiner(s): VU, QUYNH-NHU HOANG
• Application Number:
  US12/920,812
• Publication Number:
  US 20120065584A1
• Time in Patent Office: 1,544 Days
• Field of Search: 604/103.02, 427/2.1, 427/2.3, 977/700, 977/906
• US Class Current: 604/103.02
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• 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: 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 2025/1088 having special surface characteristics depending on material properties or added substances, e.g. for reducing friction
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• 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 25/1027 Making of balloon catheters
• CPC Class Codes: A61M 25/104 used for angioplasty
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A drug-delivering medical device for delivering a drug to a target site in a body lumen is disclosed. The drug-delivering medical device includes a balloon catheter and an inflatable balloon positioned on the balloon catheter. The inflatable balloon has a hydrophilic surface. One or more portions of the hydrophilic surface are coated with two or more nano-carriers. A nano-carrier of the two or more nano-carriers includes a drug surrounded by an encapsulating medium. As the drug is surrounded by the encapsulating medium, the surface of the nano-carrier is devoid of the drug. When the inflatable balloon is inflated upon coming in proximity to a target site in the body lumen, about 30% to 80% of the two or more nano-carriers are released from the hydrophilic surface within 15-90 seconds.

Claims

1. A drug-delivering medical device for delivering agents to treat a target site via a blood vessel, comprising:

a balloon catheter; and

an inflatable balloon positioned on the balloon catheter,

the inflatable balloon having a hydrophilic surface,

at least one portion of the hydrophilic surface being coated with a plurality of nano-carriers, including;

a first set of nano-carriers comprising a pro-healing agent,

a second set of nano-carriers comprising an anti-proliferative agent, and a third set of nano-carriers comprising one or both of an anti-inflammatory agent and an anti-thrombogenic agent,

the first set of nano-carriers having a first average diameter ranging from 800 nm to 1500 nm suitable for penetrating an intima layer of a blood vessel through inter-tissue pores present in the intima layer,

the second set of nano-carriers having a second average diameter ranging from 300 nm to 800 nm suitable for penetrating a media layer of the blood vessel through a vasa vasorum associated with the media layer and the inter-tissue pores present in the intima layer, and

the third set of nano-carriers having a third diameter ranging from 10 nm to 300 nm suitable for penetrating an adventitia layer of the blood vessel through the inter-tissue pores present in the intima layer, the vasa vasorum associated with the media layer and a vasa vasorum associated with the adventitia layer;

wherein a first time required for the third set of nano-carriers to release from the hydrophilic surface upon coming in proximity of the target site is less than a second time required for the second set of nano-carriers and the first set of nano-carriers to release from the hydrophilic surface;

wherein the third set of nano-carriers exhibit a rapid rate of release from the hydrophilic surface and wherein the second set of nano-carriers and the first set of nano-carriers exhibit slower rates of release from the hydrophilic surface as compared with the rate of release of the third set of nano-carriers;

at least one adjacent portion of the hydrophilic surface being uncoated and exposable to a blood or a tissue environment for rapid dissolution from the inflatable balloon and for rapid dissolution from underneath the nano-carriers of an adjacent coated portion of the hydrophilic surface, the rapid dissolution from underneath providing an increase in the rapidity of release of the nano-carriers of the adjacent coated portion;

each nano-carrier of the plurality of nano-carriers comprising a respective agent surrounded by an encapsulating medium,

wherein a surface of each nano-carrier is devoid of the respective agent and 30% to 80% of the plurality of the nano-carriers are released from the hydrophilic surface within 15-90 seconds when the inflatable balloon is inflated upon coming in proximity to the target site in the blood vessel; and

wherein the third set of nano-carriers penetrating into the adventitia layer remain in the adventitia layer for a prolonged time and act as a reservoir of the one or both of the anti-inflammatory agent and the anti-thrombogenic agent to slowly release the one or both of the anti-inflammatory agent and the anti-thrombogenic over the prolonged time.

2. The drug-delivering medical device of claim 1, wherein the encapsulating medium comprises at least one of a biological agent, a phospholipid and a blood excipient.

