TISSUE ADHESIVE COATINGS FOR DRUG COATED BALLOON

• US 20140277399A1
• Filed: 03/15/2013
• Published: 09/18/2014
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Pacetti, Stephen D., Stankus, John J.
• Granted Patent: US 9,782,516 B2
• Time in Patent Office: Days
• US Class Current: 623/1.42
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3695 characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this A61L27/3687, A61L27/3691 take precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A therapeutic formulation is described for a drug delivery balloon comprising a therapeutic formulation which includes a therapeutic agent and an adhesion additive. The adhesion additive promotes adhesion of the therapeutic formulation a vessel wall of a subject. A system and a method of manufacturing a system including an expandable member having a working length with the therapeutic formulation disposed along at least a portion of the working length is also provided.

Claims

1. A system for delivering a therapeutic agent to a vessel wall of a subject, comprising:

an expandable member having a distal end, a proximal end, and a working length therebetween; and

a therapeutic formulation disposed on at least a portion of the working length of the expandable member, the formulation comprising a therapeutic agent and an adhesion additive, wherein the adhesion additive promotes adhesion of the therapeutic formulation to the vessel wall.

2. The system of claim 1, wherein the adhesion additive promotes fibrin or thrombus formation on the vessel wall of the subject.

3. The system of claim 1, wherein the adhesion additive comprises a polycationic polymer, a hemostat, a polyanionic polymer, or combinations thereof.

4. The system of claim 3, wherein the adhesion additive comprises a polycationic polymer.

5. The system of claim 4, wherein the polycationic polymer is selected from the group consisting of polyethyeneimine, polyallylamine, chitosan, poly-N-acetylglucosamine, poly(L-lysine), poly(D-lysine), poly(L-arginine), poly(D-arginine), poly(L-histidine), poly(D-histidine), gelatin, collagen, urinary bladder matrix, small intestinal submucosa, a decellularized extra-cellular matrix based material, and combinations thereof.

6. The system of claim 5, wherein the polycationic polymer is selected from the group consisting of polyethyleneimine, polyallylamine, poly(L-lysine), poly(D-lysine), poly(L-arginine), poly(D-arginine), poly(L-histidine), poly(D-histidine) gelatin, collagen, urinary blabber matrix, small intestine submucosa, and combinations thereof.

7. The system of claim 4, wherein the therapeutic agent is zotarolimus, and the polycationic polymer is polyethyeneimine.

8. The system of claim 7, wherein the ratio of zotarolimus:

polyethyeneimine is about 1;

1 by weight.

9. The system of claim 4, wherein the therapeutic agent is zotarolimus, and the polycationic polymer is poly(L-lysine).

10. The system of claim 9, wherein the ratio of zotarolimus:

poly(L-lysine) is about 1;

1 by weight.

11. The system of claim 3, wherein the adhesion additive comprises at least one hemostat.

12. The system of claim 11, wherein the at least one hemostat is selected from the group consisting of inorganic hemostats, small molecule hemostats, peptide hemostats, or combinations thereof.

13. The system of claim 12, wherein the at least one hemostat is an inorganic hemostat selected from the group consisting of particulate hydroyxyapatite, calcium chloride, zinc chloride, silver nitrate, ferric sulphate, aluminum trichloride, and combinations thereof.

14. The system of claim 12, wherein the at least one hemostat is a small molecule hemostat selected from tranexamic acid, aminocaproic acid, or a combination thereof.

15. The system of claim 12, wherein the at least one hemostat is a peptide hemostat.

16. The system of claim 15, wherein the peptide hemostat is aprotinin.

17. The system of claim 11, wherein the therapeutic agent is sirolimus and the hemostat is tranexamic acid.

18. The system of claim 17, wherein the ratio of sirolimus:

tranexamic acid is about 1;

1 by weight.

19. The system of claim 3, wherein the adhesion additive comprises at least one polyanionic polymer.

20. The system of claim 19, wherein the polyanionic polymer is selected from the group consisting of poly(acrylic acid), poly(methacrylic acid), carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl cellulose-cysteine, poly(L-aspartic acid), poly(D-aspartic acid), poly(L-aspartic acid) sodium salt, poly(L-glutamic acid), poly(D-glutamic acid), poly(L-glutamic acid) sodium salt, and combinations thereof.

21. The system of claim 19, wherein the therapeutic agent is zotarolimus, and the polyanionic polymer is poly(L-glutamic acid).

