CN102112076B - Lacrimal implants and related methods - Google Patents

Abstract

The present invention discloses lacrimal implants for treating diseases or conditions. More specifically, the invention discloses lacrimal implants, methods of making the lacrimal implants, and methods of using the implants to treat eye, respiratory, inner ear, or other diseases or conditions.

Description

Lacrimal implants and related methods

priority statement

This application claims the benefit of U.S. Provisional Application No. 60/970,696, filed September 7, 2007, U.S. Provisional Application No. 60/970,720, filed September 7, 2007, U.S. Provisional Application No. 60, filed September 21, 2007 .60/974,367, U.S. Provisional Application No. 61/033,211, filed March 3, 2008, U.S. Provisional Application No. 61/036,816, filed March 14, 2008, U.S. Provisional Application No. 61/036,816, filed April 30, 2008 No. 61/049,360, U.S. Provisional Application No. 61/052,595, filed May 12, 2008, and U.S. Provisional Application No. 61/075,309, filed June 24, 2008, all of the specifications of said applications The contents are hereby incorporated by reference.

technical field

This patent document relates generally to ophthalmic devices, and in particular to ocular implants. More specifically, but not in a limiting manner, this patent document relates to lacrimal implants, methods of making these implants, and the use of these implants to treat eye, respiratory, inner ear, or other diseases or conditions ( For example, methods for pulmonary disorders or immune disorders).

Background technique

Dry eye, including keratoconjunctivitis sicca, is a common eye condition requiring treatment. Dry eye has been experienced by a wide range of populations and is prevalent in the elderly population. A variety of current treatments target physiological conditions that contribute to dry eye, including methods that increase normal tear flow, enhance production of tear film components, and enhance tear residence time, such as blocking tear flow from the eye into or through the lacrimal canaliculus.

Many current tear flow blocking techniques have disadvantages, including being irreversible in nature. For example, certain tear block techniques involve sealing the punctal opening by suturing the punctal opening shut or by sealing off the duct of the canaliculus using electrical or laser ablation. While these procedures can provide the desired result of blocking tear flow to treat dry eye, unfortunately, these procedures are irreversible without reconstructive surgery.

In addition to dry eye symptom relief, patients and physicians face various challenges in the area of treatment of ocular, respiratory, and inner ear diseases or conditions, including the delivery of appropriate drugs or other therapeutic agents to the eye, nasal passages, or inner ear. In ocular therapy, for example, many current ocular drug delivery systems require repeated manual administration and are often ineffective due to lack of patient compliance or inappropriate drug concentrations reaching the eye.

To treat ocular infections, inflammations of the eye, glaucoma, and other ocular diseases or conditions, drugs and other therapeutic agents often need to be applied to the eye. The traditional method of drug delivery is by applying topical drops to the surface of the eye. Topical eye drops, while effective, are less effective. As an example, when eye drops are instilled in the eye, the eye drops often overfill the conjunctival sac (i.e., the bag between the eyeball and the eyelid), causing most of the eye drop to be lost due to overflow of the eyelid margin and overflow to the cheeks. Additionally, a substantial portion of the eye drops remaining on the ocular surface can be washed into and through the canaliculus, thereby diluting the concentration of the drug before the eye drops can absorbably treat the eye. Furthermore, topically applied drugs have the highest ocular effect approximately two hours after application, after which time the drug should be reapplied to maintain the desired therapeutic effect of the drug, but this is usually not the case.

Because of the difficulty of cooperating with eye treatments, patients often do not use their eye drops as prescribed. This poor compliance may be due to, for example, the initial stinging or burning sensation caused by the eye drops and experienced by the patient. It is difficult for a person to put eye drops into their own eyes, in part because of the normal reflex of protecting the eye. Therefore, one or more droplets will avoid the eye. Elderly patients can have additional problems with dripping due to arthritis, instability and diminished vision. Pediatric populations and psychiatric populations also pose difficulties.

In areas distinct from eye therapy, respiratory-related management (e.g., anaphylaxis) and inner ear diseases or conditions often require repeated artificial digestion or inhalation of other medicinal products (e.g., drugs or other therapeutic agents), and Failure may thus occur due to lack of patient compliance or non-targeted dosing.

Contents of the invention

The present inventors have recognized a number of promising techniques to increase the residence time of tears on the eye and to deliver drugs or other therapeutic agents to the eye, nasal passages, inner ear, or other systems. These techniques may include placement of a removable, and optionally drug releasing, lacrimal implant through the punctum and into the associated canaliculus. It is believed that by designing a lacrimal implant utilizing the features of the nasolacrimal drainage system, patient comfort and retention of the implant within the ocular anatomy can be met. In this way, the lacrimal implants of the present invention can overcome certain disadvantages associated with current dry eye relief (e.g., irreversible in nature) and ophthalmic administration (e.g., artificial droplet instillation or ingestion), such as Poor patient compliance, waste, ill-timed application, or non-targeted delivery.

Additionally, the present inventors have recognized that lacrimal implants may benefit from one or more of the following capabilities: the ability to be easily implanted and removed without substantially biasing the punctum or associated canaliculus the ability to remain fixedly in the canaliculus upon implantation, optionally without being pre-sized to a specific punctum or canaliculus; to allow tear flow, medicine or other agents to flow into the nasolacrimal capacity in the system; and, when formed and used as a drug delivery system, the ability to permit local sustained release of one or more drugs or other therapeutic agents at desired therapeutic levels over extended periods of time.

