Heparin prodrugs and drug delivery stents formed therefrom

Patent metadata

Field	Value
Publication number	US-9364498-B2
Application number	US-48921909-A
Country	US
Kind code	B2
Filing date	Jun 22, 2009
Priority date	Jun 18, 2004
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

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.

First claim

What is claimed is:

1. A prodrug of a drug, said prodrug comprising the drug, heparin, and a polymer,
wherein the heparin is covalently linked to the polymer,
wherein the drug is covalently linked to the heparin,
wherein the drug is not pharmacologically active in the presence of the covalent linkage between the drug and the heparin,
wherein the covalent linkage of the drug to the heparin is either hydrolytically or enzymatically unstable,
wherein the covalent linkage between the drug and the heparin is hydrolytically or enzymatically cleaved under in vivo conditions, and
wherein the 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 prodrug of claim 1 , wherein the prodrug is an ester formed between a carboxyl group of the heparin and a hydroxyl group of the drug or between a carboxyl group of the drug and a hydroxyl group of heparin, wherein the drug is selected from the group consisting of paclitaxel, docetaxel, estradiol, tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), clobetasol, aspirin, and a combination thereof.

3. The prodrug of claim 1 , wherein the heparin is pentasaccharide.

4. A medical device comprising as a coating the prodrug of claim 1 .

5. A medical device comprising as a coating the prodrug of claim 2 .

6. The prodrug of claim 1 , wherein the heparin is a heparin modified with a hydrophobic counter-ion.

7. A medical device comprising as a coating the prodrug of claim 3 .

8. The medical device of claim 4 , further comprising a polymer selected from the group consisting of a hydrophilic polymer, a hydrophobic polymer, a non-fouling polymer, and combinations thereof.

9. A method of treating a disorder in a human being by implanting in the human being the medical device as defined in claim 4 ,
wherein the disorder is selected from the group consisting of 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, and combinations thereof.

Assignees

• Hossainy Syed Faiyaz Ahmed
• Ding Ni
• Abbott Cardiovascular Systems

Inventors

• Hossainy Syed Faiyaz Ahmed
• Ding Ni

Classifications

• A61L2300/236

  Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin · CPC title

• C08B37/0075

  Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• C09D105/10

  Heparin; Derivatives thereof · CPC title

• A61L2300/80

  characterised by a special chemical form · CPC title