CONTROLLED DELIVERY OF MOLECULES FROM A BIOINTERFACE

• US 20120258162A1
• Filed: 04/07/2011
• Published: 10/11/2012
• Est. Priority Date: 04/07/2011
• Status: Abandoned Application

• Current Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Original Assignee: Empire Technology Development LLC (Allied Inventors Management, LLC)
• Inventors: Tapsak, Mark A.
• Application Number:
  US13/202,682
• Publication Number:
  US 20120258162A1
• Time in Patent Office: Days
• US Class Current: 424/424
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 23/00 Anaesthetics
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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
• 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

Disclosed are methods and apparatuses for delivery of bioactive molecules. The drug delivery systems include an implantable medical device which significantly reduces or suppresses adverse biological responses associated with implantable devices and also promotes vascularization in tissues surrounding the implanted device. The disclosure also relates to drug delivery systems designed to vary the rate of delivery of bioactive molecules with a change in the physiological environment.

Claims

1. A drug delivery system comprising an implantable medical device configured to include a biointerface comprising a polymer and a bioactive molecule attached to the polymer via a silyl ether linker.

2. The drug delivery system of claim 1, wherein the silyl ether linker has the formula

3. The drug delivery system of claim 2, wherein R₁ and R₂ are independently selected from substituted or unsubstituted methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, aminomethyl, aminopropyl, trimethylaminopropyl, 4,5-dihydroimidazolyl propyl, carboxymethyl, carboxypropyl, phenyl, or benzyl groups.

4. The drug delivery system of claim 1, wherein the silyl ether linker is 3-aminopropyl methoxy silyl ether.

5. The drug delivery system of claim 1, wherein the bioactive molecule is selected from a group consisting of anti-inflammatory agents, angiogenic molecules, anti-infective agents, anesthetics, growth factors, adjuvants, wound factors, resorbable device components, immunosuppressive agents, antiplatelet agents, anticoagulants, ACE inhibitors, cytotoxic agents, anti-barrier cell compounds, vascularization compounds, and anti-sense molecules.

6. The drug delivery system of claim 1, wherein the bioactive molecule is selected from the group consisting of monobutyrin, S1P (sphingosine-1-phosphate), cyclosporin A, anti-thrombospondin-2, rapamycin (and its derivatives), and dexamethasone.

7. The drug delivery system of claim 1, wherein the polymer at least partially coats the implantable medical device to form a biointerface membrane.

8. The drug delivery system of claim 7, wherein the polymer coating forms a porous biointerface membrane.

9. The drug delivery system of claim 1, wherein the polymer is selected from the group consisting of silicone, polyurethane, polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, polylactone, polyamide, and polyacrylate.

10. The drug delivery system of claim 1, wherein the polymer is a block copolymer, a random copolymer, a graft copolymer, or a biostable polymer.

11. The drug delivery system of claim 1, wherein the bioactive molecule is an anti-inflammatory agent or an angiogenic molecule.

12. The drug delivery system of claim 1, wherein the bioactive molecule is a small bioactive molecule.

13. The drug delivery system of claim 1, wherein the silyl ether linker is hydrolyzable at a pH of less than 7.

14. The drug delivery system of claim 1, wherein the implantable medical device is at least partially coated with silicone, and wherein the silicone is linked to the bioactive molecule via a silyl ether linker.

15. The drug delivery system of claim 14, wherein the bioactive molecule is monobutyrin.

16. The drug delivery system, of claim 15, wherein the silyl ether linker and bioactive molecule have the structure:

17. The drug delivery system of claim 16, wherein R₁ is an aminopropyl group and R₂ is a methyl group.

18. The drug delivery system of claim 1 wherein the implantable medical device is selected from a stent, glucose sensor, ocular implant, breast implant, penile implant, cosmetic implant, orthopedic implant, and cardioverter-defibrilator.

19. A method comprising releasing a bioactive molecule from a drug delivery system at a pH of less than 7, wherein the drug delivery system comprises an implantable medical device configured to include a biointerface comprising a polymer and a bioactive molecule attached to the polymer via a silyl ether linker.

20. The method of claim 19, wherein the bioactive molecule is an anti-inflammatory agent or an angiogenic molecule.

21. The method of claim 19, wherein the medical device is implanted in a host.