A lacrimal implant for treating a disease or condition is disclosed. More specifically, lacrimal implants, methods of making these implants, and methods of using these implants to treat ocular, respiratory, inner ear, pulmonary, or immune diseases or conditions are disclosed.

To better illustrate the subject matter described herein, a non-limiting list of exemplary aspects and embodiments is provided here:

1. A lacrimal gland implant capable of being inserted into the lacrimal canaliculus, said lacrimal gland implant comprising:

an implant body comprising a first portion and a second portion, the implant body extending from a proximal end of the first portion to a distal end of the second portion;

a proximal end of the first portion defines a proximal longitudinal axis, and a distal end of the second portion defines a distal longitudinal axis;

said first portion includes a lumen extending inwardly from a proximal end of said first portion and a drug insert disposed in said lumen of said first portion to provide sustained release of a drug or other therapeutic agent to the eye,

The implant body is configured such that when implanted in the canaliculus, there is an angled intersection between the longitudinal proximal axis and the longitudinal distal axis for inserting the at least a portion of the implant body is biased against at least a portion of the canaliculus at the canaliculus bend or at a more distal end of the canaliculus bend; and

Wherein, the longitudinal length of the second portion of the implant body has a magnitude less than four times the longitudinal length of the first portion of the implant body.

2. The lacrimal implant according to aspect 1, wherein the implant body is configured such that, prior to implantation in the canaliculus, between the longitudinal proximal axis and the longitudinal distal axis There are angled intersections.

3. The lacrimal implant according to any one of aspects 1 or 2, wherein the implant body is configured to partially or completely inhibit fluid flow into and through the canaliculus.

4. The lacrimal implant according to any one of aspects 1 to 3, wherein the distal end of the first portion is at or near the proximal end of the second portion integral with the second part.

5. The lacrimal implant according to any one of aspects 1 to 4, wherein one or both of said first part and said second part comprises a fluid swellable (fluid swellable) configured to expand the holding element.

6. The lacrimal implant according to aspect 5, wherein said second portion comprises said fluid-swellable retention element configured to expands transversely relative to the longitudinal proximal axis of the first portion.

7. The lacrimal implant according to aspect 5 or 6, wherein the fluid-swellable retaining element comprises a structure configured to extend laterally in a direction away from the ampulla of the lacrimal duct when the implant body is implanted. part of the expansion.

8. The lacrimal implant according to any one of aspects 5 to 7, wherein said fluid-swellable retention element comprises a A portion that expands laterally in the direction of the abdomen.

9. The lacrimal implant according to any one of aspects 1 to 8, wherein the second portion comprises an expandable retention element comprising a coil, braid, stent, mesh , at least one of sutures, thermosetting polymers, thermoplastics, heat-activatable materials, and shape-memory materials, the expandable retention element configured to expand laterally when the implant body is implanted, to form the angled intersection.

10. The lacrimal implant according to any one of aspects 1 to 9, comprising an expandable retention element arranged around a portion of the second portion, the expandable retention element The second portion is configured to bias the second portion away from the wall of the canaliculus when inflated.

11. The lacrimal implant according to any one of aspects 1 to 10, wherein the second portion comprises an arm member movable between a first configuration and a second configuration; The first configuration can be arranged along the implant body for insertion into the canaliculus, and can extend laterally from a side of the implant body in the second configuration.

12. The lacrimal implant according to any one of aspects 1 to 11, wherein the second portion comprises an integral dilator generally extending from the proximal end of the second portion A proximal location to the distal end of the second portion narrows to facilitate implantation of the implant body into the canaliculus.

13. The lacrimal implant of aspect 12, wherein the diameter of the integral dilator tip is between about 0.2 mm and about 0.5 mm.

14. The lacrimal implant according to any one of aspects 12 or 13, wherein the expansion of the one piece to the distal end of the second portion is measured from a position near the proximal end of the second portion The angle of inclination of the outer surface of the device relative to the longitudinal distal axis is between about 1 degree and about 10 degrees.

15. The lacrimal implant according to any one of aspects 1 to 14, wherein the second portion comprises at least one undulation.

16. The lacrimal implant according to any one of aspects 1 to 15, wherein at least one of said first portion and said second portion comprises at least one intermediately disposed annular, semi-annular, cylindrical or cylindrical protrusions, the intermediately disposed protrusions having a cross-sectional dimension greater than the adjacent implant body portion.

17. The lacrimal implant according to any one of aspects 1 to 16, comprising a graspable protrusion extending at least partially from a proximal end of said first portion, said graspable protrusion The protrusion is configured to seat against or near the punctum when the implant body is implanted.

18. The lacrimal implant according to aspect 17, wherein the second portion includes an element that extends or expands laterally into the ampulla of the lacrimal duct when the implant body is implanted.

19. The lacrimal implant according to any one of aspects 17 or 18, wherein when the implant body is implanted, the graspable projections run from the proximal end of the first portion along the Extends laterally in a direction parallel to or away from the eye.

20. The lacrimal implant according to any one of aspects 1 to 19, wherein the angled intersection between the longitudinal proximal axis and the longitudinal distal axis is at least about 45 degrees.

