Lacrimal implants and related methods

• US 9,445,944 B2
• Filed: 02/28/2014
• Issued: 09/20/2016
• Est. Priority Date: 09/07/2007
• Status: Active Grant

• Current Assignee: Mati Therapeutics, Inc
• Original Assignee: Mati Therapeutics, Inc
• Inventors: Rapacki, Alan R., Rubinchik, Valery, Holds, John B., Sim, Sylvie, Shen, Danny
• Primary Examiner(s): Wiest, Philip R
• Application Number:
  US14/192,915
• Publication Number:
  US 20140180253A1
• Time in Patent Office: 935 Days
• Field of Search: 604 8- 10
• US Class Current: 1/1
• CPC Class Codes: A61F 2210/0061 swellable
• 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 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/00772 Apparatus for restoration of tear ducts
• CPC Class Codes: Y10T 407/19 Rotary cutting tool
• CPC Class Codes: Y10T 409/304256 Means to remove flash or burr

Abstract

Lacrimal implants for treating diseases or disorders are disclosed. More particularly, lacrimal implants, methods of making such implants, and methods of treating ocular, respiration, inner ear or other diseases or disorders using such implants are disclosed.

Claims

1. A method of providing a sustained drug release to an eye using a lacrimal implant comprising at least one drug insert, the method comprising:

implanting the lacrimal implant in at least one lacrimal canaliculus, the lacrimal implant comprising;

an implant body, comprising a first and second portions, the implant body non-linearly extending from a proximal end portion positionable within a vertical section of the lacrimal canaliculus to a distal end portion positionable within a horizontal section of the lacrimal canaliculus and having an intermediate portion therebetween, the proximal end of the first portion defining a longitudinal proximal axis and the distal end of the second portion defining a longitudinal distal axis, the first portion including a cavity;

a drug insert disposed in the cavity, the drug insert including a matrix, a therapeutic agent dissolved or dispersed in the matrix, and an impermeable sheath body disposed over at least a portion of the matrix to define at least one insert exposed surface located at or near the proximal end of the first portion implant body;

the intermediate portion partially extending in a first direction toward the proximal end portion, partially extending in a second direction toward the distal end portion, and partially extending in a third direction along the longitudinal distal axis, configured to bias against a portion of a lacrimal canaliculus ampulla wherein the third direction is perpendicular to the first direction of the intermediate portion, such that, when implanted in the lacrimal canaliculus, the implant body directionally biases laterally against at least a portion of the lacrimal canaliculus located at or more distal to a canalicular curvature;

wherein the drug insert is configured to provide a sustained release of the therapeutic agent; and

delivering the sustained release therapeutic agent over an extended period of at least one day to the eye, whereby a sustained drug release is provided to the eye.

2. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of thrombin inhibitors;

antithrombogenic agents;

thrombolytic agents;

fibrinolytic agents;

vasospasm inhibitors;

vasodilators;

antihypertensive agents;

antimicrobial agents;

antibiotic agents;

antifungal agents;

antiviral agents;

inhibitors of surface glycoprotein receptors;

antiplatelet agents;

antimitotics;

microtubule inhibitors;

anti-secretory agents;

active inhibitors;

remodeling inhibitors;

antisense nucleotides;

anti-metabolites;

antiproliferatives;

anticancer chemotherapeutic agents;

anti-inflammatories;

non steroidal anti-inflammatories (NSAIDs);

prostaglandins, prostaglandin analogues, antiprostaglandins, prostaglandin precursors, acetazolamide, dorzolamide, brinzolamide, methazolamide, dichlorphenamide, diamox;

lubezole, nimodipine, pilocarpine, carbachol, physostigmine and combinations thereof.

3. The method of claim 1, wherein the therapeutic agent is a glaucoma drug selected from Timolol, betaxolol, levobunolol, atenolol, bimatoprost, travoprost, and latanoprost.

4. The method of claim 1, wherein the sustained drug release provided to the eye treats at least one of glaucoma, pre- and post-surgical ocular treatments, dry eye, anti-eye allergy, anti-infective, or post-surgical inflammation or pain.

5. The method of claim 1, wherein the longitudinal length of the lacrimal implant body positionable within the vertical section of the lacrimal canaliculus is less than four times a longitudinal length of the implant-body positionable within the horizontal section of the lacrimal canaliculus.

