Multi-layer biodegradable device having adjustable drug release profile

• US 9,271,925 B2
• Filed: 03/11/2013
• Issued: 03/01/2016
• 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:
  US13/794,355
• Publication Number:
  US 20140255464A1
• Time in Patent Office: 1,086 Days
• Field of Search: None
• US Class Current: 1/1
• 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 device comprising:

a first film-layer comprising fibrinogen,

the first film-layer formed by processing a first composition comprising a first amount of non-aqueous solvent for a first time interval to produce a first characteristic selected from the group consisting of a release profile of one or more therapeutic agents over time, adhesiveness, solubility, matrix stiffness, porosity, and degradation rate of the first film-layer;

optionally, an intermediate layer comprising an adhesive configured to bond to the first and second film-layers; and

the second film-layer optionally bonded to the first film-layer,

the second film-layer comprising fibrinogen,

the second film-layer formed by processing a second composition comprising a second amount of non-aqueous solvent for a second time interval to produce a second characteristic selected from the group consisting of a release profile of one or more therapeutic agents over time, adhesiveness, solubility, matrix stiffness, porosity, and degradation rate of the second film-layer,

wherein the second composition has the same composition as the first composition except the second amount of non-aqueous solvent is different from the first amount of non-aqueous solvent such that the second film-layer has a physical structure sufficient to produce the second characteristic which is different in value from the first characteristic of the first film-layer.

2. The device 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.

3. The device of claim 2, 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.

4. The device of claim 3, 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.

5. The device of claim 3, wherein the first therapeutic agent is different from the second therapeutic agent.

6. The device 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.

7. The device 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.

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

9. The device of claim 1, wherein processing the first composition comprises drying the first composition.

10. The device of claim 1, wherein the first time interval is different from the second time interval.

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

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

13. The device of claim 1, further comprising an intermediate layer disposed between the first film-layer and the second film-layer, the intermediate layer configured to dissolve to create a reservoir, pores, void, or channel between the first film-layer and the second film-layer.

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

15. The device of claim 1, wherein the physical structure is a property of the second film-layer comprising surface projections, perforations, microstructures, nanostructures, ridges, dimples, or any combination thereof.

17. The device of claim 1, wherein the first characteristic and second characteristic are both matrix stiffness.

18. The device of claim 1, wherein processing the first composition comprises exposing the first composition to an atmosphere of lower humidity when compared to the humidity of the atmosphere the second composition is exposed to during processing.

19. The device of claim 1, wherein the non-aqueous solvent comprises ethanol.

20. The device of claim 1, wherein processing the first composition comprises exposing the first composition to a higher air-flow rate when compared to the air flow rate the second composition is exposed to during processing.

16. A device comprising:

a first film-layer comprising fibrinogen,

wherein the first film-layer possesses one or more properties selected from the group consisting of porosity, surface projections, perforations, microstructures, nanostructures, ridges, and dimples sufficient to produce a first characteristic selected from the group consisting of a release profile of one or more therapeutic agents over time, adhesiveness, matrix stiffness, porosity, and degradation rate, the first film-layer formed from a first amount of non-aqueous solvent;

optionally, an intermediate layer comprising an adhesive configured to bond to the first film-layer and a second film-layer, and

the second film-layer, optionally bonded to the first film-layer, the second film-layer comprising fibrinogen,

wherein the second film-layer has the physical structure sufficient to produce a second characteristic which is different in value from the first characteristic of the first film-layer, the second characteristic is selected from the group consisting of a release profile of one or more therapeutic agents over time, adhesiveness, matrix stiffness, porosity, and degradation rate, the second film-layer formed from a second amount of non-aqueous solvent; and

wherein the first and second film-layers are formed from the same composition except the first amount of non-aqueous solvent is different from the second amount of non-aqueous solvent.