21. The lacrimal gland implant according to aspect 1 for use in the treatment of eye diseases.

22. The lacrimal implant according to aspect 1 for use in the treatment of a respiratory related condition.

23. The lacrimal implant according to aspect 1 for use in the treatment of inner ear disorders.

24. A lacrimal implant for insertion into a canaliculus, said lacrimal implant comprising:

an implant body extending non-linearly from a proximal portion positionable within the vertical section of the canaliculus to a distal portion positionable within the horizontal section of the canaliculus, and having an intermediate portion between them;

a lumen disposed in said proximal portion and a drug insertion portion disposed in said lumen of said proximal portion to provide sustained release of a drug or other therapeutic agent to the eye,

The intermediate portion extends partially in a first direction towards the proximal portion and partially in a second direction towards the distal portion such that when implanted in the canaliculus, the said implant body directionally and laterally biases at least a portion of said canaliculus at or at a more distal end of said canaliculus bend; and

Wherein, the implant body inhibits fluid flow into and through the lacrimal canaliculus.

25. The lacrimal implant according to aspect 24, wherein the implant body positionable in the vertical section of the canaliculus has a longitudinal length less than the length of the implant body positionable in the horizontal section of the canaliculus Four times the longitudinal length of the implant body.

26. The lacrimal implant according to any one of aspects 24 or 25, wherein the first directional extension of the intermediate portion is within about 45 degrees to the second directional extension of the intermediate portion. Angle between about 135 degrees.

27. The lacrimal implant according to any one of aspects 24 to 26, wherein when the implant body is implanted, the intermediate portion is along a first direction substantially opposite to the second direction. Three directions extend partially toward the ampulla of the canaliculus.

28. The lacrimal implant according to any one of aspects 24 to 27, wherein said second direction extension comprises a longitudinal dilator relative to said first direction extension having a generally concave shape; and wherein a radius of the generally concave shape is smaller than a radius of the canaliculus bend.

29. The lacrimal implant according to any one of aspects 24 to 28, wherein said second direction extension comprises a longitudinal dilator relative to said first direction extension Has a generally convex shape.

30. The lacrimal implant according to any one of aspects 24 to 29, wherein said second direction extension comprises a longitudinal dilator having a The axis of the axis is substantially perpendicular to the axis.

31. The lacrimal implant according to any one of aspects 24 to 30, wherein at least one of said proximal portion or said distal portion comprises at least one intermediately disposed annular, semi-annular, Cylindrical, or cylindrical, protrusions, the intermediately disposed protrusions having a greater cross-sectional dimension than the adjacent implant body portion.

32. The lacrimal implant according to any one of aspects 24 to 31 , comprising a graspable protrusion extending transversely from the proximal portion.

33. The lacrimal implant according to any one of aspects 24 to 32, comprising a fluid swellable material disposed on an outer surface portion of the implant body, the fluid The swellable material is configured to expand a portion of the outer surface diameter of the implant body when implanted.

34. The lacrimal implant according to any one of aspects 24 to 33, comprising a second drug insertion portion arranged in the distal portion, the One or both of the first drug insertion portion and the second drug insertion portion inhibit fluid flow through the implant body and include at least one exposed surface configured to deliver sustained release.

35. The lacrimal implant according to any one of aspects 33 or 34, comprising a lumen in the distal portion configured to receive a drug core The second medicament insertion portion of the form, the medicament core comprising a second medicament configured to be received by the nasal passage.

36. A method of making a lacrimal implant insertable into a canaliculus, the method comprising:

Forming the implant body, the implant body extends from the proximal end of the first body portion to the distal end of the second body portion, comprising:

extending the second body portion for a longitudinal length less than four times the longitudinal length of the first body portion; and

The proximal end and the distal end are configured to define, respectively, a proximal longitudinal axis and a distal longitudinal axis when implanted in the canaliculus, the proximal longitudinal axis and the distal longitudinal axis intersect at an angle such that The implant body is configured to directionally laterally bias at least a portion of the canaliculus at or at a more distal end of the canaliculus bend; and

arranging at least one of the first drug insertion portion in the first body portion and the second drug insertion portion in the second body portion includes positioning the first drug insertion portion adjacent the proximal end and at least one of the exposed surface of the second medicament insertion portion adjacent to the distal end to provide sustained release of the first medicament or the second medicament, respectively.

37. The method of aspect 36, wherein forming one or both of the first body portion and the second body portion comprises forming at least one intermediately disposed annular, semi-annular, cylindrical, or A cylindrical protrusion, the centrally disposed protrusion having a cross-sectional dimension greater than an adjacent implant body portion.

38. The method of any one of aspects 36 or 37, wherein forming the second body portion comprises forming a dilator generally from a position near the proximal end of the second body portion The distal end to the second body portion narrows.

39. The method of any one of aspects 36 to 48, wherein forming the dilator comprises forming an outer surface oblique angle of the implant body relative to the longitudinal distal axis, the implant The inclination angle of the outer surface of the object body is between about 1 degree and about 10 degrees as measured from a location near the proximal end of the second body portion to the distal end of the second body portion.

