Hyaluronic acid based copolymers

• US 9,101,697 B2
• Filed: 04/11/2014
• Issued: 08/11/2015
• Est. Priority Date: 04/30/2004
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Hossainy, Syed Faiyaz Ahmed, Michal, Eugene, Glauser, Thierry, Kwok, Connie, Pacetti, Stephen Dirk
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US14/251,489
• Publication Number:
  US 20140221418A1
• Time in Patent Office: 487 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• 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
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/10 Heparin; Derivatives thereof

Abstract

Hyaluronic acid (HA) conjugates or crosslinked HAs compositions for coating an implantable device are provided. The implantable device can be used for treating a disorder such as atherosclerosis, thrombosis, restenosis, high cholesterol, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof.

Claims

1. A hyaluronic acid (HA) conjugate comprising a moiety derived from HA and at least one component that is heparin or a moiety derived from heparin,

wherein the moiety derived from HA is a HA derivatized with a reactive agent selected from the group consisting of hydrazide, aziridine, epoxide, vinyl sulphone, and bis-succinimidyl;

wherein the HA conjugate is formed by coupling the moiety derived from HA and heparin or a moiety derived from heparin.

2. The HA conjugate of claim 1, wherein the moiety derived from heparin is a heparin derivatized with two or more hydrazides, aziridines, epoxides, vinyl sulphones, and aldehydes.

3. An implantable device comprising the HA conjugate of claim 1.

4. The implantable device of claim 3, further comprising a bioactive agent.

5. The implantable device of claim 4, wherein the bioactive agent is selected from the group consisting of ABT-578™

, paclitaxel, docetaxel, paclitaxel derivatives, tacrolimus, pimecrolimus, batimastat, mycophenolic acid, estradiol, clobetasol, dexamethasone, rapamycin, 40-O-(2-hydroxyl)ethyl-rapamycin (everolimus), 40-O-(3-hydroxyl)propyl-rapamycin, 40-O-[2-(2-hydroxyl)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), prodrugs thereof, co-drugs thereof, and combinations thereof.

6. A method of treating a disorder selected from the group consisting of atherosclerosis, thrombosis, restenosis, high cholesterol, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof, comprising:

implanting in a human being an implantable device comprising the HA conjugate of claim 1.

7. The HA conjugate of claim 1, wherein the heparin derivative is an alkali metal or alkaline-earth metal salts of heparin.

8. The HA conjugate of claim 7, the alkali metal or alkaline-earth metal salts of heparin is selected from the group consisting of sodium heparin, potassium heparin, lithium heparin, calcium heparin, magnesium heparin, and low molecular weight heparin.

9. The HA conjugate of claim 1, wherein the heparin derivative is selected from the group consisting of heparin sulfate, heparinoids, and heparin having a hydrophobic counter-ion.

10. The HA conjugate of claim 1, wherein the HA conjugate is end-capped with hydrophobic species.

11. The HA conjugate of claim 10, wherein the hydrophobic species is selected from the group consisting of stearate, laurate, palmitate, and oleate, fatty alcohols, and poly(ester amide) that optionally contains alkyl, amino acid, PEG or alcohol groups, polycaprolactone, polylactide, polyglycolide, polyhydroxyalkanoate (PHA), polydioxanone (PDS), or PHA-PEG.

12. The HA conjugate of claim 11, wherein the fatty alcohol is selected from the group consisting of hexanol, dodecanol, stanol, sterol, cholesterol, and cetyl.

13. The HA conjugate of claim 11, wherein the PHA is selected from the group consisting of poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-valerate) (PHBV), poly(3-hydroxyproprionate) (PHP), poly(3-hydroxyhexanoate) (PHH), poly(4-hydroxyacid), poly (4-hydroxybutyrate), poly(4-hydroxyvalerate), and poly(4-hydroxyhexanoate).