DRUG-ELUTING MEDICAL IMPLANTS

• US 20180311415A1
• Filed: 05/01/2017
• Published: 11/01/2018
• Est. Priority Date: 05/01/2017
• Status: Active Grant

• Current Assignee: Lyra Therapeutics, Inc.
• Original Assignee: 480 Biomedical, Inc.
• Inventors: Concagh, Danny, You, Changcheng
• Granted Patent: US 10,201,639 B2
• Time in Patent Office: Days
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91575 connected peak to trough
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0014 using shape memory or superelastic materials, e.g. nitinol
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2230/0091 helically-coiled or spirally-coiled, i.e. having a 2-D spiral cross-section
• CPC Class Codes: A61F 2250/003 differing in adsorbability or resorbability, i.e. in adsorption or resorption time
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• 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 2400/16 Materials with shape-memory or superelastic properties
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Disclosed are medical implants for placement within a lumen of a patient. The implants comprise a polymer and drug-coated metal structure having a tubular configuration and designed to deliver the drug to target tissue at tailored linear drug elution rate.

Claims

1. A coated stent comprising (a) a tubular metallic substrate, (b) a first coating at least partially covering said substrate, said first coating comprising a first biodegradable polymer or blend of biodegradable polymers, and paclitaxel, wherein the total amount of paclitaxel in the stent is in the range of from 10 ug/10 mm length of stent to 80 ug/10 mm length of stent, and (c) a second coating at least partially covering said first coating, said second coating comprising a second biodegradable polymer or blend of biodegradable polymers, said second coating not containing a therapeutic agent,

wherein said first biodegradable polymer or blend of biodegradable polymers is the same or different from the second biodegradable polymer or blend of biodegradable polymers;

and

wherein the first coating thickness is from 1 to 15 microns and the second coating thickness is from 1 to 35 microns.

2. The coated stent of claim 1, wherein the first coating is configured to release a quantity of paclitaxel equal to 12.5 ng/mm² of stent surface area per day or less, during a period of from one to four days of submersion in a pH 7.4 phosphate-buffered saline buffer solution containing 2 wt % sodium dodecyl sulfate at 37°

C. under action of a rotary shaker, when the buffer solution is removed completely weekly for paclitaxel quantification and replaced with fresh buffer solution.

3-10. -10. (canceled)

11. A coated stent comprising (a) a tubular metallic substrate, (b) a first coating at least partially covering said substrate, said coating comprising a blend of poly(L-lactide-co-c-caprolactone) (PLCL), poly(L-lactide) (PLA), and paclitaxel and (c) a second coating at least partially covering said first coating, said second coating comprising PLCL and PLA, wherein the first coating comprises 10 to 99 wt percent of PLCL, 1 to 90 wt percent of PLA and paclitaxel and wherein said second coating does not contain a therapeutic agent, wherein the total amount of paclitaxel in the stent is in the range of from 10 ug/10 mm length of stent to 80 ug/10 mm length of stent.

12. The coated stent of claim 11, wherein the first coating is configured to release paclitaxel such that the quantity of paclitaxel released, based on a total amount of paclitaxel in the coated stent, ranges from 2% to 4% each week from 6 weeks to 20 weeks of submersion in a pH 7.4 phosphate-buffered saline buffer solution containing 2 wt % sodium dodecyl sulfate at 37°

C. under action of a rotary shaker, when the buffer solution is removed weekly for paclitaxel quantification and replaced with fresh buffer solution.

15. The coated stent of claim 11, wherein said tubular body comprises at least one strand, the at least one strand forming a plurality of intersections at which portions of the at least one strand overlap with each other.

16. The coated stent of claim 15, wherein the helical metallic strands comprise nitinol.

17. The coated stent of claim 11, wherein the PLCL has a molar percentage of lactide ranging from 60% to 80% and a molar percentage of caprolactone ranging from 20% to 40%.

18. The coated stent of claim 11, wherein the weight ratio of PLCL to PLA in each of the first coating and the second coating ranges from 15:

85 to 35;

65.

20. The coated stent of claim 11, wherein the weight ratio of PLCL to PLA in each of the first coating and the second coating ranges from 40:

60 to 60;

40.

21. The coated stent of claim 11, wherein the weight ratio of PLCL to PLA in each of the first coating and the second coating ranges from 45:

55 to 55;

45.

26. The coated stent of claim 15, wherein said plurality of intersections at which portions of the at least one strand overlap with each other are unfixed to one other after forming said first and second dry coatings.

27. The coated stent of claim 15, wherein said at least one strand comprises opposing sets of helical metallic strands.

13-14. -14. (canceled)

19. (canceled)

22-24. -24. (canceled)

25. A method of making a coated stent comprising:

spray coating a first solution comprising a first solvent or solvent mixture onto a tubular metallic body while rotating the tubular metallic body about a longitudinal axis to form a first wet coating;

heating said tubular body after said step of spray coating said first solution onto said tubular body at a temperature and time duration to cause substantially all of said first solvent or solvent mixture to evaporate from said first wet coating, forming a first dry coating;

spray coating a second solution comprising a second solvent or solvent mixture onto said tubular body after forming said first dry coating to form a second wet coating, the second wet coating conformally coating at least a portion of the first dry coating; and

heating said tubular body after said step of spray coating said second solution onto said tubular body at a temperature and time duration to cause substantially all of said second solvent or solvent mixture to evaporate from said second wet coating, forming a second dry coating;

wherein said first and second dry coatings have a combined thickness of less than 50 microns;

wherein the first solution comprises a first set of solids in the first solvent or solvent mixture, said first set of solids comprising 10 to 99 weight percent of poly(L-lactide-co-ε

-caprolactone) (PLCL), 1 to 90 weight percent of poly(L-lactide) (PLA), and 0.1-20 weight percent of paclitaxel; and

wherein the second solution comprises a second set of solids in the second solvent or solvent mixture, said second set of solids comprising 10 to 99 weight percent of PLCL and 1 to 90 weight percent of PLA,said second coating not containing a therapeutic agent.

28. (canceled)

29. The method of C1aim25, wherein said first coating is configured to release said paclitaxel.

30. A coated stent comprising (a) a tubular metallic substrate, (b) a first coating at least partially covering said substrate, said first coating comprising a first biodegradable polymer or blend of biodegradable polymers, and paclitaxel, wherein the amount of paclitaxel in the stent is in the range of from 0.02 to 0.400 ug/mm² of the surface area of the stent, and (c) a second coating at least partially covering said first coating, said second coating comprising a second biodegradable polymer or blend of biodegradable polymers, said second coating not containing a therapeutic agent,

wherein said first biodegradable polymer or blend of biodegradable polymers is the same or different from the second biodegradable polymer or blend of biodegradable polymers;

and

wherein the first coating thickness is from 1 to 15 microns and the second coating thickness is from 1 to 35 microns.