Heparin prodrugs and drug delivery stents formed therefrom

• US 9,375,445 B2
• Filed: 06/22/2009
• Issued: 06/28/2016
• Est. Priority Date: 06/18/2004
• 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, Ding, Ni
• Primary Examiner(s): Tran, Susan
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US12/489,205
• Publication Number:
  US 20090258029A1
• Time in Patent Office: 2,563 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/80 characterised by a special chemical form
• 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 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C09D 105/10 Heparin; Derivatives thereof

Abstract

A prodrug comprising a heparin and a drug is provided. The prodrug can be used to form a coating on a medical device. The prodrug can also be used with a polymeric material to form a coating on a medical device. The polymeric material can be a hydrophobic polymer, a hydrophilic polymer, a non-fouling polymer, or combinations thereof. The medical device can be implanted in a human being for the treatment of a disease such as atherosclerosis, thrombosis, restenosis, 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, or combinations thereof.

Claims

1. A coating composition comprising:

a prodrug, the prodrug comprising a drug, heparin, and a first polymer,

wherein the heparin is linked covalently to the first polymer and the drug,

wherein the covalent linkage between the drug and the heparin is either hydrolytically or enzymatically unstable,

wherein the drug is not pharmacologically active when linked to the heparin, and

wherein the first polymer is selected from the group consisting of poly(L-lysine-co-hyaluronic acid) (PLL-co-HA), poly(L-lysine-co-phosphoryl choline) (PLL-co-PC), poly(ethylimine-co-hyaluronic acid) (PEI-co-HA), poly(ethylimine-co-phosphoryl choline) (PEI-co-PC), poly(L-lysine-g-hyaluronic acid) (PLL-g-HA), poly(L-lysine-g-phosphoryl choline) (PLL-g-PC), poly(ethylimine-g-hyaluronic acid) (PEI-g-HA), and poly(ethylimine-g-phosphoryl choline) (PEI-g-PC).

2. The composition of claim 1, wherein the drug is selected from the group consisting of antiproliferative, anti-inflammatory, non-steroidal anti-inflammatory, and antimitotic drugs and combinations thereof.

3. The composition of claim 2, wherein the drug is selected from the group consisting of paclitaxel, docetaxel, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, (ABT-578, zotarolimus) and combinations thereof.

4. The composition of claim 3, wherein the heparin is a pentasaccharide.

5. The composition of claim 3, further comprising a second polymer selected from the group consisting of a hydrophilic polymer, a hydrophobic polymer, a non-fouling polymer, and combinations thereof.

6. The composition of claim 1, wherein the drug is linked directly to the first polymer.

7. The composition of claim 1, wherein the heparin is a pentasaccharide.

8. The composition of claim 7, further comprising a second polymer selected from the group consisting of a hydrophilic polymer, a hydrophobic polymer, a non-fouling polymer, and combinations thereof.

9. The composition of claim 1, further comprising a second polymer selected from the group consisting of a hydrophilic polymer, a hydrophobic polymer, a non-fouling polymer, and combinations thereof.