VISUAL INDICATION OF RUPTURE OF DRUG RESERVOIR

• US 20110098640A1
• Filed: 10/22/2010
• Published: 04/28/2011
• Est. Priority Date: 10/22/2009
• Status: Active Grant

• Current Assignee: Microchips Biotech, Inc. (Keratin Biosciences, Inc.)
• Original Assignee: On Demand Therapeutics, Inc.
• Inventors: HORNE, Kenneth N., Scholl, John A., Santini, John T. JR., Spooner, Gregory J.R.
• Granted Patent: US 8,657,804 B2
• Time in Patent Office: Days
• US Class Current: 604/93.01
• CPC Class Codes: A61F 2002/3071 Identification means; Administration of patients
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 2250/0089 coded with symbols, e.g. dots, numbers, letters, words
• CPC Class Codes: A61F 2250/0097 Visible markings, e.g. indicia
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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

Abstract

The present disclosure relates to methods for visualizing the opening of a drug reservoir of an implantable medical device. In particular, the present disclosure provides methods for observing the release or exposure of contents from a drug reservoir of a medical device placed within the vitreous of an eye of a subject. The methods include implanting a drug delivery device within an anatomy of a subject. The drug device includes a plurality of reservoirs, each loaded with a therapeutic agent and a marker. Furthermore, the drug delivery device comprises a plurality of barrier layers for separating the contents of one of the plurality of reservoirs from the anatomy. The method further includes irradiating at least one of the plurality of barrier layers such that at least one of the plurality of reservoirs is breached, thereby triggering release of the therapeutic agent and the marker from the device. By visually detecting release of the marker into the anatomy, release of the therapeutic agent into the anatomy is verified.

Claims

1. A method comprising:

a. implanting a drug delivery device within anatomy of a subject, wherein the drug delivery device comprises;

i. a plurality of reservoirs, each loaded with a therapeutic agent and a marker; and

ii. a plurality of barrier layers, each separating contents of one of said plurality of reservoirs from said anatomy;

b. irradiating at least one of said plurality of barrier layers such that at least one of said plurality of barrier layers is breached, thereby triggering release of said therapeutic agent and said marker from the reservoir of said device; and

c. visually detecting release of said marker into said anatomy in order to verify release of said therapeutic agent into said anatomy.

2. The method of claim 1, wherein said marker is a fluorophore, and wherein said fluorophore is selected from the group consisting of fluorescein, rose Bengal, indocyanine green, and rhodamine.

3. The method of claim 1, wherein said therapeutic agent comprises one or more of the group consisting of anti-inflammatories, anti-infectives, anti-allergens, cholinergic agonists and antagonists, adrenergic agonists and antagonists, anti-glaucoma agents, agents for cataract prevention or treatment, neuroprotection agents, anti-oxidants, antihistamines, anti-platelet agents, anti-coagulants, anti-thrombic agents, anti-scarring agents, anti-proliferatives, anti-tumor agents, complement inhibitors, decongestants, vitamins, growth factors, anti-growth factor agents, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, limus family compounds, and combinations thereof.

4. The method of claim 3, wherein said anti-growth factor agent is an anti-vascular endothelial growth factor (anti-VEGF) agent.

5. The method of claim 4, wherein said anti-VEGF agent is selected from the group consisting of aflibercept (VEGF trap), bevacizumab (AVASTIN), pegaptanib sodium (MACUGEN), and ranibizumab (LUCENTIS).

6. The method of claim 1, wherein said irradiating comprises an application of energy from a laser, wherein the laser is selected from the group consisting of an argon ion laser, a Nd:

YAG laser, a frequency-doubled Nd;

YAG laser, a diode laser, a Nd;

YLF laser, a krypton laser, a dye laser, and a helium-neon laser.

7. The method of claim 1, wherein said implanting comprises placement of said drug delivery device within or adjacent to an ocular region of the subject.