40. A method according to any one of aspects 36 to 39, wherein forming the second portion comprises arranging a fluid swellable retaining element near the distal end of the first body portion, comprising displacing the fluid The swellable retention element is arranged such that a transverse expansion of the fluid swellable retention element relative to the longitudinal proximal axis is configured to bias the lacrimal canaliculus or tear when the implant body is implanted. At least a portion of the anatomy of the tubule ampulla.

41. A method according to any one of aspects 36 to 40, comprising coating an outer surface portion of the implant body with a fluid swellable material.

These and other embodiments, advantages and aspects of the lacrimal implants and methods of the present invention are set forth in part in the detailed description that follows. This summary is intended to provide an overview of the subject matter of the patent application. It is not intended to provide an exclusive or exhaustive description of the invention. The Detailed Description is included here to provide further information on this patent application.

Description of drawings

In the drawings, the same reference numerals may be used to describe similar parts throughout the several views. The same reference number with a different letter suffix may be used to denote different instances of a similar component. The drawings generally illustrate various embodiments discussed in this document by way of example and not limitation, in which:

Figures 1 to 2 show examples of schematic diagrams of anatomical structures associated with the eye that provide a suitable environment in which lacrimal implants can be used;

Figure 3 A shows an example of an isometric view of a lacrimal implant configured to be held in the punctum and associated canaliculus anatomy, the lacrimal implant being comprised between implant body first and second portions Intersections at substantially perpendicular angles;

3B shows an example of a cross-sectional view of a lacrimal implant and an expansion of an anatomical structure receiving the implant along a line parallel to the longitudinal axis of the implant, for example along line 3B-3B;

Figure 4 shows an example of a side view of a lacrimal implant configured to be held in a punctum and associated canaliculus anatomy, the lacrimal implant including an integral dilator;

Figure 5 shows an example of a schematic diagram of a lacrimal implant held in a punctum and associated canaliculus anatomy, the lacrimal implant comprising at least one drug insertion portion;

6A shows an example of an isometric view of a lacrimal implant configured to be retained in a punctum and associated canalicular anatomy, the lacrimal implant including a portion that can be arranged within the ampulla of the canaliculus;

Figure 6B shows an example of a cross-sectional view of a lacrimal implant taken along a line parallel to the longitudinal axis of the implant, for example along line 6B-6B;

7A shows an example of an isometric view of a lacrimal implant configured to be held in a punctum and associated canaliculus anatomy, the lacrimal implant comprising a ring-shaped graspable protrusion;

Figure 7B shows an example of a cross-sectional view of a lacrimal implant taken along a line parallel to the longitudinal axis of the implant, for example along line 7B-7B;

8A shows an example of an isometric view of a lacrimal implant configured to be retained in the punctum and associated canaliculus anatomy, the lacrimal implant including a portion that can be arranged within the ampulla of the canaliculus and including a depression to facilitate insertion;

Figure 8B shows an example of a cross-sectional view of a lacrimal implant taken along a line parallel to the longitudinal axis of the implant, for example along line 8B-8B;

Figure 9 shows an example of a side view of a lacrimal implant configured to be retained in the punctum and associated canaliculus anatomy, the lacrimal implant including a recess to facilitate insertion;

Figure 10A shows an example of an isometric view of a lacrimal implant configured to be retained in a punctum and associated canalicular anatomy, the lacrimal implant including a portion that can be arranged within the ampulla of the canalicular;

Figure 10B shows an example of a cross-sectional view of a lacrimal implant taken along a line parallel to the longitudinal axis of the implant, for example along line 10B-10B;

Figures 11 to 13 show examples of side views of various lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each lacrimal implant comprising at least one centrally disposed retention protrusion ;

Figures 14 to 17 show examples of isometric views of various lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each lacrimal implant comprising at least one intermediately disposed retaining protrusion;

Figures 18 to 19 show examples of side views of lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each lacrimal implant comprising a first and a second implant Intersections at non-perpendicular angles between body parts;

20 shows an example of an isometric view of a lacrimal implant configured to be held in a punctum and associated canaliculus anatomy, the lacrimal implant comprising one or more cutouts of material;

Figures 21A to 22B show examples of side views of lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each lacrimal implant comprising one or more transversely extendable arms ;

23A to 23B show an example of a side view of a lacrimal implant configured to be retained in the punctum and associated canaliculus anatomy, the lacrimal implant comprising an inflatable implant disposed around a portion of the implant body. the holding element;

Figure 24 shows an example of an isometric view of a lacrimal implant held in a punctum and associated canaliculus anatomy;

25A to 25B show examples of isometric views of lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each including an implant having a generally concave shape. body part of the object;

26 shows an example of an isometric view of a lacrimal implant configured to be held in a punctum and associated canaliculus anatomy, the lacrimal implant comprising an implant body portion having a generally convex shape;

27 shows an example of a side view of a lacrimal implant configured to be held in a punctum and associated canaliculus anatomy, the lacrimal implant comprising an implant body portion having an undulating shape;

28 shows an example of a side view of a lacrimal implant configured to be retained in a punctum and associated canaliculus anatomy, the lacrimal implant comprising at least one centrally disposed retention protrusion;

Figures 29 to 32 show examples of side views of various lacrimal implants configured to be retained in the punctum and associated canaliculus anatomy, each including a fluid swellable retaining element ;

33 shows an example of a side view of a lacrimal implant configured to be retained in a punctum and associated canaliculus anatomy, the lacrimal implant comprising an expandable retaining element;

Figures 34A to 34B show examples of schematic diagrams of lacrimal implants configured to be held in the punctum and associated canaliculus anatomy, each lacrimal implant including directional graspable protrusions;

Figures 35 to 38 illustrate examples of isometric views of various lacrimal implant proximal portions, each proximal portion comprising a graspable protrusion or void;

Figures 39A to 39B show examples of isometric views of drug inserts and filaments to aid in removal;

FIG. 40 illustrates an example of a method of making a lacrimal implant configured to remain within a punctum and associated canaliculus anatomy.

