Free-standing biodegradable patch

• US 9,072,681 B2
• Filed: 10/15/2013
• Issued: 07/07/2015
• Est. Priority Date: 09/18/2009
• Status: Active Grant

• Current Assignee: BioInspire Technologies, Inc.
• Original Assignee: BioInspire Technologies, Inc.
• Inventors: Hakimimehr, Dorna, Bonan, Raoul
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): MERCIER, MELISSA S
• Application Number:
  US14/054,653
• Publication Number:
  US 20140046255A1
• Time in Patent Office: 630 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 38/4833 Thrombin (3.4.21.5)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61K 9/7046 the adhesive comprising macromolecular compounds
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/046 Fibrin; Fibrinogen
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/141 Plasticizers
• 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: A61L 31/18 Materials at least partially X-ray or laser opaque
• 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: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C12Y 304/21005 : Thrombin (3.4.21.5)

Abstract

Methods and apparatus for a free-standing biodegradable patch suitable for medical applications, especially intravascular, minimally-invasive and intraoperative surgical applications are provided, wherein the patch comprises a free-standing film or device having a mixture of a solid fibrinogen component and a solid thrombin component that, when exposed to an aqueous environment, undergoes polymerization to form fibrin. In alternative embodiments the patch may comprise a solid fibrinogen component, with or without an inorganic calcium salt component. The patch may take a non-adherent form during delivery to a target location within a vessel or tissue, and thereafter may be activated to adhere to vessel wall or tissue, and may include a number of additives, including materials to improve the mechanical properties of the patch, or one or more therapeutic or contrast agents.

Claims

1. A device comprising:

a film comprising solid fibrinogen and a plasticizer that comprises about 5 to about 30 weight percent polyethylene glycol,

wherein the film is free-standing without a support structure and the solid fibrinogen is within the free-standing film.

2. The device of claim 1, wherein the solid fibrinogen is prepared from unsalted fibrinogen.

3. The device of claim 1, wherein the film further comprises calcium salt.

4. The device of claim 1, wherein the film further comprises solid thrombin mixed with the solid fibrinogen.

5. The device of claim 1, wherein the film further comprises a therapeutic agent, and wherein the film is configured to release the therapeutic agent.

6. The device of claim 5, wherein the therapeutic agent comprises one or more anti-inflammatory agents, anti-allergenic agents, anti-bacterial agents, anti-viral agents, anticholinergic agents, antihistamines, antithrombotic agents, anti-scarring agents, antiproliferative agents, antihypertensive agents, anti-restenosis agents, healing promoting agents, vitamins, proteins, genes, growth factors, cells or DNA.

7. The device of claim 1, wherein the polyethylene glycol comprises PEG 400, PEG 1500, PEG 3000, or PEG 6000.

8. The device of claim 1, wherein the film further comprises a contrast agent that renders the device radiopaque.

9. The device of claim 8, wherein the contrast agent is concentrated in a marker band region comprised of a mixture of solid fibrinogen and solid thrombin.

10. The device of claim 1, wherein the film is coated with a water-soluble protective layer.

11. The device of claim 1, wherein the film further comprises a layer of solid thrombin.

12. The device of claim 1, wherein the device comprises a patch.

13. The device of claim 1, wherein the film is adherent prior to exposure to moisture.

14. A system for delivering a tissue or vessel patch, the system comprising:

a delivery device having an expandable member; and

a device of claim 1,

wherein the film is disposed upon and delivered by the expandable member.

15. The system of claim 14, wherein the expandable member is a balloon.

16. The system of claim 15, wherein the film is temporarily affixed to the expandable member by a water-soluble material.

17. The system of claim 16, wherein the water-soluble material comprises polyethylene glycol or polyvinyl pyrrolidone.

18. The system of claim 14, wherein the delivery device further comprises a retractable sheath.

19. The system of claim 14, wherein the film further comprises a therapeutic agent, and wherein the adherent patch is configured to release the therapeutic agent.

20. The system of claim 19, wherein the therapeutic agent comprises one or more anti-inflammatory agents, anti-allergenic agents, anti-bacterial agents, anti-viral agents, anticholinergic agents, antihistamines, antithrombotic agents, anti-scarring agents, antiproliferative agents, antihypertensive agents, anti-restenosis agents, healing promoting agents, vitamins, proteins, genes, growth factors, cells or DNA.

22. The device of claim 3, wherein the calcium salt comprises calcium chloride.

23. The device of claim 1, wherein the film comprises two layers, one layer being an adhesive layer.

24. The device of claim 1, wherein the film has a thickness between 30-500 μ

m.

25. The device of claim 5, wherein the therapeutic agent comprises a steroidal anti-inflammatory agent comprising at least one of 21 acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, triamcinolone hexacetonide, any of their derivatives, and combinations thereof.

26. The device of claim 5, wherein the therapeutic agent comprises fluticasone propionate.

27. The device of claim 1, wherein the film is formed with a color suspension.

28. The device of claim 1, wherein the film is configured for delivery to a vessel, esophagus, stomach, intestine, bronchus, trachea, urethra, ureter, sinus, ear, or heart.

21. A device comprising:

a film comprising solid fibrinogen,

wherein the film is free-standing without a support structure and the solid fibrinogen is within the free-standing film, and

wherein the film further comprises a contrast agent that renders the device radiopaque.