8. The method of claim 1, wherein said implanting comprises intravitreal injection of said device.

9. The method of claim 1, further comprising:

d. distinguishing between an unloaded reservoir and at least one loaded reservoir, wherein the unloaded reservoir is produced due to essentially complete release of said therapeutic agent and said marker, and wherein the at least one loaded reservoir still contains said therapeutic agent and said marker;

e. irradiating at least one of said plurality of barrier layers such that said at least one loaded reservoir is breached, thereby triggering further release of said therapeutic agent and said marker from said device; and

f. visually detecting release of said marker from said loaded reservoir into said anatomy in order to verify further release of said therapeutic agent.

10. The method of claim 9, further comprising repeating steps d-f until all of said plurality of reservoirs are unloaded reservoirs.

11. A method comprising:

a. implanting a drug delivery device within anatomy of a subject, wherein the drug delivery device comprises;

i. a plurality of reservoirs, each loaded with a therapeutic agent; and

ii. a plurality of barrier layers, each separating contents of one of said plurality of reservoirs from said anatomy;

b. irradiating at least one of said plurality of barrier layers such that at least one of said plurality of reservoirs becomes a breached reservoir that generates or exposes a visual indicator, and

c. visually detecting said visual indicator in order to verify exposure of said therapeutic agent to said anatomy.

12. The method of claim 11, wherein said visual indicator comprises an air bubble and said visually detecting is accomplished by use of an ophthalmic slit-lamp microscope.

13. The method of claim 11, wherein said visual indicator comprises a hole in said barrier layer and said visually detecting is accomplished by use of an ophthalmic slit-lamp microscope.

14. The method of claim 11, wherein said visual indicator comprises a predetermined color of said barrier layer, and wherein the predetermined color indicates a ruptured barrier layer.

15. The method of claim 11, wherein said visual indicator is a shape of said barrier layer.

16. The method of claim 11, further comprising:

d. distinguishing between an unloaded reservoir and at least one loaded reservoir, wherein the unloaded reservoir is produced due to essentially complete release of said therapeutic agent, and wherein the at least one loaded reservoir still contains said therapeutic agent;

e. irradiating at least one of said plurality of barrier layers such that said at least one loaded reservoir becomes a breached reservoir that generates or exposes said visual indicator; and

f. visually detecting said visual indicator in order to verify further exposure of said therapeutic agent to said anatomy.

17. The method of claim 16, further comprising repeating steps d-f until all of said plurality of reservoirs are unloaded reservoirs.

18. A drug delivery device for implantation into an eye, the drug delivery device comprising:

a first reservoir configured to be loaded with a first therapeutic agent;

a first marker associated with the first therapeutic agent; and

a barrier layer of the first reservoir, wherein the barrier layer extends circumferentially around the first reservoir, wherein the first reservoir is configured, in response to absorption by a first optical radiation at the barrier layer, to release the first therapeutic agent and the first marker, wherein the first marker indicates the release of the first therapeutic agent.

19. The drug delivery device of claim 18, wherein the drug delivery device is a rod-like structure.

20. The drug delivery device of claim 18, further comprising:

a plurality of reservoirs, wherein each reservoir is configured to be loaded with a therapeutic agent, wherein each reservoir has a barrier layer, wherein each barrier layer extends circumferentially around its respective reservoir, and wherein each reservoir is configured, in response to an optical radiation at its respective barrier layer, to release the therapeutic agent and a marker associated with the therapeutic agent to indicate the release of the therapeutic agent.

21. The drug delivery device of claim 20, wherein each reservoir of the plurality of reservoirs are configured to receive the optical radiation independent of the other reservoirs of the plurality of reservoirs.

22. The drug delivery device of claim 18, further comprising a visual indication associated with the first reservoir for identifying the first reservoir.

23. The drug delivery device of claim 22, wherein the visual indication includes a plurality of markings, wherein each marking is located on the device so that at least one marking is visible by a user of a device applying the optical radiation.

24. The drug delivery device of claim 23, wherein the plurality of marking are circumferentially positioned around the first reservoir.

25. The drug delivery device of claim 18, wherein the drug delivery device is configured to be free-floating within the eye after implantation.