Implantable or insertable therapeutic agent delivery device

• US 20030077253A1
• Filed: 11/25/2002
• Published: 04/24/2003
• Est. Priority Date: 07/13/2000
• Status: Abandoned Application

• Current Assignee: Maria Palasis
• Original Assignee: Maria Palasis
• Inventors: Palasis, Maria
• Application Number:
  US10/302,830
• Publication Number:
  US 20030077253A1
• Time in Patent Office: Days
• US Class Current: 424/93.2
• 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 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 herein is an implantable or insertable therapeutic agent delivery device comprising a coating material provided on at least a portion of said device, said coating material prohibiting substantial release therefrom of a therapeutic agent at or below about a physiological pH and allowing substantial release therefrom of a therapeutic agent at or above about said physiological pH. Also disclosed herein are coating materials for the implantable or insertable therapeutic agent delivery device. The coating materials are preferably polymers derivatized to contain moieties that are cationically charged at a pH below their pKa values and which thus can attract negatively charged therapeutically agents at pH values below their pKa values and which become predominantly uncharged at pH values above about their pKa values and thus substantially release the negatively charged therapeutic agents at such pH values, which are preferably about physiological pH. Also disclosed are methods of derivatizing a polymer to contain such moieties and methods of providing a coating of the derivatized polymer onto at least a portion of a surface of an implantable or insertable therapeutic agent delivery device.

Claims

1. An implantable or insertable therapeutic agent delivery device comprising a coating material provided on at least a portion of said device, said coating material prohibiting substantial release therefrom of a therapeutic agent at or below about a physiological pH and allowing substantial release therefrom of a therapeutic agent at or above about said physiological pH.

2. The device of claim 1 wherein said coating material further comprises said therapeutic agent.

3. The device of claim 2 wherein said therapeutic agent is negatively charged and said coating material comprises moieties that carry a positive charge at a pH at or below about said physiological pH and that are substantially uncharged at or above about said physiological pH.

4. The device of claim 3 wherein said negatively charged therapeutic agent is selected from the group consisting of DNA, RNA, nucleotides, proteins, oligopeptides, viruses, nonviral vectors, and drugs.

5. The device of claim 3 wherein said physiological pH is in the range of from about 7.2 to about 7.6.

6. The device of claim 5 wherein said physiological pH is about the pH of mammalian blood.

7. The device of claim 6 wherein said pH is about 7.4.

8. The device of claim 3 wherein said coating material comprises a polymeric material.

9. The device of claim 8 wherein said polymeric material comprises a hydrogel polymer.

10. The device of claim 9 wherein said hydrogel polymer comprises a poly(acrylic acid) polymer.

11. The device of claim 10 wherein said moieties are provided by at least one compound selected from the group consisting of aminoethyl pyridine or aminopropyl imidazole.

12. The device of claim 1 which is a stent or balloon catheter.

13. A method of delivering a therapeutic agent to a mammal comprising implanting or inserting the device of claim 1 into a mammal.

18. The method of claim 13 wherein said compound has a pKa less than about a physiological pH.

14. A method of derivatizing a polymer comprising reacting, in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, carboxyl groups in said polymer with a compound containing a moiety that carries a positive charge at or below about a physiological pH and that is substantially uncharged above about said physiological pH.

15. The method of claim 14 wherein said physiological pH is in the range of from about 7.2 to about 7.6.

16. The method of claim 15 wherein said physiological pH is about the pH of mammalian blood.

17. The method of claim 16 wherein said pH is about 7.4.

19. The method of claim 14 wherein said compound bears an amino group.

20. The method of claim 19 wherein said compound is selected from the group consisting of aminoethyl pyridine or aminopropyl imidazole.

21. A polymer made by the method of claim 14.

22. A method of coating at least a portion of an implantable or insertable medical device comprising contacting said medical device with a coating material that prohibits substantial release therefrom of a therapeutic agent at or below about a physiological pH and allows substantial release therefrom of a therapeutic agent at or above about said physiological pH.

23. The method of claim 22 wherein said medical device is contacted with said coating material by a method selected from the group consisting of dipping said device into or spraying onto said device a solution or suspension of said coating material.

24. A method of coating at least a portion of an implantable or insertable medical device comprising contacting said medical device with a polymer and subsequently reacting, in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, carboxyl groups in said polymer with a compound containing a moiety that carries a positive charge at or below about a physiological pH and that is substantially uncharged at or above about said physiological pH, thereby forming a coating on at least a portion of the implantable or insertable medical device which prohibits substantial release therefrom of a therapeutic agent at or below about a physiological pH and which allows substantial release therefrom of a therapeutic agent at or above about said physiological pH.