Visual indication of rupture of drug reservoir

• US 8,657,804 B2
• Filed: 10/22/2010
• Issued: 02/25/2014
• Est. Priority Date: 10/22/2009
• Status: Expired due to Fees

• 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.
• Primary Examiner(s): Desanto, Matthew F
• Application Number:
  US12/910,572
• Publication Number:
  US 20110098640A1
• Time in Patent Office: 1,222 Days
• Field of Search: 600473-480, 600/407, 604/264, 604/290, 604/521, 6048901-8921
• US Class Current: 604/521
• 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 or adjacent to an ocular region 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 the plurality of reservoirs from the ocular region;

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

c. visibly observing release of the marker into the ocular region with visible light in order to verify exposure of the therapeutic agent to the ocular region.

2. The method of claim 1, wherein the 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.

3. The method of claim 2, wherein the anti growth factor agent is an anti-vascular endothelial growth factor (anti-VEGF) agent.

4. The method of claim 3, wherein the anti-VEGF agent is selected from the group consisting of aflibercept (VEGF trap), bevacizumab (AVASTIN), pegaptanib sodium (MACUGEN), and ranibizurnab (LUCENTIS).

5. 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 the therapeutic agent and the marker, and wherein the at least one loaded reservoir still contains additional therapeutic agent and additional marker;

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

f. visibly observing release of the additional marker from the loaded reservoir into the ocular region with visible light in order to verify exposure of the additional therapeutic agent to the ocular region.

6. The method of claim 5, further comprising repeating steps d-f until all of the plurality of reservoirs are unloaded reservoirs.

7. The method of claim 1, wherein release of the marker from the reservoir into the ocular region occurs prior to release of the therapeutic agent from the reservoir into the ocular region.

8. The method of claim 7, wherein visibly observing release of the marker from the reservoir into the ocular region occurs prior to release of the therapeutic agent from the reservoir into the ocular region.

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

10. The method of claim 1, wherein the 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.

11. The method of claim 1, wherein the ocular region comprises a sclera, a cornea, a choroid, a retina, a vitreous body, a pars plana, or a conjunctiva.

12. The method of claim 1, wherein the implanting comprises intravitreal injection or insertion of the device.

13. The method of claim 1, wherein the marker is unbound from the therapeutic agent.

14. The method of claim 1, wherein the marker comprises a coating on an internal surface of the reservoir.

15. The method of claim 1, wherein the drug delivery device further comprises a second marker arranged spatially in the reservoir with the therapeutic agent and the marker, the method further comprising visibly observing release of the second marker into the ocular region with visible light in order to verify complete release of the therapeutic agent into the ocular region.

16. A method comprising:

a. implanting a drug delivery device within or adjacent to an ocular region 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 the plurality of reservoirs from the ocular region;

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

c. visibly observing the visual indicator with visible light in order to verify exposure of the therapeutic agent to the ocular region.

17. The method of claim 16, 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 the therapeutic agent, and wherein the at least one loaded reservoir still contains the therapeutic agent;

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

f. visibly observing the visual indicator with visible light in order to verify further exposure of the therapeutic agent to the ocular region.

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

19. The method of claim 16, wherein the visual indicator comprises an air bubble and the visually detecting with visible light is accomplished by use of an ophthalmic slit-lamp microscope.

20. The method of claim 16, wherein the visual indicator comprises a hole in the barrier layer and the visually detecting with visible light is accomplished by use of an ophthalmic slit-lamp microscope.

21. The method of claim 16, wherein the visual indicator comprises a predetermined color of the barrier layer, and wherein the predetermined color indicates a ruptured barrier layer.

22. The method of claim 16, wherein the visual indicator is a shape of the barrier layer.