Detailed ways

In this patent document, a lacrimal implant and related methods are described which provide secure, wedgable retention in the punctum and associated canaliculus of the eye ( wedgable retention). The lacrimal implant may include an implant body configured for at least partial insertion through the punctum and into an associated canaliculus. The implant body may include a first portion and a second portion, and the implant body may extend from a proximal end of the first portion defining a longitudinal proximal axis to a distal end of the second portion defining a longitudinal distal axis. The implant body may be configured such that there is an angled intersection between the proximal and distal axes, for example at least 45 degrees, when implanted using the integral dilator. Like this, at least a portion of the implant body can be biased to at least a portion of the canaliculus at or at a more distal end of the canalicular curvature, thereby using the anatomical structure to maintain lacrimal implantation implantation location. In various examples, the lacrimal implant may further include a drug insert including a drug insert disposed in at least one of the first portion or the second portion of the implant body, Thereby providing sustained release of drugs or other therapeutic agents to the eye, nasal passages or inner ear system.

1 to 2 show examples of schematic diagrams of the anatomy associated with an eye 100 . The anatomy shown is suitable for treatment using the various lacrimal implants and methods described herein. As shown, the eye 100 is a spherical structure comprising a wall with three layers: the outer sclera 102 , the middle choroid layer 104 and the inner retina 106 . The sclera 102 includes a tough, fibrous covering that protects the inner layers. The eye 100 is mostly white except for a clear area at the front, commonly referred to as the cornea 108 , which allows light to enter the eye 100 .

The choroidal layer 104 located within the sclera 102 contains many blood vessels and at the front of the eye 100 changes into the pigmented iris 110 . The lenticular lens 112 is located just behind the pupil. A chamber 114 located behind the lens 112 is filled with vitreous humor, which is a gel-like substance. Anterior and posterior chambers 116 are located between the cornea 108 and the iris 110, respectively, and are filled with aqueous humor. At the back of the eye 100 is the retina 106 which detects light.

The cornea 108 is an optically transparent tissue that transmits images to the back of the eye 100 . The cornea 108 comprises avascular tissue to which nutrients and oxygen are supplied from blood vessels lining the junction between the cornea 108 and the sclera 102 via bathing with tear streams and aqueous fluids. The cornea 108 includes a pathway for the drug to penetrate into the eye 100 .

Referring to Figure 2, there is shown additional anatomy associated with eye 100 including a tear drainage system including a secretion system 230, a distribution system, and a drainage system. Secretory system 230 includes secretory glands that are stimulated by blinking and temperature changes due to tear evaporation and reflex secretors that have an efferent parasympathetic innervation. nerve supply) and secrete tears in response to physical or emotional stimuli. The distribution system includes the eyelid 202 and the tear meniscus surrounding the eyelid margin of the open eye, which distributes the tear fluid across the entire ocular surface by blinking, thereby reducing the dry area to prevent the dry area from expanding.

In the order of flow drainage, the draining part of the lacrimal drainage system includes: the punctum, the canaliculus, the lacrimal sac 204 and the lacrimal duct 206 . Lacrimal fluid and other flowable substances drain from the lacrimal duct 206 into the passages of the nasolacrimal system. The canaliculus includes an upper (upper) canaliculus 208 and a lower (inferior) canaliculus 210 terminating in an upper (upper) canaliculus 212 and a lower (lower) canaliculus, respectively. Point 214. The upper and lower puncta 212, 214 are raised slightly at the medial end of the lid margin at the junction 216 of the lacrimal and ciliary portions near the conjunctival sac 218. The upper and lower puncta 212, 214 are generally circular or slightly oval openings surrounded by a connecting ring of tissue. Each punctum 212 , 214 opens into the vertical portion 220 , 222 of their respective canaliculus before becoming more horizontal at the canaliculus bend 250 to interconnect at the entrance of the lacrimal sac 204 . The canaliculi 208, 210 are generally tubular and lined with stratified squamous epithelium surrounded by elastic tissue that allows the canaliculi to dilate. As shown, a canaliculus ampulla 252 is present near the outer edge of each canaliculus bend 250 .

FIG. 3A shows an example of a lacrimal implant 300 that can be inserted through the punctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2). Insertion of the lacrimal implant 300 through the punctum 212, 214 and into the associated canaliculus 208, 210 may allow for one or more of the following: inhibiting or blocking the passage of tears (eg, to treat dry eye ), or sustained delivery of drugs or other therapeutic agents to the eye (e.g., to treat infection, inflammation, glaucoma, or other ocular diseases or conditions), the nasal passages (e.g., to treat sinus or allergic conditions), or the inner ear system (for example, to treat dizziness or migraine).