6. The method of claim 1, wherein the first direction extension of the intermediate portion of the lacrimal implant is at an angle between 45 degrees and 135 degrees relative to the second direction extension of the intermediate portion.

7. The method of claim 1, wherein the second direction extension of the lacrimal implant includes a longitudinal dilator having a generally convex shape relative to the first direction extension.

8. The method of claim 1, wherein the second direction extension of the lacrimal implant includes a longitudinal dilator having an axis substantially perpendicular to an axis of the first direction extension.

9. The method of claim 1, wherein at least one of the proximal end portion or the distal end portion of the lacrimal implant comprises at least one intermediately-disposed annular, semi-annular, column-like, or barrel-like projection, the intermediately-disposed projection having a cross-sectional size greater than an adjacent implant body portion.

10. The method of claim 1, wherein the lacrimal implant comprises a fluid swellable material disposed on an outer surface portion of the implant body, the fluid swellable material configured to expand an outer surface diameter portion of the implant body-when implanted.

11. The method of claim 1, wherein the lacrimal implant further comprises a second drug insert disposed in the distal end portion.

12. The method of claim 1, wherein the lacrimal implant comprises a first drug insert and a second drug insert, wherein the first drug insert comprises a therapeutic agent configured to treat an eye disorder;

and

the second drug insert is disposed in a second cavity in the distal end portion, wherein the second drug insert comprises a therapeutic agent configured to be received by a nasal passage.

13. The method of claim 1, wherein the second portion of the lacrimal implant includes an integral dilator, the integral dilator narrowing from a location near a proximal end of the second portion to the distal end of the second portion to facilitate implantation of the implant body into the lacrimal canaliculus.

14. The method of claim 13, wherein a diameter of an integral dilator tip is between about 0.2 millimeters and about 0.5 millimeters.

15. The method of claim 13, wherein an outer surface slope of the integral dilator, as measured from the location near the proximal end of the second portion to the distal end of the second portion, is between about 1 degree and about 10 degrees with respect to the distal axis.

16. The method of claim 1, wherein the matrix comprises silicone, acrylates, polyethylenes, polyurethane, polyurethane, hydrogel, polyester, polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether ether ketone (PEEK), nylon, extruded collagen, polymer foam, silicone rubber, polyethylene terephthalate, ultra high molecular weight polyethylene, polycarbonate urethane, polyurethane, polyimides, stainless steel, nickel-titanium alloy, titanium, stainless steel, cobalt-chrome alloy, protein, 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) or combinations thereof.

17. The method of claim 1, wherein the matrix comprises silicone or polyurethane.

18. A method of treating an ocular disorder by providing a sustained drug release to an eye using a lacrimal implant comprising at least one drug insert, the method comprising:

implanting the lacrimal implant in a lacrimal canaliculus, wherein the lacrimal implant comprises;

an implant body, comprising a first and second portions, the implant body non-linearly extending from a proximal end portion positionable within a vertical section of the lacrimal canaliculus to a distal end portion positionable within a horizontal section of the lacrimal canaliculus and having an intermediate portion therebetween, the proximal end of the first portion defining a longitudinal proximal axis and the distal end of the second portion defining a longitudinal distal axis, the first portion including a cavity;

a drug insert disposed in the cavity, the drug insert including a matrix, a therapeutic agent dissolved or dispersed in the matrix, and an impermeable sheath body disposed over at least a portion of the matrix to define at least one insert exposed surface located at or near the proximal end of the first portion implant body;

the intermediate portion partially extending in a first direction toward the proximal end portion, partially extending in a second direction toward the distal end portion, and partially extending in a third direction along the longitudinal distal axis, configured to bias against a portion of a lacrimal canaliculus ampulla wherein the third direction is perpendicular to the first direction of the intermediate portion, such that, when implanted in the lacrimal canaliculus, the implant body directionally biases laterally against at least a portion of the lacrimal canaliculus located at or more distal to a canalicular curvature;

wherein the drug insert is configured to provide a sustained release of the therapeutic agent; and

delivering the sustained release therapeutic agent over an extended period of at least one day to the eye, whereby the ocular disorder is treated.

19. The method of claim 18, wherein the therapeutic agent is selected from Timolol, betaxolol, levobunolol, atenolol, bimatoprost, travoprost, latanoprost, antimicrobial agents;

antibiotic agents;

antifungal agents;

antiviral agents;

anti-inflammatories;

or non steroidal anti-inflammatories (NSAIDs).

