mTOR inhibitor eluting medical device
Inventors
RAVAL, ANKUR JAYKUMAR • ENGINEER, CHHAYA BABUBHAI • Patravale, Vandana Bharat
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10639403-B2
Publication Date
2020-05-05
Expiration Date
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.
Core Innovation
The invention relates to a coated implantable medical device selected from the group consisting of a stent, a guide wire, a heart valve, a catheter, a vena cava filter, a vascular graft, a stent graft and combinations thereof. The device includes a three-layer coating having a base layer, a middle layer, and a top layer, where the base layer and the middle layer each include one or more mTOR inhibitors dispersed in one or more biodegradable polymers, optionally with one or more antioxidants.
The base layer and the middle layer provide different mTOR inhibitor distributions, including a defined weight ratio of one or more mTOR inhibitors to one or more biodegradable polymers and a requirement that the weight ratio in the middle layer is greater than in the base layer. The top layer is mTOR inhibitor-free and is selected from one or more hydrophilic polymers, and combinations of one or more hydrophilic polymers with one or more antioxidants.
The coating defines a total mTOR inhibitor concentration over the medical device in a range of from 0.7 to 3.00 μg/mm2 and a release profile in which from 10 to 30% of the total amount of the one or more mTOR inhibitors is released in the first 24 hours after use, with the remainder being released over a period of time of 28 days or longer. The base and middle layers use biodegradable polymers selected from the group consisting of PLCL, PLLA, PDLLA, PLGA, PLLCL, and combinations thereof, supporting diffusion-controlled drug release behavior.
Claims Coverage
The document provides one independent claim defining the coated implantable medical device with a three-layer coating structure and quantitative constraints on mTOR inhibitor loading and release. The dependent claims refine the independent claim with specific selections for the mTOR inhibitor, polymers, antioxidants, hydrophilic polymer identity, and additional release-fraction ranges.
Three-layer coated implantable medical device with mTOR inhibitor distribution
A coated implantable medical device consisting of a base layer on the device, a middle layer on the device, and a top layer, where the base layer and middle layer include one or more mTOR inhibitors dispersed in one or more biodegradable polymers (optionally with one or more antioxidants) and the top layer is mTOR inhibitor-free and selected from one or more hydrophilic polymers, or combinations of one or more hydrophilic polymers with one or more antioxidants.
Defined mTOR inhibitor-to-biodegradable polymer weight ratios across base and middle layers
The base layer has a weight ratio of one or more mTOR inhibitors to one or more biodegradable polymers in a range of from 10:90 to 30:70; the middle layer has a weight ratio in a range of from 15:85 to 40:60 and wherein the weight ratio of the one or more mTOR inhibitors is greater than in the base layer.
Selected mTOR inhibitor and biodegradable polymer sets
The one or more mTOR inhibitors are selected from the group consisting of everolimus, pimecrolimus, tacrolimus, zotarolimus, biolimus, rapamysin, and mixtures thereof, and the one or more biodegradable polymers in the base and middle layer are selected from the group consisting of PLCL, PLLA, PDLLA, PLGA, PLLCL, and combinations thereof.
mTOR inhibitor-free hydrophilic top layer with antioxidant concentration relative to total mTOR inhibitor
The top layer is mTOR inhibitor-free and includes one or more hydrophilic polymers and, optionally, one or more antioxidants, wherein a total antioxidant concentration of the one or more antioxidants in the top layer varies from 0.5 weight percent to 10 weight percent with respect to a total mTOR inhibitor concentration over the medical device.
Quantified total mTOR inhibitor concentration and release timing
The total mTOR inhibitor concentration over the medical device is in the range of from 0.7 to 3.00 μg/mm2, wherein the base layer has a higher total amount of the one or more mTOR inhibitors than the middle layer, and wherein from 10 to 30% of the total amount of the one or more mTOR inhibitors is released from the medical device in the first 24 hours after use with the remainder released over a period of time of 28 days or longer.
Claim coverage centers on a three-layer conformal coating in which mTOR inhibitors are dispersed in biodegradable polymer base and middle layers with specified weight-ratio relationships and total loading, while an mTOR inhibitor-free hydrophilic top layer optionally includes antioxidants with a defined antioxidant-to-mTOR relative concentration. The independent claim further requires a defined release fraction in the first 24 hours and sustained release for 28 days or longer.
Stated Advantages
Controlled diffusion-based drug release profile, including from 10 to 30% release in the first 24 hours with sustained release over a period of time of 28 days or longer.
Protection from moisture and chemical exposure via the multi-layer coating architecture, including the hydrophilic top layer.
Reduced burst and reduced local exposure issues associated with drug release behavior.
Antioxidant-stabilized mTOR inhibitor (including everolimus).
Documented Applications
Implantable medical device use of the coated device, including devices selected from stents, guide wires, heart valves, catheters, vena cava filters, vascular grafts, and stent grafts.
Interested in licensing this patent?