Implantable scaffolds for treatment of sinusitis

• US 10,232,082 B2
• Filed: 04/20/2017
• Issued: 03/19/2019
• Est. Priority Date: 06/29/2015
• Status: Active Grant

• Current Assignee: Lyra Therapeutics, Inc.
• Original Assignee: 480 Biomedical, Inc.
• Inventors: You, Changcheng, Pham, Quynh, Concagh, Danny
• Primary Examiner(s): Prebilic, Paul B
• Application Number:
  US15/492,103
• Publication Number:
  US 20170224476A1
• Time in Patent Office: 698 Days
• CPC Class Codes: A61F 2/186 Nose parts
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0031 made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• 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 2210/0681 Sinus (maxillaris)
• 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 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: C08L 67/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence

Abstract

This disclosure describes, inter alia, materials, devices, kits and methods that may be used to treat chronic sinusitis. More specifically, a drug-eluting scaffold is implanted in the middle meatus to treat chronic sinusitis for weeks to months.

Claims

1. A method of treatment, comprising delivering an expandable scaffold comprising a therapeutic agent to a sinus cavity of a human patient, wherein the scaffold self-expands to a first width within the sinus cavity upon delivery and wherein the scaffold further expands over time to a second width in vivo as the surrounding sinus cavity enlarges such that the scaffold remains in contact with the sinus cavity, and wherein the expandable scaffold is one for which, when submersed in a pH 7.4 PBS buffer solution containing 2 wt % SDS at 37°

C. under gentle shaking on a rotary shaker and the buffer solution is removed completely on a weekly basis as a sample for therapeutic agent quantification and replaced with fresh buffer,

(a) a quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 1% to 10%, beginning with the second week sample and extending up to the twelfth week sample, or

(b) a quantity of therapeutic agent released per unit scaffold area in each sample, beginning with the second week sample and extending up to the twelfth week sample, ranges from 0.05 to 4 μ

g/mm²/week, where scaffold area is equal to π

DL, where D is the manufactured diameter of the scaffold and L is the manufactured length of the scaffold, or

(c) both (a) and (b).

2. The method of claim 1, wherein an absolute quantity of therapeutic agent released in each sample does not vary by more than 33% between any two samples, beginning with the second week sample and extending up to the twelfth week sample.

3. The method of claim 1, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 1% to 10%, beginning with the second week sample and extending up to the twelfth week sample.

4. The method of claim 1, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 5% to 9%, beginning with the second week sample and extending up to the twelfth week sample.

5. The method of claim 1, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 6% to 8%, beginning with the second week sample and extending up to the twelfth week sample.

6. The method of claim 1, wherein the quantity of therapeutic agent released per unit scaffold area in each sample, beginning with the second week sample and extending up to the twelfth week sample, ranges from 0.05 to 4 μ

g/mm²/week.

7. The method of claim 1, wherein the quantity of therapeutic agent released per unit scaffold area in each sample, beginning with the second week sample and extending up to the twelfth week sample, ranges from 0.1 to 1 μ

g/mm²/week.

8. The method of claim 1, wherein the therapeutic agent is mometasone furoate.

9. The method of claim 1, wherein the expandable scaffold comprises (a) a plurality of braided polymeric strands that comprise a biodegradable polymer and (b) a therapeutic agent-containing layer over the braided polymeric strands that comprises the therapeutic agent.

10. The method of claim 9, wherein the braided polymeric strands comprise poly(lactide-co-glycolide).

11. The method of claim 9, wherein the braided polymeric strands comprise poly(lactide-co-glycolide) having a molar percentage of lactide ranging from 82% to 87% and a molar percentage of glycolide ranging from 13% to 18%.

12. The method of claim 9, wherein the therapeutic-agent-containing layer comprises poly(lactic acid-co-caprolactone).

13. The method of claim 9, wherein the therapeutic-agent-containing layer comprises poly(lactic acid-co-caprolactone) and mometasone furoate.

14. The method of claim 9, wherein the expandable scaffold further comprising a topcoat layer over the therapeutic-agent-containing layer that comprises a blend of poly(lactic acid-co-caprolactone) and polylactic acid.

15. The method of claim 14, wherein poly(lactide-co-caprolactone) in each of the therapeutic-agent-containing layer and the topcoat layer has a molar percentage of lactide ranging from 60% to 80% and a molar percentage of caprolactone ranging from 20% to 40%.

16. The method of claim 14, wherein poly(lactide-co-caprolactone) in each of the therapeutic-agent-containing layer and the topcoat layer has a molar percentage of lactide ranging from 65% to 75% and a molar percentage of caprolactone ranging from 25% to 35%.

17. The method of claim 14, wherein the blend comprises from 60 to 80 wt % poly(lactic acid-co-caprolactone) and from 20 to 40 wt % polylactic acid.

18. The method of claim 14, wherein the blend comprises from 70 to 80 wt % poly(lactic acid-co-caprolactone) and from 20 to 30 wt % polylactic acid.

19. The method of claim 14, wherein poly(lactide-co-caprolactone) in each of the therapeutic-agent-containing layer and the topcoat layer has a molar percentage of lactide ranging from 60 to 80% and a molar percentage of caprolactone ranging from 20 to 40%, and wherein the blend comprises from 70 to 80 wt % poly(lactic acid-co-caprolactone) and from 20 to 30 wt % polylactic acid.