As shown in this example, a lacrimal implant 300 can include an implant body 302 that includes a first portion 304 and a second portion 306 and can extend from a proximal end 308 of the first portion 304 to The distal end 310 of the second portion 306 . In various examples, proximal end 308 can define a longitudinal proximal axis 312 and distal end 310 can define a longitudinal distal axis 314 . The implant body 300 can be configured such that there is an angled intersection 316 of at least 45 degrees between the proximal axis 312 and the distal axis 314 when implanted in the punctum and associated canaliculus for use in At least a portion of the implant body 302 is biased against at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) located at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ). In some examples, the implant body 302 can be configured such that the angled intersection 316 is between about 45 degrees and about 135 degrees. In this example, the implant body 302 is configured such that the angled intersection 316 is approximately 90 degrees (ie, the intersection 316 is approximately vertical). In various examples, the distal end 326 of the first portion 304 may be integral with the second portion 306 at or near the proximal end 328 of the second portion 306 .

In some examples, the implant body 302 can include an angularly disposed cylindrical structure including a first lumen 318 disposed near the proximal end 308 or a first lumen 318 disposed near the distal end 310. One or both of the two cavities 320 . In this example, a first lumen 318 extends inwardly from the proximal end 308 of the first portion 304 and a second lumen 320 extends inwardly from the distal end 310 of the second portion 306 . A first drug-releasing or other drug-releasing insert (e.g., a drug core) 322 may be disposed in the first cavity 318 to provide sustained release of the drug or other therapeutic agent, for example, to the eye, while in the second cavity 320 A second drug-releasing or other drug-releasing insert (eg, drug core) 324 may be disposed therein to provide sustained release of drugs or other therapeutic agents to the nasal passages or inner ear system. An implant body septum 330 can be positioned between the first lumen 318 and the second lumen 320, and the implant body septum 330 can be used to inhibit or prevent material (e.g., medicament) from entering the first medicament insertion portion 322. It communicates with the second drug insertion part 324 . In some examples, the implant body 302 is solid and does not include one or more lumens or other voids.

In some examples, release of the drug or other therapeutic agent may occur at least in part via exposed, non-sheath covered surfaces of the drug insertion portion 322 , 324 . In some examples, by controlling the geometry of the exposed surface, a predetermined rate of drug or agent release can be achieved. For example, the exposed surface may be configured with specific geometries or other techniques suitable for controlling the rate of release of drugs or other therapeutic agents to the eye 100, such as on an acute or chronic basis, between physician visits in an outpatient setting. Information on one or more drugs or other therapeutic agents from the drug inserts 322, 324 can be found in commonly owned U.S. Patent Application No. 11/695,545, entitled "NASOLACRIMAL DRAINAGE SYSTEM IMPLANTS FOR DRUG THERAPY" by DeJuan et al Further description of the effective release rate.

In some examples, such as shown in FIG. 3B , the exposed surfaces of the drug insertion portions 322 , 324 may be flush with the proximal end 308 of the first portion 304 or the distal end 310 of the second portion 306 , respectively, or may be flush with the distal end 310 of the second portion 306 , respectively. Slightly below the proximal end 308 of the first portion 304 or the distal end 310 of the second portion 306 so that the drug insertion portion does not protrude outside of the implant body 302 . In some examples, such as shown in FIG. 4 , for example, the exposed surface of the first drug insertion portion 322 can be positioned above the proximal end 308 such that the first drug insertion portion 322 protrudes at least partially into the implant body 302 of the exterior.

The implant body 302 may include a graspable or other protrusion 332 , such as one or more protrusions extending at least partially laterally from or around the proximal end 308 of the implant body first portion 304 . In some examples, the graspable or other protrusion 332 may include a set of wings for inserting the lacrimal implant 300 into or removing the lacrimal implant from the implant site. Object 300. The set of wings or other projections 332 can be configured without migration in mind, since the non-linear configuration of the implant body 302 can be achieved by taking the canaliculus bend 250 and optionally the tear duct. The size or shape of the small tubule ampulla 252 ( FIG. 2 ) prevents implant 300 from migrating. In some examples, the graspable or other protrusion 332 may be configured to seat against or near the punctal opening 212, 214, for example to inhibit or prevent complete passage of the lacrimal implant 300 within the canaliculus 208, Or to provide eg tactile or visual feedback to the implant user as to whether the implant is fully implanted.

As shown in FIGS. 34A-34B , and discussed below, the graspable or other protrusions 332 may extend laterally in a direction parallel to the eye 100 or away from the eye 100 when implanted. This can reduce irritation to the eye 100 compared to the case where the protruding portion extends toward the eye 100 . Additionally, the direction in which the protrusion 332 extends laterally from the proximal end 308 may be substantially the same as the direction in which the second implant body portion 306 extends laterally relative to the distal end 326 of the first implant body portion 304, as shown, for example, in FIGS. 3A-3B . . This also avoids extension towards the eye. The first drug insertion portion 322 may extend partially through the area of the protrusion 332, for example, to provide sustained release of the first drug or other therapeutic agent to the eye.