20. The method of claim 19, wherein the ocular disorder is at least one of glaucoma, dry eye, anti-eye allergy, ocular infection, or post-surgical inflammation or pain.

21. The method of claim 18, wherein the matrix comprises silicone, acrylates, polyethylenes, polyurethane, polyurethane, hydrogel, polyester, polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether ether ketone (PEEK), nylon, extruded collagen, polymer foam, silicone rubber, polyethylene terephthalate, ultra high molecular weight polyethylene, polycarbonate urethane, polyurethane, polyimides, stainless steel, nickel-titanium alloy, titanium, stainless steel, cobalt-chrome alloy, protein, 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) or combinations thereof.

22. The method of claim 18, wherein the matrix comprises silicone or polyurethane.

23. A method of treating ocular, respiratory, inner ear, pulmonary, or inflammatory disorder using a lacrimal implant comprising at least one drug insert, the method comprising:

implanting the lacrimal implant in a lacrimal canaliculus, wherein the lacrimal implant comprises;

an implant body, comprising a first and second portions, the implant body non-linearly extending from a proximal end portion positionable within a vertical section of a lacrimal canaliculus to a distal end portion positionable within a horizontal section of the lacrimal canaliculus and having an intermediate portion therebetween, the proximal end of the first portion defining a longitudinal proximal axis and the distal end of the second portion defining a longitudinal distal axis, the first and/or second portion including a cavity;

a drug insert disposed in the cavity, the drug insert including a matrix, a therapeutic agent dissolved or dispersed in the matrix, and an impermeable sheath body disposed over at least a portion of the matrix to define at least one insert exposed surface located at or near the proximal end of the first portion or the distal end of the second portion;

the intermediate portion partially extending in a first direction toward the proximal end portion, partially extending in a second direction toward the distal end portion, and partially extending in a third direction along the longitudinal distal axis, configured to bias against a portion of a lacrimal canaliculus ampulla wherein the third direction is perpendicular to the first direction of the intermediate portion, such that, when implanted in the lacrimal canaliculus, the implant body directionally biases laterally against at least a portion of the lacrimal canaliculus located at or more distal to a canalicular curvature;

wherein the drug insert is configured to provide a sustained release of the therapeutic agent; and

delivering the therapeutic agent over an extended period of at least one day to an eye, nasal passage or inner ear whereby at least one of the ocular, respiratory, inner ear or inflammatory disorders is treated.

24. The method of claim 23, wherein the matrix comprises silicone or polyurethane.

25. The method of claim 24, wherein the lacrimal implant comprises a first drug insert and a second drug insert, wherein the first drug insert comprises a therapeutic agent configured to treat an eye disorder;

and

the second drug insert is disposed in a second cavity in the distal end portion, wherein the second drug insert comprises a therapeutic agent configured to be received by a nasal passage.

26. The method of claim 25, wherein the therapeutic agent is selected from the group consisting of thrombin inhibitors;

antithrombogenic agents;

thrombolytic agents;

fibrinolytic agents;

vasospasm inhibitors;

vasodilators;

antihypertensive agents;

antimicrobial agents;

antibiotic agents;

antifungal agents;

antiviral agents;

inhibitors of surface glycoprotein receptors;

antiplatelet agents;

antimitotics;

microtubule inhibitors;

anti-secretory agents;

active inhibitors;

remodeling inhibitors;

antisense nucleotides;

anti-metabolites;

antiproliferatives;

anticancer chemotherapeutic agents;

anti-inflammatories;

non steroidal anti-inflammatories (NSAIDs);

prostaglandins, prostaglandin analogues, antiprostaglandins, prostaglandin precursors, acetazolamide, dorzolamide, brinzolamide, methazolamide, dichlorphenamide, diamox;

lubezole, nimodipine, pilocarpine, carbachol, physostigmine and combinations thereof.

27. The method of claim 23, wherein the matrix comprises silicone, acrylates, polyethylenes, polyurethane, polyurethane, hydrogel, polyester, polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether ether ketone (PEEK), nylon, extruded collagen, polymer foam, silicone rubber, polyethylene terephthalate, ultra high molecular weight polyethylene, polycarbonate urethane, polyurethane, polyimides, stainless steel, nickel-titanium alloy, titanium, stainless steel, cobalt-chrome alloy, protein, 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) or combinations thereof.