Coating for intraluminal expandable catheter providing contact transfer of drug micro-reservoirs

• US 10,098,987 B2
• Filed: 10/11/2016
• Issued: 10/16/2018
• Est. Priority Date: 07/18/2014
• Status: Active Grant

• Current Assignee: M.A. Med Alliance SA
• Original Assignee: M.A. Med Alliance SA
• Inventors: Ahlering, Michael Thomas, Yamamoto, Ronald Kenichi, Elicker, Robert John, Nguyen, Tien Thuy, Shulze, John Edwin, Zoethout, Jelle Jurjen
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Helm, Caralynne E
• Application Number:
  US15/290,931
• Publication Number:
  US 20170028105A1
• Time in Patent Office: 735 Days
• Field of Search: None
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/04 Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 29/126 having a macromolecular matrix
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/1031 Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 25/1027 : Making of balloon catheters
• 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
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

A coating for an expandable portion of a catheter comprising a hydrophobic matrix and a dispersed phase is disclosed. The dispersed phase comprises a plurality of micro-reservoirs dispersed in the hydrophobic matrix, wherein the plurality of micro-reservoirs comprises a first active agent and a first biodegradable or bioerodable polymer. A coating formulation and a method for forming the coating are also disclosed. A catheter comprising the coating on the expandable portion and a method for treating a condition are also provided.

Claims

1. A catheter comprising:

an expandable portion on an elongated body; and

a first coating over an outer surface of the expandable portion, wherein the first coating comprises;

a hydrophobic matrix, wherein the hydrophobic matrix comprises a cholesterol and a fatty acid; and

a dispersed phase comprising a plurality of micro-reservoirs dispersed in the hydrophobic matrix, wherein the plurality of micro-reservoirs comprises a first active agent and a biodegradable or bioerodable polymer; and

wherein at least a portion of the first coating will transfer to a luminal surface when the expandable portion is expanded at a treatment site, and transfers at least a portion of the plurality of micro-reservoirs to the luminal surface.

2. The catheter of claim 1, wherein the weight ratio of cholesterol to fatty acid is in the range of about 1:

2 to about 3;

1.

3. The catheter of claim 1, wherein the fatty acid is selected from the group consisting of lauric acid, lauroleic acid, tetradeadienoic acid, octanoic acid, myristic acid, myristoleic acid, decenoic acid, decanoic acid, hexadecenoic acid, palmitoleic acid, palmitic acid, linolenic acid, linoleic acid, oleic acid, vaccenic acid, stearic acid, eicosapentaenoic acid, arachadonic acid, mead acid, arachidic acid, docosahexaenoic acid, docosapentaenoic acid, docosatetraenoic acid, docosenoic acid, tetracosanoic acid, hexacosenoic acid, pristanic acid, phytanic acid, and nervonic acid.

4. The catheter of claim 1, wherein the cholesterol is dimethylaminoethane-carbamoyl cholesterol (DC cholesterol).

5. The catheter of claim 1, wherein the coating comprises about 10% to about 75% by weight of the plurality of micro-reservoirs.

6. The catheter of claim 1, wherein the plurality of micro-reservoirs has an average diameter of about 1.5 microns to about 8 microns.

7. The catheter of claim 1, wherein the plurality of micro-reservoirs has an average diameter of about 2.0 microns to about 6 microns.

8. The catheter of claim 1, wherein the plurality of micro-reservoirs has an active ingredient release kinetics with a half-life of at least 14 days.

9. The catheter of claim 1, wherein the the first biodegradable or bioerodable polymer is selected from the group consisting of polylactic acid, polyglycolic acid and their copolymers, polydioxanone, polycaprolactone, polyphosphazine, collagen, gelatin, chitosan, and glycosoaminoglycans.

10. The catheter of claim 1, wherein the first active agent is selected from the group consisting of paclitaxel, sirolimus, paclitaxel derivative, sirolimus derivative, paclitaxel analogues, sirolimus analogues, inhibitory RNA, inhibitory DNA, steroids, and complement inhibitors.

11. The catheter of claim 1 wherein the hydrophobic matrix further comprises a second active agent.

12. The catheter of claim 11, wherein the second active agent is selected from the group consisting of paclitaxel, sirolimus, paclitaxel derivative, sirolimus derivative, paclitaxel analogues, sirolimus analogues, inhibitory RNA, inhibitory DNA, steroids, and complement inhibitors.

13. The catheter of claim 11, wherein the first active agent and the second active agent are the same.

14. The catheter of claim 1, wherein the active agent is about 10% to about 50% by weight of the plurality of micro-reservoirs.

15. The catheter of claim 1, further comprising a polyethylene glycol-lipid (PEG-lipid).

16. The catheter of claim 15, wherein the PEG-lipid is selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-350 (DSPE-mPEG350), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-methoxy(polyethylene glycol)-350 (DPPE-mPEG350), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-350 (DOPE-mPEG350), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-550 (DSPE-mPEG550), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-550 (DPPE-mPEG550), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-500 (DOPE-mPEG550).

17. The catheter of claim 15, wherein the PEG-lipid is about 1% to about 10% by weight of the solids of the hydrophobic matrix.

18. The catheter of claim 1, further comprising one or more additives independently selected from penetrating enhancers and stabilizers.

19. The catheter of claim 1, wherein the coating has a surface concentration of about 1 μ

g/mm² to about 10 μ

g/mm².