22. The system of claim 21, wherein the formulation further comprises glycerol.

23. The system of claim 22, wherein the ratio of zotarolimus:

poly(L-glutamic acid);

glycerol is about 2;

1;

0.4 by weight.

24. The system of claim 19, wherein the therapeutic agent is everolimus, and the polyanionic agent is poly(L-glutamic acid).

25. The system of claim 24, wherein the poly(L-glutamic acid) is combined with dopamine in the form of poly(L-glutamic acid)-dopamine.

26. The system of claim 25, wherein the ratio of everolimus:

poly(L-glutamic acid)-dopamine is about 2;

1 by weight.

27. The system of claim 19, wherein the therapeutic agent is paclitaxel, and the polyanionic polymer is sodium carboxymethyl cellulose.

28. The system of claim 27, wherein the formulation further comprises DMSO.

29. The system of claim 28, wherein the ratio of paclitaxel:

sodium carboxymethyl cellulose;

DMSO is about 1;

1;

0.2 by weight.

30. The system of claim 1, wherein the therapeutic agent is selected from the group consisting of zotarolimus, sirolimus, rapamycin, everolimus, biolimus, myolimus, novolimus, temsirolimus, deforolimus, merilimus, sirolimus derivatives, tacrolimus, pimecrolimus, dexamethasone, estradiol, paclitaxel, protaxel, taxane, docetaxel, angiopeptin, angiotensin converting enzyme inhibitors, captopril, cilazapril, lisinopril, calcium channel blockers, nifedipine, amlodipine, cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem, verapamil, fibroblast growth factor antagonists, fish oil, omega 3-fatty acid, histamine antagonists, lovastatin, topoisomerase inhibitors, etoposide, topotecan, antiestrogens, tamoxifen, derivatives and analogues thereof, and combinations thereof.

31. The system of claim 1, wherein the therapeutic agent is a cytostatic agent.

32. The system of claim 31, wherein the cytostatic agent is crystalline.

33. The system of claim 31, wherein cytostatic agent is selected from the group consisting of zotarolimus, sirolimus, rapamycin, everolimus, biolimus, myolimus, novolimus, temsirolimus, deforolimus, merilimus, sirolimus derivatives, tacrolimus, pimecrolimus, derivatives and analogues thereof, and combinations thereof.

34. The system of claim 1, wherein the formulation further comprises at least one compound selected from the group consisting of surfactants, emulsifiers, solvents, plasticizers, and combinations thereof.

35. The system of claim 34, wherein the plasticizer is selected from the group consisting of dimethysulfoxide (DMSO), polyethylene glycol (molecular weight <

40K), propylene glycol, glycerol, N-Methyl-2-pyrrolidone (NMP), dimethylacetamide (DMAC), benzyl alcohol, fatty alcohols, benzyl benzoate, phenoxyethanol, and combinations thereof.

36. The system of claim 34, wherein the solvent is selected from the group consisting of acetone, 2-butanone, cyclopentanone, cyclohexanone, diethyl ether, dipropyl ether, diisopropyl ether, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tertiary-butanol, toluene, xylene, pentane, hexane, cyclohexane, heptane, dimethylformamide (DMF), dimethylacetamide (DMAC), and combinations thereof.

37. The system of claim 1, wherein the formulation further comprises a non-ionic polymer.

38. The system of claim 37, wherein the non-ionic polymer is selected from the group consisting of polyvinylpyrrolidone (PVP), silk-elastin like polymer, poly(vinyl alcohol), poly(ethylene glycol) (PEG), pluronics (PEO-PPO-PEO), poly(vinyl acetate), poly(ethylene oxide) (PEO), PVP-vinyl acetate (copovidone), polysorbate 80 (Tween 80), polysorbate 20 (Tween 20), hydroxyl alkyl celluloses, and combinations thereof.

39. The system of claim 37, wherein the adhesion additive increases tissue adhesion of the non-ionic polymer to the vessel wall of the subject.

40. The system of claim 1, further comprising a prosthesis mounted on the expandable member.

41. The system of claim 40, wherein the prosthesis is a stent.

42. The system of claim 1, wherein the expandable member is an angioplasty balloon.

43. A method for manufacturing a system for delivering a therapeutic agent to a vessel wall of a subject, comprising:

(a) providing a system comprising an expandable member having a distal end, a proximal end, and a working length therebetween; and

(b) disposing a therapeutic formulation to at least a portion of the working length of the expandable member, wherein the formulation comprises a therapeutic agent and an adhesion additive;

wherein the adhesion additive promotes adhesion of the therapeutic formulation to the vessel wall.