APPARATUS AND METHODS FOR DELIVERING THERAPEUTIC AGENTS

• US 20090240215A1
• Filed: 12/19/2008
• Published: 09/24/2009
• Est. Priority Date: 12/20/2007
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Humayun, Mark, Caffey, Sean
• Granted Patent: US 9,308,124 B2
• Time in Patent Office: Days
• US Class Current: 604/290
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/0026 Ophthalmic product dispenser attachments to facilitate positioning near the eye
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• 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 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

In various embodiments, a drug-delivery device includes one or more reservoirs that may each contain a therapeutic agent for delivery to a patient.

Claims

1. A drug-delivery device, comprising:

a first reservoir for containing a first liquid that comprises or consists essentially of a first therapeutic agent;

a second reservoir for containing a second liquid that comprises or consists essentially of a second therapeutic agent different from the first therapeutic agent; and

at least one cannula, in fluid communication with the first and second reservoirs, for separately delivering the first and second liquids to a patient.

2. The drug-delivery device of claim 1, wherein the first reservoir comprises the first liquid and wherein the second reservoir comprises the second liquid.

3. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents treats at least one of glaucoma or ocular hypertension.

4. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of acetazolamide, betaxolol, bimatoprost, brimonidine, brinzolamide, carbidopa, carteolol, dorzolamide, epinephrine, latanoprost, levodopa, levobunolol, levobetaxolol, loratadine, metipranolol, pilocarpine, pseudoephedrine, timolol, travoprost, and unoprostone isopropyl.

5. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents treats at least one of age-related macular degeneration, macular edema associated with diabetic retinopathy, or macular edema associated with retinovascular occlusive diseases.

6. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of ranibizumab, pegaptanib, verteporfin, bevacizumab, a steroid, a drug that prevents beta amyloid deposition in the retina, an anti-human complement activation blocker that blocks complement H activation in the eye, and siRNA molecules.

7. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents treats cytomegalovirus retinitis.

8. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of valganciclovir, vitravene, and cidofovir.

9. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents treats itching and allergic conjunctivitis.

10. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of loteprednol etabonate, naphazoline, pheniramine maleate, pemirolast, and ketotifen fumarate.

11. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents treats at least one of recurrent malignant glioma or malignant brain tumors.

12. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of bevacizumab, irinotecan, and a steroid.

13. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents suppresses an inflammatory reaction.

14. The drug-delivery device of claim 2, wherein the first therapeutic agent is a steroid and the second therapeutic agent is selected from the group consisting of a non-steroidal drug and an anti-cancer drug.

15. The drug-delivery device of claim 2, wherein each of the first and second therapeutic agents provides neuroprotection for at least one of a retinal disease, glaucoma, or a brain disorder.

16. The drug-deliver device of claim 2, wherein each of the first and second therapeutic agents is selected from the group consisting of brain derived growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, nerve growth factor, and tumor necrosis growth factor inhibitor.

17. The drug-delivery device of claim 2, wherein the first and second therapeutic agents treat two different maladies selected from the group consisting of glaucoma, ocular hypertension, age-related macular degeneration, macular edema associated with diabetic retinopathy, macular edema associated with retinovascular occlusive diseases, low tear production, cytomegalovirus retinitis, bacterial conjunctivitis, itching and allergic conjunctivitis, post-operative eye inflammation, inflammation of the cornea due to herpes simplex virus, postoperative inflammation after cataract extraction, corneal ulcers, and Sjö

gren'"'"'s syndrome.

18. The drug-delivery device of claim 2, wherein the first and second therapeutic agents treat two different maladies selected from the group consisting of recurrent malignant glioma, a malignant brain tumor, alzheimers, cerebral edema, and an inflammatory reaction.

19. The drug-delivery device of claim 1, wherein the at least one cannula comprises a first cannula in fluid communication with the first reservoir and a second, separate cannula in fluid communication with the second reservoir.

20. A drug-delivery device, comprising:

a first reservoir for containing a first liquid that comprises or consists essentially of a first therapeutic agent;

a second reservoir for containing a second liquid that comprises or consists essentially of a second therapeutic agent different from the first therapeutic agent;

memory for storing a drug-delivery regimen; and

a microprocessor for controlling a delivery of the first and second liquids to a patient through at least one cannula based on an execution of the stored drug-delivery regimen.

21. The drug-delivery device of claim 20 further comprising a sensor for receiving feedback from the patient.

22. The drug-delivery device of claim 21, wherein the microprocessor modifies the drug-delivery regimen based on the feedback.

23. The drug-delivery device of claim 21, wherein the feedback comprises at least one of a measured eye pressure for the patient, a position of the patient, an activity being undertaken by the patient, or a measured residual amount of the first or second therapeutic agent present in a patient'"'"'s tissue.

24. The drug-delivery device of claim 20, wherein execution of the drug-delivery regimen is impacted by at least one variable selected from the group consisting of the time of day, a patient-specific factor, and identities of the first and second therapeutic agents.

25. The drug-delivery device of claim 20 further comprising a receiver for receiving wireless instructions that reprogram the drug-delivery regimen.

