Drug delivery methods, structures, and compositions for nasolacrimal system

• US 9,610,194 B2
• Filed: 02/14/2014
• Issued: 04/04/2017
• Est. Priority Date: 03/31/2006
• Status: Active Grant

• Current Assignee: Mati Therapeutics, Inc
• Original Assignee: Mati Therapeutics, Inc
• Inventors: De Juan, Jr., Eugene, Gifford, III, Hanson S., Boyd, Stephen, Deem, Mark, Reich, Cary J.
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US14/180,592
• Publication Number:
  US 20140161863A1
• Time in Patent Office: 1,145 Days
• Field of Search: None
• CPC Class Codes: A61F 2220/0008 Fixation appliances for connecting prostheses to the body
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0087 colour-coded
• 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: A61F 9/00772 Apparatus for restoration of tear ducts
• CPC Class Codes: A61F 9/00781 Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment drainage implants in general A61M27/002
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61K 9/0017 Non-human animal skin, e.g. pour-on, spot-on
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• 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 31/04 : Antibacterial agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

A drug insert is configured for use with an implant. The implant is configured for insertion into a lacrimal canaliculus. The drug insert includes a drug core comprising a therapeutic agent and a polymer; and a sheath body comprising material substantially impermeable to the therapeutic agent, wherein the drug core is positioned within the sheath body. The sheath body is configured to provide an exposed end of the drug core that releases therapeutic agent to an eye when the drug insert is disposed within the implant and the implant is positioned in the lacrimal canaliculus. A distal end of the drug core is sealed with a medical-grade adhesive.

Claims

1. A method for delivering a therapeutic agent to an eye comprising:

placing a punctal plug into a lacrimal canaliculus of a patient, wherein the punctal plug comprises;

a silicone plug body comprising a drug insert;

the drug insert comprising;

a drug core comprising a therapeutic agent contained in a matrix, and

an impermeable sheath body partially covering the drug core,

wherein when the punctal plug is inserted into the lacrimal canaliculus of the patient an exposed surface of the drug core is in direct contact with tear fluid to permit diffusion of the therapeutic agent into the tear fluid of the eye of the patient.

2. The method of claim 1, wherein the sheath body is comprised of at least one of polyimide or polyethylene terephthalate.

3. The method of claim 1, wherein the therapeutic agent comprises a prostaglandin analogue.

4. The method of claim 3, wherein the prostaglandin analogue is selected from the group consisting of latanoprost, bimatoprost, and travoprost.

5. The method of claim 1, wherein the therapeutic agent is a thrombin inhibitor, anti-glaucoma medication, a non-steroidal anti-inflammatory drug (NSAID), a fibrinolytic agent, a vasospasm inhibitor, a vasodilator, an antimicrobial agents, an antifungal, an antiviral, an anticancer chemotherapeutic agent, an anti-inflammatory agent, a hormonal agent, an immunosuppressive agent, a growth hormone antagonist, a growth factor, an angiogenesis inhibitor, a lubricant, a surfactant, a peptide, a protein, or an enzymes.

6. The method of claim 5, wherein the therapeutic agent is dexamethasone, diclofenac, or a peptide.

7. The method of claim 1, wherein the drug core comprises inclusions of the therapeutic agent contained in the matrix.

8. The method of claim 1, wherein the matrix comprises a non-biodegradable polymer.

9. The method of claim 8, wherein the non-biodegradable polymer is selected from the group consisting of silicone, an acrylate, a polyethylene, polyurethane, and polyester.

10. The method of claim 1, wherein the drug core comprises a silicone matrix.

11. The method of claim 1, wherein the drug core comprises a biodegradeable polymer matrix.

12. The method of claim 11, wherein the biodegradable polymer is selected from protein, hydrogel, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lactic acid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymers, modified cellulose, collagen, polyorthoesters, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxy acid) and combinations thereof.

13. The method of claim 1, wherein the drug insert is further configured to release the therapeutic agent for at least 21 days.

14. The method of claim 11, wherein the therapeutic agent treats glaucoma, post-surgical inflammation, dry eye, post-surgical pain, infection, or allergies.

15. A method for delivering a therapeutic agent to an eye comprising:

placing a punctal plug into a lacrimal canaliculus of a patient, wherein the punctal plug comprises;

a silicone plug body comprising a drug insert;

the drug insert comprising;

a drug core comprising a therapeutic agent contained in a matrix, wherein the therapeutic agent is selected from a prostaglandin analogue, a non-steroidal anti-inflammatory drug (NSAID), an anti-inflammatory agent or a an immunosuppressive agent, and

an impermeable sheath body partially covering the drug core,

wherein when the punctal plug is inserted into the lacrimal canaliculus of the patient an exposed surface of the drug core is in direct contact with tear fluid to permit diffusion of the therapeutic agent into the tear fluid of the eye of the patient.

16. The method of claim 15, wherein the prostaglandin analogue is selected from the group consisting of latanoprost, bimatoprost, and travoprost.

17. The method of claim 15, wherein the therapeutic agent is dexamethasone, diclofenac, or a peptide.

18. The method of claim 15, wherein the matrix comprises a non-biodegradable polymer selected from the group consisting of silicone, an acrylate, a polyethylene, polyurethane, and polyester.

19. The method of claim 15, wherein the therapeutic agent treats glaucoma, post-surgical inflammation, dry eye, post-surgical pain, infection, or allergies.

20. The method of claim 15, wherein the drug insert is further configured to release the therapeutic agent for at least 21 days.