20. The method of claim 9, wherein the therapeutic-agent-containing layer comprises between 5 wt % and 50 wt % mometasone furoate.

21. The method of claim 9, wherein the therapeutic-agent-containing layer comprises between 20 wt % and 40 wt % mometasone furoate.

22. The method of claim 14, wherein the therapeutic-agent-containing layer ranges from 10 to 20 μ

m in thickness and the topcoat layer ranges from 1 to 5 μ

m in thickness.

23. The method of claim 14, wherein the therapeutic-agent-containing layer ranges from 10 to 16 μ

m in thickness and the topcoat layer ranges from 1.2 to 2 μ

m in thickness.

24. The method of claim 9, wherein the expandable scaffold further comprises a support coating disposed over the braided polymeric strands and under the therapeutic agent-containing layer.

25. The method of claim 24, wherein the support coating comprises crosslinked poly(lactide-co-caprolactone).

26. The method of claim 24, wherein the support coating comprises crosslinked poly(lactide-co-caprolactone) having a molar percentage of lactide ranging from 30% to 50% and a molar percentage of caprolactone ranging from 50% to 70%.

27. The method of claim 24, wherein the support coating comprises an isocyanate-crosslinked poly(lactide-co-caprolactone).

28. The method of claim 25, wherein to poly(lactide-co-caprolactone) in the support coating is crosslinked with hexamethylene diisocyanate.

29. The method of claim 1, wherein the second width is 125% of the first width.

30. The method of claim 1, wherein the second width is 150% of the first width.

31. The method of claim 1, wherein the scaffold further expands to the second width over a period of 13 weeks.

32. The method of claim 1, wherein the scaffold further expands to the second width over a period of 26 weeks.

33. The method of claim 1, wherein the scaffold is implanted into a human middle meatus.

34. The method of claim 1, wherein the expandable scaffold is delivered to the native middle meatus using a 2 to 4 mm catheter.

35. The method of claim 1, wherein the expandable scaffold has an unconstrained diameter ranging from 5 to 25 mm at the time of delivery.

36. The method of claim 1, wherein the expandable scaffold has an unconstrained diameter ranging from 9 to 15 mm at the time of delivery.

37. The method of claim 1, wherein the expandable scaffold is selected from the group consisting of an expandable scaffold ranging from 5 to 8 mm in unconstrained diameter at the time of delivery, an expandable scaffold ranging from 7 to 12 mm in unconstrained diameter at the time of delivery, an expandable scaffold ranging from 10 to 15 mm in unconstrained diameter at the time of delivery, an expandable scaffold ranging from 13 to 20 mm in unconstrained diameter at the time of delivery, and an expandable scaffold ranging from 17 to 25 mm in unconstrained diameter at the time of delivery.

38. The method of claim 1, wherein the therapeutic agent is mometasone furoate, and wherein a quantity of mometasone furoate initially present in the scaffold per unit scaffold area ranges from 0.1 μ

g/mm² to 20 μ

g/mm².

39. A method of treatment, comprising delivering an expandable scaffold comprising a therapeutic agent into the middle meatus of a human patient, wherein the scaffold self-expands to a first width within the middle meatus upon delivery and wherein the scaffold further expands over time to a second width in vivo as the middle meatus enlarges such that the scaffold remains in contact with the middle meatus, and wherein the expandable scaffold is one for which, when submersed in a pH 7.4 PBS buffer solution containing 2 wt % SDS at 37°

C. under gentle shaking on a rotary shaker and the buffer solution is removed completely on a weekly basis as a sample for therapeutic agent quantification and replaced with fresh buffer,

(a) a quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 1% to 10%, beginning with the second week sample and extending up to the twelfth week sample, or

(b) a quantity of therapeutic agent released per unit scaffold area in each sample, beginning with the second week sample and extending up to the twelfth week sample, ranges from 0.05 to 4 μ

g/mm²/week, where scaffold area is equal to π

DL, where D is the manufactured diameter of the scaffold and L is the manufactured length of the scaffold, or

(c) both (a) and (b).

40. The method of claim 39, wherein the expandable scaffold is delivered to the native middle meatus using a 2 to 4 mm catheter.

41. The method of claim 39, wherein an absolute quantity of therapeutic agent released in each sample does not vary by more than 33% between any two samples, beginning with the second week sample and extending up to the twelfth week sample.

42. The method of claim 39, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 1% to 10%, beginning with the second week sample and extending up to the twelfth week sample.

43. The method of claim 39, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 5% to 9%, beginning with the second week sample and extending up to the twelfth week sample.

44. The method of claim 39, wherein the quantity of therapeutic agent released in each sample, relative to a total amount of therapeutic agent originally in the scaffold, ranges from 6% to 8%, beginning with the second week sample and extending up to the twelfth week sample.

45. The method of claim 39, wherein the therapeutic agent is mometasone furoate.

46. The method of claim 39, wherein the expandable scaffold comprises (a) a plurality of braided polymeric strands that comprise a biodegradable polymer and (b) a therapeutic agent-containing layer over the braided polymeric strands that comprises the therapeutic agent.

47. The method of claim 46, wherein the braided polymeric strands comprise poly(lactide-co-glycolide).