In various embodiments, the implant body 302 can be molded using a resilient material, such as silicone, polyurethane or other urethane-based polymers or copolymers, NuSil (eg, NuSil4840 with 2% 6-4800 ) or non-biodegradable, partially biodegradable, or biodegradable (i.e., erodible in the body) acrylic, thereby allowing the implant body 302 to be configured so that when implanted in the canaliculus 208, 210 , there is an angled intersection 316 between the proximal axis 312 and the distal axis 314 to be formed. In some examples, the biodegradable elastic material can include a cross-linked polymer, such as poly(vinyl alcohol). In some examples, implant body 302 may comprise a silicone/polyurethane copolymer. Other copolymers that can be used to form the implant body 302 include, but are not limited to, silicone/urethane, silicone/poly(ethylene glycol) (PEG), and silicone/2-hydroxyethyl methacrylate (2hydroxyethyl methacrylate) (HEMA). As discussed in commonly owned U.S. Patent Application No.____, Attorney Docket No. 2755.045US1, entitled "DRUG CORESFOR SUSTAINED RELEASE OF THERAPEUTIC AGENTS," filed on the same date by Utkhede et al., urethane-based polymers Polymer or copolymer materials allow multiple processing methods and combine well with each other.

Figure 3B shows an example of a cross-sectional view of the lacrimal implant 300 taken along a line parallel to the longitudinal axis of the implant, for example along line 3B-3B of Figure 3A. As shown in FIG. 3B , a lacrimal implant 300 can include an implant body 302 that includes a first portion 304 and a second portion 306 and can extend from a proximal end 308 of the first portion 304 to a second portion. The distal end 310 of the second part 306. In various examples, proximal end 308 can define a longitudinal proximal axis 312 and distal end 310 can define a longitudinal distal axis 314 . The implant body 300 can be configured such that when implanted, there is an angled intersection 316 of at least 45 degrees between the proximal axis 312 and the distal axis 314, so that at least a portion of the implant body 302 A bias is applied to at least a portion of the canaliculus 208 , 210 at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ). In this example, the implant body 300 is configured such that the angled intersection 316 is approximately 90 degrees.

In various examples, the distal end 326 of the first portion 304 can be integral with the second portion 306 at or near the proximal end 328 of the second portion 306 . In some examples, the length of the second portion 306 may be an amount less than four times the length of the first portion 304 . In one embodiment, the second portion 306 may be less than about 10 millimeters in length and have a configuration similar to that shown in FIG. 3B . In another example, the second portion 306 may be less than about 2 millimeters in length and have a configuration similar to that shown in FIG. 24 .

In various examples, the second portion 306 can include an integral dilator 350 to dilate an anatomical tissue 352, such as one or both of the punctum 212, 214 or associated canaliculus 208, 210 (FIG. They are dilated to a sufficient diameter when the lacrimal implants 300 are implanted. In this way, the lacrimal implant 300 can be implanted into ocular anatomy of various sizes without the need for pre-dilation via a separate enlargement tool. The dilator 350 may be formed so as not to damage the lining of the puncta 212 , 214 and the canaliculi 208 , 210 . In some examples, a lubricious coating disposed on or impregnated into the outer surface of the implant body 302 may be used to further facilitate insertion of the lacrimal implant 300 into the anatomical tissue 352 middle. In one example, the lubricious coating may include a silicon lubricant.

As shown, the dilator 350 can generally narrow from a position near the proximal end 328 of the second portion 306 to the distal end 310 of the second portion 306, for example, from a diameter of about 0.6 mm to a diameter of about 0.2 mm . In some examples, the angle of inclination of the outer surface of the dilator 350 relative to the longitudinal distal axis 314 as measured from a position near the proximal end 328 of the second portion 306 to the distal end 310 of the second portion 306 can be between about 1 degrees and about 10 degrees (eg, 2 degrees, 3 degrees, 4 degrees, or 5 degrees). In some examples, the angle of inclination of dilator 350 relative to longitudinal distal axis 314 may be less than 45 degrees. The desired slope of the dilator 350 for a given implant location can be determined by, among other factors, balancing the strength of the implant body 302 desired for implantation with the desire to have a soft, flexible texture when implanted. A conforming implant body (eg, conforming to the canaliculus anatomy) is determined. In some examples, dilator tip 354 may have a diameter between about 0.2 millimeters and about 0.5 millimeters.

In some examples, the proximal end 328 of the implant body second portion 306 can include a retaining element 356 configured to bias at least a portion of the ampulla of the lacrimal canaliculus 252 ( FIG. 2 ) upon implantation. In this example, the retaining element 356 protrudes proximally from the intersection between the implant body first portion 304 and the implant body second portion 306 , for example in a direction opposite to the extension of the dilator 350 . When the retention element 356 is present and implanted in the ampulla 252 , the retention element 356 can help secure the seated position of the graspable or otherwise protrusion 332 against the punctal opening 212 , 214 .