3. The drug-delivering medical device of claim 1, wherein the inflatable balloon has a distal end and a proximal end and at least a portion of the distal end of the inflatable balloon and at least a portion of the proximal end of the inflatable balloon are not coated with the plurality of nano-carriers.

4. The drug-delivering medical device of claim 2, wherein the biological agent and the phospholipid have at least one effect selected from a group comprising affinity for the target site and stabilizing the drug.

5. The drug-delivering medical device of claim 2, wherein the biological agent dissolves in a medium having a pH less than 7.4.

6. The drug-delivering medical device of claim 2, wherein the at least one biological agent is selected from a group comprising drug carriers, excipients, blood components, excipients derived from blood, phospholipids, solid lipid nano-particles, lipoids, vitamins and sugar molecules.

7. The drug-delivering medical device of claim 2, wherein the biological agent is selected from a group comprising steroids, vitamins, estradiol, esterified fatty acids, non-estrified fatty acids, glucose, inositol, L-lactate, lipoproteins, carbohydrates, tricalcium phosphate, precipitated calcium phosphate, calcium phoshate tribasic, substances derived from at least one of human, egg and soybean, phospholipon 80H, phospholipon 90H, Lipoids S75, Lipoids E80, Intralipid 20, Lipoid EPC, Lipoids E75, lipids obtained from egg, lipids obtained from soya, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, phosphatidic acid, cardiolipin, and phosphatidylethanolamine.

8. The drug-delivering medical device of claim 1, wherein one of the agents is selected from a group comprising anti-proliferative agents, anti-inflammatory agents, anti-neoplastic agents, anti-coagulant agents, anti-fibrin agents, antithrombotic agents, anti-mitotic agents, antibiotic agents, anti-allergic agents and antioxidants, at least one flavonoid, estrogen, protease inhibitors, antibodies, immunosuppressive agents, cytostatic agents, cytotoxic agents, calcium channel blockers, phosphodiesterase inhibitors, prostaglandin inhibitors, dietary supplements, vitamins, anti-platelet aggregating agents and genetically engineered epithelial cells, wherein the at least one flavonoid is selected from a group comprising at least one of narigenin, naringin, eriodictyol, hesperetin, hesperidin (esperidine), kampferol, quercetin, rutin, cyanidol, meciadonol, catechin, epi-gallocatechin-gallate, taxifolin (dihydroquercetin), genistein, genistin, daidzein, biochanin, glycitein, chrysin, diosmin, luetolin, apigenin, tangeritin and nobiletin.

9. The drug-delivering medical device of claim 1, wherein one of the agents is selected from a group comprising sirolimus, paclitaxel, tacrolimus, clobetasol, dexamethasone, genistein, heparin, beta-estadiol, rapamycin, everolimus, ethylrapamycin, zotarolimus, ABT-578, Biolimus A9, docetaxel, methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride, mitomycin, sodium heparin, low molecular weight heparin, heparinoid, hirudin, argatroban, forskolin, vapiprost, prostacyclin, prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone, dipyridamole, glycoprotein IIb/IIIa, recombinant hirudin, bivalirudin, nifedipine, colchicines, lovastatin, nitroprusside, suramin, serotonin blockers, a steroid, thioprotease inhibitors, triazolopyrimidine, nitric oxide, nitric oxide donors, super oxide dismutase, super oxide dismutase mimetics, estradiol, aspirin, angiopeptin, captopril, cilazapril, lisinopril, permirolast potassium, alpha-interferon, and bioactive RGD.

10. The drug-delivering medical device of claim 1, wherein one of the agents is selected from a group comprising Sirolimus and Paclitaxel.

11. The drug-delivering medical device of claim 1, wherein the inflatable balloon is sized to contact an inner surface of the body lumen upon inflation.

12. The drug-delivering medical device of claim 1, wherein the drug-delivering medical device is used to treat a medical condition, wherein the medical condition is selected from of a group comprising stenosis, restenosis, blockages in an artery, thrombus in artery, acute myocardial infarction, and arterial lesions.