Biodegradable implantable medical devices, methods and systems
The invention provides implantable intraluminal medical devices that are fabricated of biodegradable materials. The invention further provides methods of treatment utilizing the devices.
1 . An implantable intraluminal medical device comprising a body member fabricated of a biodegradable amphiphilic block copolymer comprising hydrophilic blocks and hydrophobic blocks.
2 . The medical device according to claim 1 wherein the body member comprises an intravascular medical device.
3 . The medical device according to claim 2 wherein the intravascular medical device is selected from stents, stent grafts, shunts, anastamosis devices, occlusion devices, septal defect treatment devices, and closure devices.
4 . The medical device according to claim 1 wherein the body member is configured for extravascular placement within a patient.
5 . The medical device according to claim 4 wherein the body member is configured for placement within the brain, gastrointestinal, duodenum, biliary ducts, esophagus, urethra, lymphatic vessels, reproductive tracts, trachea, respiratory ducts, and otological passages.
6 . The medical device according to claim 1 wherein the hydrophilic blocks comprise polyalkylene glycol.
7 . The medical device according to claim 6 wherein the polyalkylene glycol is selected from the group polyethylene glycol, polypropylene glycol, and polybutylene glycol.
8 . The medical device according to claim 7 wherein the polyalkylene glycol is selected from the group polyethylene glycol terephthalate, polypropylene glycol terephthalate, and polybutylene glycol terephthalate.
9 . The medical device according to claim 6 wherein the polyalkylene glycol blocks comprise polymers having a formula:
—OLO—CO—R—CO—
wherein L is a divalent organic radical remaining after removal of terminal hydroxyl groups from a poly(oxyalkylene)glycol, O represents oxygen, C represents carbon, and R is a substituted or unsubstituted divalent radical remaining after removal of carboxyl groups from a dicarboxylic acid.
10 . The medical device according to claim 6 wherein the hydrophobic blocks comprise aromatic polyester formed from an alkylene glycol having 2 to 8 carbon atoms and a dicarboxylic acid.
11 . The medical device according to claim 10 wherein the polyester is selected from the group polyethylene terephthalate, polypropylene terephthalate, and polybutylene terephthalate.
12 . The medical device according to claim 10 wherein the aromatic polyester blocks comprise polymers having a formula:
—OEO—CO—R—CO—
wherein E is an organic radical selected from the group of substituted or unsubstituted alkylene radical shaving 2 to 8 carbon atoms, and a substituted or unsubstituted ether moiety, O represents oxygen, C represents carbon, and R is a substituted or unsubstituted divalent aromatic radical.
13 . The medical device according to claim 1 wherein the amphiphilic block copolymer comprises polyethylene glycol/polybutylene terephthalate block copolymer.
14 . The medical device according to claim 1 wherein the amphiphilic block copolymer includes one or more bioactive agents.
15 . The medical device according to claim 14 wherein the bioactive agent is selected from antiproliferative agents, anti-inflammatory agents, inhibitors of angiogenesis, hormonal agents, or a combination of any two or more of these.
16 . The medical device according to claim 15 wherein the antiproliferative agent is selected from taxol, sirolimus (rapamycin), analogues of rapamycin (“rapalogs”), tacrolimus, ABT-578 from Abbott, everolimus, paclitaxel, taxane, vinorelbine.
17 . The medical device according to claim 15 wherein the anti-inflammatory agent is selected from hydrocortisone, hydrocortisone acetate, dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, fluoromethalone, betamethasone, triamcinolone, triamcinolone acetonide.
18 . The medical device according to claim 15 wherein the inhibitor of angiogensis is selected from angiostatin, anecortave acetate, thrombospondin, anti-VEGF antibody such as anti-VEGF fragment.
19 . The medical device according to claim 15 wherein the hormonal agent is selected from estrogen, estradiol, progesterol, progesterone, insulin, calcitonin, parathyroid hormone, peptide and vasopressin hypothalamus releasing factor.
20 . The medical device according to claim 1 wherein the body member has a minimum compression resistance of 5 Newtons.
21 . The medical device according to claim 1 wherein the body member has a minimum tensile strength of 500 psi.
22 . The medical device according to claim 1 wherein the body member has a minimum tensile modulus of 6000 psi.
23 . The medical device according to claim 1 further comprising a coating on a surface of the body member.
24 . The medical device according to claim 23 wherein the coating is provided on a portion of the body member surface.
25 . The medical device according to claim 23 wherein the coating comprises a biodegradable polymer selected from an amphiphilic copolymer having hydrophilic blocks and hydrophobic blocks, polylactic acid, copolymers of polylactic acid with glycolic acid, and polycarbonates.
26 . The medical device according to claim 1 further comprising a sheath.
27 . The medical device according to claim 1 further comprising microparticles.
28 . The medical device according to claim 1 further comprising one or more nondegradable fibers.
29 . The medical device according to claim 14 configured to release bioactive agent for a period of two weeks or more.
30 . The medical device according to claim 29 configured to release bioactive agent for a period of four weeks or more.
31 . A method of making a device for the controlled release of bioactive agent, the method comprising steps of providing a biodegradable amphiphilic block copolymer comprising hydrophilic blocks and hydrophobic blocks, and forming the copolymer into an implantable intraluminal medical device.
32 . The method according to claim 31 wherein the step of forming the copolymer into an implantable intraluminal medical device is accomplished by dip coating a substrate in the copolymer solution.
33 . A method for delivery of bioactive agent to a patient in a controlled manner, the method comprising steps of providing an implantable intraluminal device to a patient, the device comprising a body member fabricated of a polymer matrix comprising one or more bioactive agents and a biodegradable amphiphilic block copolymer comprising hydrophilic blocks and hydrophobic blocks.
34 . The method according to claim 33 further comprising a step of allowing the device to remain in the patient for a selected period of time, wherein the device is configured to degrade upon implantation for a degradation period, and wherein bioactive agent is released in a controlled manner for a bioactive agent release period, the release period constituting at least a portion of the degradation period.
35 . The method according to claim 34 wherein release period comprises 50% or less of the degradation period.
36 . The method according to claim 34 wherein the degradation period is in the range of 0.5 to 2 years.