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

• US 9,492,594 B2
• Filed: 07/18/2014
• Issued: 11/15/2016
• 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:
  US14/335,823
• Publication Number:
  US 20160015862A1
• Time in Patent Office: 851 Days
• Field of Search: None
• US Class Current: 1/1
• 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 coating over an outer surface of the expandable portion, wherein the coating comprises;

a hydrophobic matrix, wherein the hydrophobic matrix 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;

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 first biodegradable or bioerodable polymer; and

wherein the hydrophobic matrix is configured to adhere to a luminal surface when the expandable portion is expanded, and transfer at least a portion of the plurality of micro-reservoirs to the luminal surface.

2. The catheter of claim 1, further comprising a release layer between the expandable portion and the coating, wherein the release layer is configured to release the coating from the expandable portion.

3. The catheter of claim 2, wherein the release layer comprises DSPE-mPEG350 or DSPE-mPEG500.

4. The catheter of claim 2, wherein the release layer has a surface concentration of about 0.1 μ

g/mm² to about 5 μ

g/mm².

5. The catheter of claim 1, further comprising a protective coating over the coating.

6. The catheter of claim 5, wherein the protective coating comprises a hydrophilic polymer, a carbohydrate, an amphiphilic polymer, a glycosoaminoglycan, or a crystallized sugar.

7. The catheter of claim 5, wherein the protective coating has a surface concentration of about 0.1 μ

g/mm² to about 5 μ

g/mm².

8. The catheter of claim 1, wherein the weight ratio of cholesterol to phospholipid is in the range of about 1:

2 to about 3;

1.

9. The catheter of claim 1, wherein the phospholipid with an acyl chain length of about 20 to about 34 is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol.

10. The catheter of claim 1, wherein the acyl chain phospholipid is selected from the group consisting of dieicosenoyl phosphatidylcholine (1,2-dieicosenoyl-sn-glycero-3-phosphocholine, C20:

1 PC), diarachidonoyl phosphatidylcholine (1,2-diarachidoyl-sn-glycero-3-phosphocholine, C20;

0 PC), dierucoyl phosphatidylcholine (1,2-dierucoyl-sn-glycero-3-phosphocholine, C22;

1 PC), didocosahexaenoyl phosphatidylcholine (1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, C22;

6 PC), heneicosenoyl phosphatidylcholine (1,2-heneicosenoyl-sn-glycero-3-phosphocholine, C21;

1 PC), and dinervonyl phosphatidylcholine (1,2-dinervonoyl-sn-glycero-3-phosphocholine, C24;

1 PC).

11. The catheter of claim 1, wherein the hydrophobic matrix comprises a cholesterol and a cationic phospholipid.

12. The catheter of claim 11, wherein the cationic phospholipid is phosphatidylethanolamine, dioleoylphosphatidylethanolamine (DOPE), or an amine derivative of phosphatidylcholine, each with an acyl chain length of about 20 to about 34.

13. The catheter of claim 1, wherein the hydrophobic matrix comprises DC-Cholesterol and a phospholipid.

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

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

16. The catheter of claim 15, wherein the plurality of micro-reservoirs has an active agent release kinetics with a half-life of at least 14 days.

17. The catheter of claim 1, wherein 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, glycosoaminoglycans, and combinations thereof.

18. 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.

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

20. The catheter of claim 1, wherein the first active agent is intermixed with or dispersed in the first biodegradable or bioerodable polymer.

21. The catheter of claim 1, wherein the hydrophobic matrix further comprises a PEG-lipid.

22. The catheter of claim 21, 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(polyethyleneglycol)-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).

23. The catheter of claim 21, wherein the PEG-lipid is about 1% to about 30% by weight of the hydrophobic matrix.

24. The catheter of claim 21, wherein the PEG-lipid is about 2% to about 25% by weight of the hydrophobic matrix.

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

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

g/mm² to about 10 μ

g/mm².

27. The catheter of claim 1, wherein the coating further comprises a second active agent outside of the plurality of micro-reservoirs.

28. The catheter of claim 27, 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.

29. The catheter of claim 1, wherein the coating is homogenous.