Multi-layer biodegradable device having adjustable drug release profile

• US 9,682,174 B2
• Filed: 02/17/2016
• Issued: 06/20/2017
• Est. Priority Date: 03/11/2013
• Status: Active Grant

• Current Assignee: BioInspire Technologies, Inc.
• Original Assignee: BioInspire Technologies, Inc.
• Inventors: Hakimimehr, Dorna, Hammerick, Kyle
• Primary Examiner(s): Palenik, Jeffrey T
• Application Number:
  US15/046,285
• Publication Number:
  US 20160158419A1
• Time in Patent Office: 489 Days
• Field of Search: None
• CPC Class Codes: A61B 17/24 for use in the oral cavity, larynx, bronchial passages or nose for medical inspection of cavities or tubes in the body A61B1/00; Tongue scrapers
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/61 containing two or more active agents in different layers
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/028 Other inorganic materials not covered by A61L31/022 - A61L31/026
• CPC Class Codes: A61L 31/046 Fibrin; Fibrinogen
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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: 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: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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 9/12 : Antihypertensives
• CPC Class Codes: Y10T 156/10 : Methods of surface bonding and/or assembly therefor

Abstract

Methods and apparatus for a biodegradable multi-layer device suitable for medical applications are provided, wherein the device is formed from multiple film-layers configured to have different characteristics from one another such as different release profiles for therapeutic agents, adhesive properties, stiffness properties, and solubility properties. The film-layers may include a solid fibrinogen component. A device having multiple film-layers may take a non-adherent form during delivery to a target location within or on tissue, and thereafter may be exposed to moisture to take an adherent form on the tissue. The device may include a number of additives, including materials to improve the mechanical properties of the device, or one or more therapeutic or contrast agents.

Claims

1. A method of manufacturing a device, comprising:

forming in vitro a first film-layer from a first composition comprising solid fibrinogen and a first amount of non-aqueous solvent by processing the first composition for a first time interval required to substantially eliminate the first amount of non-aqueous solvent, the first film-layer exhibiting a first characteristic in vivo; and

bonding in vitro a second film-layer to the first film-layer, the second film-layer formed from a second composition comprising solid fibrinogen and a second amount of non-aqueous solvent by processing the second composition for a second time interval required to substantially eliminate the second amount of non-aqueous solvent, the second film-layer exhibiting a second characteristic in vivo,

wherein the first time interval is different from the second time interval and the first characteristic is different from the second characteristic, and the first composition is substantially identical to the second composition, except the first amount of non-aqueous solvent is different from the second amount of non-aqueous solvent.

2. The method of claim 1, wherein bonding the second film-layer to the first film-layer comprises bonding the second film-layer to the first film-layer using an intermediate layer disposed between the first film-layer and the second film-layer.

3. The method of claim 2, wherein the intermediate layer is configured to dissolve to create a reservoir, pores, void, or channel between the first film-layer and the second film-layer.

4. The method of claim 1, wherein the first film-layer further comprises a first therapeutic agent,

wherein the first characteristic is a first release profile for the first therapeutic agent.

5. The method of claim 1, wherein the second film-layer further comprises a second therapeutic agent,

wherein the second characteristic is a second release profile for the second therapeutic agent.

6. The method of claim 5, wherein the first therapeutic agent or the second therapeutic agent or both comprise 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, RNA, or DNA.

7. The method of claim 5, wherein the first therapeutic agent is different from the second therapeutic agent.

8. The method of claim 1, wherein the first characteristic is a first adhesive property of the first film-layer and the second characteristic is a second adhesive property of the second film-layer.

9. The method of claim 1, wherein the first characteristic is a first solubility property of the first film-layer and the second characteristic is a second solubility property of the second film-layer.

10. The method of claim 1, wherein the device is configured to form a fibrin patch upon exposure to moisture.

11. The method of claim 1, wherein processing the first composition comprises drying the first composition.

12. The method of claim 1, wherein the first film-layer or the second film-layer or both further comprise calcium salt, solid thrombin mixed with the solid fibrinogen, a plasticizer, or a contrast agent that renders the device radiopaque, or any combination thereof.

13. The method of claim 1, wherein the first film-layer or the second film-layer or both are coated with a protective layer.

14. The method of claim 1, wherein the first film-layer is bonded to the second composition before the second film-layer is formed.

15. The method of claim 1, wherein bonding the second film-layer to the first film-layer comprises depositing the second film-layer on the first film-layer.

16. The method of claim 1, wherein forming the first film-layer comprises forming the first film-layer from the first composition in a mold.

17. The method of claim 1, wherein the first characteristic is a first surface roughness or texture property of the first film-layer comprising surface projections, perforations, microstructures, nanostructures, ridges, dimples, or any combination thereof, and

wherein the second characteristic is a second surface roughness or texture property of the second film-layer comprising surface projections, perforations, microstructures, nanostructures, ridges, dimples, or any combination thereof.

18. The method of claim 1, wherein the first composition is processed for a first time interval in a first ambient humidity, and the second composition is processed for a second time interval in a second ambient humidity,

wherein the first ambient humidity is different from the second ambient humidity.