Catheter system for controllably releasing a therapeutic agent at a remote tissue site

• US 5,470,307 A
• Filed: 03/16/1994
• Issued: 11/28/1995
• Est. Priority Date: 03/16/1994
• Status: Expired due to Fees

• Current Assignee: Arnold W. Lindall
• Original Assignee: Arnold W. Lindall
• Inventors: Lindall, Arnold W.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): VANOVER, PERRY
• Application Number:
  US08/214,051
• Time in Patent Office: 622 Days
• Field of Search: 604/20, 604/28, 604/264-266, 604/890.1, 604/891.1, 604/892.1, 604/92, 604/93, 604/95-96, 604/83, 604/113, 604/51-53, 604/57, 604/48-49, 128/633-634, 128/898, 128/DIG. 3, 606/7, 606/194, 607/92
• US Class Current: 604/20
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/23 Carbohydrates
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent

Abstract

A catheter having a therapeutic agent chemically bonded to a substrate on its exterior surface using a linker which photolytically releases the agent upon exposure to light energy at an appropriate wavelength. The linker is attached to the substrate via a complementary chemical group, with the opposing end containing an aromatic ring with a nitro group in the ortho position relative to a methyl or ethyl group which is functionalized to accept a complementary bond to the therapeutic agent. The substrate may include materials such as glass, polyamide, polyester, polyolefin, polypropylene, polyurethane, or latex. The therapeutic agent may include peptides, proteins, steroids, carbohydrates, nucleotides, or other aliphatic or heterocyclic products, and may be bonded to a molecular lattice or meshwork to accommodate a high molecular concentration per unit area and the inclusion of ancillary compounds such as markers or secondary emitters.

Claims

1. A catheter for applying a therapeutic agent to a tissue site by selectively releasing said therapeutic agent in response to light energy emanating from a source and conducted through at least a portion of said catheter, said catheter comprising:

a catheter body, said catheter body having a surface including a substrate layer; and

a linker layer, said linker layer being chemically bonded to said substrate layer with the therapeutic agent being chemically bonded to said linker layer, the therapeutic agent being selectively released from said substrate layer by a photolytic chemical reaction occurring in response to exposure to the light energy emanating from the source and conducted through the portion of the catheter.

2. The catheter of claim 1 wherein the catheter body is a conventional medical catheter selected from the group including:

a percutaneous transluminal angiography (PTA) catheter, a percutaneous transluminal coronary angioplasty (PTCA) catheter, a vascular catheter, a peripheral vascular catheter, a thrombectomy catheter, an embolectomy catheter, a renal catheter, a esophageal catheter, a perfusion catheter, an upper gastrointestinal catheter, a lower gastrointestinal catheter, a bile duct catheter, a pancreatic duct catheter, a urethral catheter, a ureteral catheter, and a urogenital catheter.

3. The catheter of claim 1 wherein the catheter body is a fiber optic probe.

4. The catheter of claim 3 wherein the probe is a central nervous system probe.

5. The catheter of claim 1 wherein the catheter body defines a lumen.

6. The catheter of claim 1 wherein the at least a portion of the catheter body is fabricated from a polymer selected from the group comprising:

a polyethylene terephthalate, a polyethylene, a polyamide, a polyester, a polyolefin, a polypropylene, a polyurethane, a polystyrene, a polysulfone, and a latex.

7. The catheter of claim 6 wherein the polymer from which the catheter body is fabricated defines the surface of the catheter.

8. The catheter of claim 7 wherein the polymer defining the surface of the catheter is derivatized to form the substrate layer.

9. The catheter of claim 1 wherein the substrate layer has an exposed functional group selected from the group comprising:

a carboxyl, an amine, an hydroxyl, a sulfhydryl, a succinimide, and a maleimide.

10. The catheter of claim 1 further comprising:

a molecular lattice, said molecular lattice being disposed between and chemically bonded to the substrate layer and the therapeutic agent.

11. The catheter of claim 10 wherein the molecular lattice includes at least one branched chain, a bond to the substrate layer, and a plurality of bonding sites to which a plurality of molecules of the therapeutic agent are selectively bonded.

12. The catheter of claim 10 wherein the molecular lattice is a branched polyamino acid including a plurality of amino acids, said amino acids being selected from a group comprising:

a lysine, a cysteine, a glutamic acid, an alanine, and an aspartic alanine.

13. The catheter of claim 10 wherein an ancillary compound is bonded to the molecular lattice in addition to the therapeutic agent.

14. The catheter of claim 13 wherein the ancillary compound is a fluorescent marker compound.

15. The catheter of claim 1 wherein the linker layer is formed from a heterobifunctional agent.

16. The catheter of claim 15 wherein the heterobifunctional agent is covalently bonded to the therapeutic agent.

17. The catheter of claim 15 wherein the linker layer is formed from a 2 nitro benzyl compound.

18. The catheter of claim 15 wherein the substrate layer has an exposed functional group, the heterobifunctional agent being bonded to said exposed functional group, the heterobifunctional agent further including an aromatic ring having a nitro group, said nitro group being disposed in an ortho position relative to a methyl group or an ethyl group, said methyl group or said ethyl group being functionalized to accept a complementary bond to the therapeutic agent.

19. The catheter of claim 18 wherein the methyl group or the ethyl group are selected from the group comprising:

a methyl, an ethyl, an amino methyl, a 1-amino ethyl, a bromo methyl, a 1-bromo ethyl, a methyl hydrazone, a methyl hydrazine, a 1-ethyl hydrazone, a 1-ethyl hydrazine, a chlorocarbonyl methyl, and a 1-chlorocarbonyl ethyl.

20. The catheter of claim 15 wherein the linker layer is formed from a 2-nitro phenyl compound including an aromatic ring having an ortho position, a meta position, and a para position, a nitro phenyl group being disposed in said ortho position, said 2 nitro phenyl group having a first functionality, said 2-nitro phenyl compound having a second functionality disposed at said meta position or said para position.

21. The catheter of claim 1 wherein the therapeutic agent is selected from a group comprising:

a peptide, a protein, a carbohydrate, asteroid, a lipid, a nucleotide, an antisense nucleotide, a peptide fragment, a nucleotide fragment, and an antisense nucleotide fragment.

22. The catheter of claim 1 wherein the therapeutic agent is an antisense oligodeoxynucleotide.

23. The catheter of claim 1 wherein the therapeutic agent is a peptide fragment hirudin (54-65).

24. A method for applying a therapeutic agent to a tissue site, said method comprising the steps of:

providing a catheter having a catheter body and a surface including a substrate layer;

connecting a linker layer and the therapeutic agent to said substrate layer, said linker layer being chemically bonded to said substrate layer, the therapeutic agent being chemically bonded to said linker layer;

positioning at least a portion of said catheter body to which the therapeutic agent connected generally proximate to the remotely located tissue site; and

applying light energy to said substrate layer or said linker layer such that the therapeutic agent is selectively and responsively released from said substrate layer by a photolyric chemical reaction occurring in response to exposure to said light energy.