mTOR INHIBITOR ELUTING MEDICAL DEVICE

• US 20160151545A1
• Filed: 07/30/2014
• Published: 06/02/2016
• Est. Priority Date: 07/31/2013
• Status: Active Grant

• Current Assignee: Sahajanand Medical Technologies Pvt Ltd.
• Original Assignee: Sahajanand Medical Technologies Pvt Ltd.
• Inventors: RAVAL, ANKUR JAYKUMAR, ENGINEER, CHHAYA BABUBHAI, PATRAVALE, VANDANA BHARAT
• Granted Patent: US 10,639,403 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• 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 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/143 Stabilizers
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present disclosure relates to a coated implantable medical device, comprising: a base layer comprising mTOR inhibitor, and at least one biodegradable polymer; a middle layer comprising mTOR inhibitor, and at least one biodegradable polymer; and a top layer selected from the group consisting of hydrophilic polymer, and combination of hydrophilic polymer and antioxidant, wherein the total mTOR inhibitor concentration over the medical device is in the range of 0.7 to 3.00 μg/mm2. The present disclosure further relates to a method of preparing a coated implantable medical device.

Claims

1. A coated implantable medical device, comprising:

a base layer comprising mTOR inhibitor, and at least one biodegradable polymer;

a middle layer comprising mTOR inhibitor, and at least one biodegradable polymer; and

a top layer selected from the group consisting of hydrophilic polymer, and combination of hydrophilic polymer and antioxidant;

wherein the mTOR inhibitor concentration over the medical device is in the range of 0.7 to 3.00 μ

g/mm².

2. The coated implantable medical device as claimed in claim 1, wherein the middle layer and the base layer further comprises of an antioxidant.

3. The coated implantable medical device as claimed in claim 1, wherein the medical device is selected from the group consisting of a stent, a catheter balloon, guide wire, heart valve, catheter, vena cava filter, vascular graft, a stent graft and combinations thereof, preferably a stent.

4. The coated implantable medical device as claimed in claim 1, wherein the mTOR inhibitor is selected from the group consisting of everolimus, pimecrolimus, tacrolimus, zotarolimus, biolimus, rapamycin and combinations thereof, preferably everolimus.

5. The coated implantable medical device as claimed in claim 1, wherein the at least one biodegradable polymer is selected from the group consisting of poly L-Lactide-caprolactone (PLCL), poly L-Lactide (PLLA), poly dl lactide (PDLLA), poly dl lactide-co-glycolide (PLGA), poly di lactide-co-caprolactone (PLLCL), and combinations thereof, preferably poly L-Lactide-caprolactone (PLCL), poly L-Lactide (PLLA) and combinations thereof.

6. The coated implantable medical device as claimed in claim 1, wherein the antioxidant is selected from the group consisting of tocopherol acetate, Vitamin E, butylated hydroxyl toluene (BHT) and combinations thereof, preferably tocopherol acetate.

7. The coated implantable medical device as claimed in claim 1, wherein the hydrophilic polymer is selected from the group consisting of pyrrolidones, poly ethylene glycols and combinations thereof, preferably polyvinyl pyrrolidone.

8. The coated implantable medical device as claimed in claim 1, wherein the at least one biodegradable polymer in the base layer and middle layer has a weight ratio in the range from 10% to 40% based on the mTOR inhibitor weight.

9. The coated implantable medical device as claimed in claim 1, wherein the mTOR inhibitor to the at least one biodegradable polymer in the base layer has a weight ratio in the range of 10:

90 to 30;

70 by weight, preferably in the range of 10;

90 to 35;

65 by weight, most preferably in 15;

85 by weight.

10. The coated implantable medical device as claimed in claim 1, wherein the mTOR inhibitor to the at least one biodegradable polymer in the middle layer has a weight ratio in the range of 15:

85 to 40;

60 by weight, preferably in the range of 15;

85 to 35;

65 by weight, most preferably in 25;

75 by weight.

11. The coated implantable medical device as claimed in claim 1, comprising:

a base layer comprising everolimus and a blend of poly L-Lactide-caprolactone (PLCL), poly L-Lactide (PLLA);

a middle layer comprising everolimus and a blend of poly L-Lactide-caprolactone (PLCL), poly L-Lactide (PLLA); and

a top layer comprising polyvinyl pyrrolidone and tocopherol acetate,

wherein the total mTOR inhibitor concentration over the medical device is in the range of 0.7 to 3.00 μ

g/mm².

12. A method of preparing a coated implantable medical device as claimed in claim 1, the process comprising:

pre-cleaning the medical device using an organic solvent to obtain a cleaned medical device; and

coating the cleaned medical device with a base layer comprising mTOR inhibitor, and at least one biodegradable polymer;

a middle layer comprising mTOR inhibitor, and at least one biodegradable polymer; and

a top layer selected from the group consisting of hydrophilic polymer, and combination of hydrophilic polymer and antioxidant to obtain a coated implantable medical device;

wherein the mTOR inhibitor and the polymer in the base layer and the middle layer has a solution concentration in the range of 0.01 to 1% (w/v).

13. The method as claimed in claim 12, wherein the polymer and the antioxidant in the top layer has a solution concentration in the range of 0.01 to 5% (w/v).

14. The method as claimed in claim 12, wherein the organic solvent is selected from the group consisting of dichloromethane, chloroform, hexafluoro isopropanol, and combinations thereof.

15. The coated implantable medical device as claimed in claim 12, wherein the coating process is done on the abluminal surface, luminal surface and side walls.

16. The coated implantable medical device as claimed in claim 1, wherein the device is a stent.

17. The coated implantable medical device as claimed in claim 16, wherein the mTOR inhibitor is everolimus.

18. The coated implantable medical device as claimed in claim 17, wherein the at least one biodegradable polymer is poly L-Lactide (PLLA) and/or poly L-Lactide-caprolactone (PLCL).

19. The coated implantable medical device as claimed in claim 18, wherein the antioxidant is tocopheral acetate.

20. The coated implantable medical device as claimed in claim 19, wherein the hydrophilic polymer is polyvinyl pyrrolidone.