Drug delivery methods, structures, and compositions for nasolacrimal system

• US 8,795,711 B2
• Filed: 04/02/2007
• Issued: 08/05/2014
• Est. Priority Date: 03/31/2006
• Status: Active Grant

• Current Assignee: Mati Therapeutics, Inc
• Original Assignee: Mati Therapeutics, Inc
• Inventors: de Juan, Eugene Jr., Reich, Cary, Boyd, Stephen, Gifford, Hanson G. III, Deem, Mark
• Primary Examiner(s): Switzer, Juliet
• Assistant Examiner(s): HELM, CARALYNNE E
• Application Number:
  US11/695,537
• Publication Number:
  US 20070269487A1
• Time in Patent Office: 2,682 Days
• Field of Search: None
• US Class Current: 424/427
• 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

An implant for insertion into a punctum of a patient comprises a body. The body has a distal end, a proximal end, and an axis therebetween. The distal end of the body is insertable distally through the punctum into the canalicular lumen. The body comprises a therapeutic agent included within an agent matrix drug core. Exposure of the agent matrix to the tear fluid effects an effective therapeutic agent release into the tear fluid over a sustained period. The body has a sheath disposed over the agent matrix to inhibit release of the agent away from the proximal end. The body also has an outer surface configured to engage luminal wall tissues so as to inhibit expulsion when disposed therein. In specific embodiments, the agent matrix comprises a non-bioabsorbable polymer, for example silicone in a non-homogenous mixture with the agent.

Claims

1. A method of treating glaucoma of a patient with a punctal plug, the method comprising:

placing the punctal plug in a lacrimal canaliculus of an eye, 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 the sheath body is configured to provide an exposed proximal end of the drug core in direct contact with tear fluid that releases therapeutic agent to the eye when the drug insert is disposed within a channel of the punctal plug and the punctal plug is inserted into the lacrimal canaliculus of the patient;

wherein the distal end of the drug insert is sealed with an adhesive, and

wherein the method comprises delivering at least 10 ng per day of the therapeutic agent from the punctal plug to the eye of the patient for at least 21 days.

2. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of latanoprost, bimatoprost, timolol maleate and cyclosporin.

3. The method of claim 1, wherein the therapeutic agent is latanoprost or bimatoprost and wherein about 3 micrograms to about 135 micrograms of latanoprost or bimatoprost is present in the plug and wherein about 10 nanograms to about 150 nanograms of latanoprost or bimatoprost is released each day from the punctal plug.

4. The method of claim 1, wherein the therapeutic agent is timolol maleate, wherein about 270 micrograms to about 1350 micrograms timolol maleate is present in the plug, and wherein about 3 micrograms to about 15 micrograms timolol maleate is released each day from the punctal plug.

5. The method of claim 1, wherein the therapeutic agent is cyclosporin and wherein about 50 nanograms to about 100 nanograms cyclosporin is released each day from the plug.

6. The method of claim 1, wherein the drug core comprises a matrix that contains inclusions of the therapeutic agent.

7. The method of claim 6, wherein:

a) the inclusions comprise droplets of an oil of the therapeutic agent, and the therapeutic agent is latanoprost, or

b) the inclusions comprise solid particles of the therapeutic agent and the therapeutic agent is bimatoprost.

8. The method of claim 6, wherein the inclusions are from about 1 micrometer to about 100 micrometers in size.

9. The method of claim 1, wherein the drug core matrix comprises a non-biodegradable polymer selected from the group consisting of silicone, an acrylate, a polyethylene, polyurethane, and polyester.

10. The method of claim 9, wherein the non-biodegradable polymer comprises silicone.

11. The method of claim 1, wherein the drug core comprises a non-homogenous mixture of silicone and the therapeutic agent.

12. The method of claim 1, wherein the drug core further comprises one or more additives to increase or decrease solubility of the therapeutic agent for control of release of the therapeutic agent.

13. The method of claim 12, wherein the one or more additives is selected from the group consisting of surfactants, tinuvin, salts and water.

14. The method of claim 1, wherein said delivering comprises delivering the therapeutic agent from the punctal plug into the tear film of the subject'"'"'s eye initially at a first rate, and then at a second rate lower than the first rate.