20. A catheter comprising:

an expandable portion on an elongated body;

a first coating of claim 1 over the expandable portion; and

a release layer between the expandable portion and the coating, wherein at least a portion of the first coating will be released from the expandable portion when the expandable portion is expanded at a treatment site.

21. The catheter of claim 20, wherein the release layer comprises DSPE-mPEG350 or DSPE-mPEG500.

22. The catheter of claim 20, wherein the release layer has a surface concentration of about 0.1 μ

g/mm² to about μ

g/mm².

23. The catheter of claim 20, further comprising a second protective coating over the first coating.

24. The catheter of claim 20, wherein the protective coating comprises a hydrophilic polymer, a carbohydrate, or an amphiphilic polymer.

25. The catheter of claim 23, wherein the protective coating is a glycosaminoglycan or a crystallized sugar.

26. The catheter of claim 23, wherein the protective coating has a surface concentration of about 0.1 μ

g/mm² to about 5 μ

g/mm².

42. A method for treating or preventing a condition at a treatment site, wherein the condition is selected from the group consisting of atherosclerosis, stenosis or reduction in luminal diameter in a diseased blood vessel, restenosis, and in-stent restenosis, comprising:

advancing a catheter of claim 1 to the treatment site, wherein the coating comprises an effective amount of the first active agent for treating or preventing the condition;

expanding the expandable portion to allow contact between the coating and a tissue at the treatment site;

collapsing the expandable portion; and

removing the catheter.

43. The method of claim 42, wherein the contact between the tissue and the coating results in a transfer of at least a portion of a coating on the expandable portion to the treatment site.

44. The method of claim 42, further comprising maintaining the contact between the expandable portion and the coating for a period of from about 30 to about 120 seconds.

27. A method for coating an expandable portion of a catheter such that at least a portion of the coating transfers to a luminal surface at a treatment site upon expansion of the expandable portion, the method comprises:

disposing a coating formulation onto the surface of an expanded expandable portion of the catheter wherein the coating formulation comprises;

a plurality of micro-reservoirs, wherein the plurality of micro-reservoirs comprise a first active agent intermixed with or dispersed in a biodegradable or bioerodable polymer;

at least one hydrophobic compound wherein the hydrophobic compound comprises a cholesterol and a fatty acid or a cholesterol and a phospholipid, wherein the phospholipid comprises an acyl chain phospholipid with an acyl chain length of about 20 to about 34; and

a fluid, wherein the fluid is selected from the group consisting of pentane, hexane, heptane, heptane, and fluorocarbon mixture, alcohol and fluorocarbon mixture, and alcohol and water mixture; and

evaporating the fluid; and

collapsing the expandable portion; and

wherein the plurality of micro-reservoirs are dispersed in a hydrophobic matrix formed by the at least one hydrophobic compound.

28. The method of claim 27 wherein the plurality of micro-reservoirs is about 10% to about 75% by weight of the solids of the coating formulation.

29. The method of claim 27, wherein the coating formulation further comprises a second active agent outside of the plurality of micro-reservoirs.

30. The method of claim 27, wherein the active agent is selected from the group consisting of paclitaxel, sirolimus, paclitaxel derivative, sirolimus derivative, paclitaxel analogues, sirolimus analogues, inhibitory RNA, inhibitory DNA, steroids, and complement inhibitors.

31. The method of claim 27, wherein the at least one hydrophobic compound comprises a cholesterol and a fatty acid.

32. The method of claim 31 wherein the weight ratio of cholesterol to fatty acid is in the range of about 1:

2 to about 3;

1.

33. The method of claim 31, wherein the fatty acid is selected from the group consisting of lauric acid, lauroleic acid, tetradeadienoic acid, octanoic acid, myristic acid, myristoleic acid, decenoic acid, decanoic acid, hexadecenoic acid, palmitoleic acid, palmitic acid, linolenic acid, linoleic acid, oleic acid, vaccenic acid, stearic acid, eicosapentaenoic acid, arachadonic acid, mead acid, arachidic acid, docosahexaenoic acid, docosapentaenoic acid, docosatetraenoic acid, docosenoic acid, tetracosanoic acid, hexacosenoic acid, pristanic acid, phytanic acid, and nervonic acid.

34. The method of claim 27 wherein the at least one hydrophobic compound comprises a cholesterol and a phospholipid, wherein the phospholipid comprises an acyl chain phospholipid with an acyl chain length of about 20 to about 34.

35. The method of claim 34 wherein the weight ratio of cholesterol to phospholipid is in the range of about 1:

2 to 3;

1.

36. The method of claim 34 wherein the phospholipid is dinervonicphosphatidylcholine, heneicosenoylphosphatidylcholine, or dierucoylphosphatidylcholine.

37. The method of claim 27 wherein the cholesterol is dimethylaminoethane-carbamoyl cholesterol (DC cholesterol).

38. The method of claim 27, wherein the solids content comprising a plurality of micro-reservoirs and at least one hydrophobic compound has a weight concentration of about 2 to 7%.

39. The method of claim 27, wherein the coating formulation further comprises a polyethylene glycol-lipid (PEG-lipid).

40. The method of claim 27, wherein disposing the formula comprises spray coating, dip coating, roll coating, electrostatic deposition, printing, pipetting, or dispensing.

41. The method of claim 27, wherein an additional release layer is disposed between the expandable portion and the coating.