26. A drug-delivery device, comprising:

a reservoir containing a liquid that comprises a therapeutic agent selected from the group consisting of acetazolamide, betaxolol, bevacizumab, bimatoprost, brimonidine, brinzolamide, carbidopa, carteolol, cidofovir, cyclosporine, dorzolamide, epinephrine, a growth factor, irinotecan, ketorolac tromethamine, ketotifen fumarate, latanoprost, levobetaxolol, levobunolol, levodopa, levofloxacin, loratadine, loteprednol etabonate, metipranolol, naphazoline, ofloxacin, pegaptanib, pemirolast, pheniramine maleate, pilocarpine, pseudoephedrine, ranibizumab, a steroid, timolol, travoprost, trifluridine, tumor necrosis factor blocker, unoprostone isopropyl, valganciclovir, verteporfin, vitravene, a drug that prevents beta amyloid deposition in the retina, a drug that prevents beta amyloid deposition in the brain, an anti-human complement activation blocker that blocks complement H activation in the eye, and siRNA molecules; and

a cannula in fluid communication with the reservoir, the cannula having an outlet for delivering the therapeutic agent to a patient.

27. A method for treating an ophthalmic condition, comprising:

a) providing a drug-delivery device comprising;

i) a first reservoir;

ii) a second reservoir; and

iii) at least one cannula, in fluid communication with the first and second reservoirs, the at least one cannula having an outlet;

b) attaching the drug-delivery device onto the conjunctiva of a patient'"'"'s eye such that the outlet of the at least one cannula penetrates the conjunctiva;

c) filling the first reservoir with a first liquid that comprises or consists essentially of a first therapeutic agent;

d) filling the second reservoir with a second liquid that comprises or consists essentially of a second therapeutic agent, the second therapeutic agent being different from the first therapeutic agent; and

e) separately delivering the first and second therapeutic agents to the patient via the outlet of the at least one cannula.

28. The method of claim 27, wherein each of the first and second therapeutic agents treats at least one of glaucoma or ocular hypertension.

29. The method of claim 27, wherein each of the first and second therapeutic agents is selected from the group consisting of acetazolamide, betaxolol, bimatoprost, brimonidine, brinzolamide, carbidopa, carteolol, dorzolamide, epinephrine, latanoprost, levodopa, levobunolol, levobetaxolol, loratadine, metipranolol, pilocarpine, pseudoephedrine, timolol, travoprost, and unoprostone isopropyl.

30. The method of claim 27, wherein each of the first and second therapeutic agents treats at least one of age-related macular degeneration, macular edema associated with diabetic retinopathy, or macular edema associated with retinovascular occlusive diseases.

31. The method of claim 27, wherein each of the first and second therapeutic agents is selected from the group consisting of ranibizumab, pegaptanib, verteporfin, bevacizumab, a steroid, a drug that prevents beta amyloid deposition in the retina, an anti-human complement activation blocker that blocks complement H activation in the eye, and siRNA molecules.

32. The method of claim 27, wherein each of the first and second therapeutic agents treats cytomegalovirus retinitis.

33. The method of claim 27, wherein each of the first and second therapeutic agents is selected from the group consisting of valganciclovir, vitravene, and cidofovir.

34. The method of claim 27, wherein each of the first and second therapeutic agents treats itching and allergic conjunctivitis.

35. The method of claim 27, wherein each of the first and second therapeutic agents is selected from the group consisting of loteprednol etabonate, naphazoline, pheniramine maleate, pemirolast, and ketotifen fumarate.

36. The method of claim 27, wherein the first and second therapeutic agents treat two different maladies selected from the group consisting of glaucoma, ocular hypertension, age-related macular degeneration, macular edema associated with diabetic retinopathy, macular edema associated with retinovascular occlusive diseases, low tear production, cytomegalovirus retinitis, bacterial conjunctivitis, itching and allergic conjunctivitis, post-operative eye inflammation, inflammation of the cornea due to herpes simplex virus, postoperative inflammation after cataract extraction, corneal ulcers, and Sjö

gren'"'"'s syndrome.

37. The method of claim 27, wherein the at least one cannula comprises a first cannula in fluid communication with the first reservoir and a second, separate cannula in fluid communication with the second reservoir.

38. A method for treating an ophthalmic condition, comprising:

implanting a drug-delivery device in a patient'"'"'s eye; and

filling the drug-delivery device with a liquid that comprises a therapeutic agent selected from the group consisting of acetazolamide, betaxolol, bevacizumab, bimatoprost, brimonidine, brinzolamide, carbidopa, carteolol, cidofovir, cyclosporine, dorzolamide, epinephrine, ketorolac tromethamine, ketotifen fumarate, latanoprost, levobetaxolol, levobunolol, levodopa, levofloxacin, loratadine, loteprednol etabonate, metipranolol, naphazoline, ofloxacin, pegaptanib, pemirolast, pheniramine maleate, pilocarpine, pseudoephedrine, ranibizumab, a steroid, timolol, travoprost, trifluridine, unoprostone isopropyl, valganciclovir, verteporfin, vitravene, a drug that prevents beta amyloid deposition in the retina, an anti-human complement activation blocker that blocks complement H activation in the eye, and siRNA molecules.

39. A method for treating a cancerous condition, comprising:

implanting a drug-delivery device near a patient'"'"'s tumor; and

filling the drug-delivery device with a combination of drugs selected from the group consisting of i) bevacizumab and CPT-11;

ii) ranibizumab and CPT-11;

iii) letrozole and tamoxifen;

iv) doxorubicin and docetaxel;

v) bevacizumab and any chemotherapy drug;

vi) gemcitabine and CP-870,893;

vii) PF-3512676 and a cytotoxic chemotherapy drug;

viii) bevacizumab and paclitaxel;

ix) docetaxel and sunitinib;

x) bevacizumab and sunitinib;

xi) lapatinib and letrozole;

xii) ixabepilone and capecitabine; and

xiii) paclitaxel protein-bound and a taxane.