In some examples, the implant body 302 includes a first lumen 318 disposed near the proximal end 308 . In this example, the first lumen 318 extends inwardly from the proximal end 308 by about 2 millimeters or less and accommodates a first drug-releasing or other drug-releasing insert 322 to provide drug or other therapeutic agent to the eye. Sustained release. In some examples, drug insertion portion 322 may include inclusions 360 of various therapeutic agents, which may be distributed in matrix 362 . In some examples, inclusions 360 may include a concentrated form (eg, a crystalline form) of a therapeutic agent. In some examples, matrix 362 may comprise a silicone matrix or the like, and the distribution of inclusions 360 within the matrix may be substantially homogeneous or heterogeneous. In some examples, agent inclusions 360 may include oil droplets such as Latanoprost oil. In other examples, agent inclusions 360 may include solid particles such as Bimatoprost particles in crystalline form. In certain examples, the drug insert 322 comprises a urethane-based (eg, polyurethane) polymer or copolymer that includes inclusions of therapeutic agents that can be delivered into the eye or surrounding tissue. Inclusions can be of various sizes and shapes. For example, inclusions may include particles having a size from about 1 micron to about 100 microns. Drugs that release drugs or that release other agents can be found in commonly owned U.S. Patent Application No. ___, Attorney Docket No. 2755.045US1, entitled "DRUG CORES FORSUSTAINED RELEASE OF THERAPEUTIC AGENTS," filed on the same date by Utkhede et al. Further discussion in the Insert section.

In various examples, the drug insertion portion 322 can include a sheath 366 disposed over at least a portion of the insertion portion to define at least one insertion portion exposed surface 368 . The exposed surface 368 may, for example, be positioned at or near the proximal end 308 of the implant body 302, whereby when the lacrimal implant 300 is inserted through the punctum 212, 214 and into the associated canaliculus 208, 210, The exposed surface 368 is allowed to come into direct contact with the tear or tear film fluid and release the drug or other therapeutic agent from the drug insert 322 for a sustained period of time.

FIG. 4 shows an example of a side view of another integral dilator 450 of the second portion 406 of the implant body 402 of the lacrimal implant 400 . In this example, the dilator 450 narrows abruptly near the distal end 410 of the second portion 406 . As shown, the implant body first portion 404 can include a first lumen 418 disposed near the proximal end 408 . In this example, a first lumen 418 extends inwardly from the proximal end 408 and houses a first drug-releasing or other drug-releasing drug insert 422 to provide sustained release of drug or other therapeutic agent to the eye, for example. In some examples, a drug or other therapeutic agent may be released to the eye via the exposed, non-sheath-covered surface of drug insertion portion 422 . In this example, the exposed surface 468 of the drug insertion portion 422 is positioned above the proximal end 408 such that the drug insertion portion 422 protrudes at least partially outside of the implant body 402 .

In various examples, the outer surface 482 of the implant body 402 can be formed or otherwise treated to be substantially smooth to inhibit bacteria from adhering to the lacrimal implant 400 and lurking in the body. The generally smooth outer surface 482 also prevents damage to the lining of the receiving anatomy, such as the punctum 212, 214 (FIG. 2) or associated canaliculus 208, 210 (FIG. 2), during implantation. As further discussed in commonly owned U.S. Patent Application No.____, Attorney Docket No. 2755.036US1, entitled "SURFACE TREATMENT FOR IMPLANTS AND RELATED METHODS," filed on the same date by Rapacki et al., the outer surface 482 of the implant body 402 It may be a surface processed to be substantially smooth by polishing. The polishing process may include causing the molded implant body 402 to collide with a polishing medium during the ongoing period of time while the implant body 402 is in the expanded expanded state. This may smooth one or more surfaces or edges of the implant body 402 . In various examples, the polishing media can include at least some grains having a diameter greater than about 3 millimeters.

In various examples, an antimicrobial cover 484 is disposed on or penetrates at least a portion of the outer surface 482 to further prevent bacterial growth on the implant body 402 . In some examples, the antimicrobial coating 484 can include a substance selected from the group consisting of: 2-bromo-2-nitropropane-1,3-propanediol, 5-bromo-5-nitropropane 1,3-dioxane, 7-ethylbicyclooxazolidine (7-ethylbicyclooxazolidine), benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, cetyl chloride Alkyl pyridine, chlorhexidine gluconate (chlorhexidinedigluconate), chloroacetamide, chlorobutanol, chloromethylisothiazolinone (chloromethylisothiazolinone) and methylisothiazolinone (methylisothiazolinone), acetyldimethyldioxane, Dimethyl oxazolidine, dimethyldydroxymethyl pyrazole, chloroxylenol, dehydroacetic acid, diazolidinyl urea, dichlorobenzyl alcohol, DMDM hydantoin, ethanol, formaldehyde, glutaraldehyde, hexa Chlorophenes, hexetidine, hexamethylenetramine, imidazolidinyl urea, iodopropynyl butylcarbamate, isothiazolinones, methenammonium chloride, methyldibromo glutaronitrile, MDM hydantoin, minocycline, o-phenylphenol, p-chloro-m-cresol, p-hydroxy Parabens (butylparaben, ethylparaben, methylparaben), phenylethyl alcohol, phenoxyethanol, piroctone olamine, polyaminopropyl biguanide, polymethyleneoxybicycloxine Polymethoxy bicyclic oxazolidine, polyoxymethylene, polyquaternium-42, potassium benzoate, potassium sorbate, propionic acid, quaternium-15, rifampicin, salicylic acid, selenium disulfide, borax , sodium iodate, sodium hydroxymethylglycinate, sodium propionate, sodium pyrithione, sorbic acid, thimerosal, triclosan, triclocarban, undecylenic acid, zinc phenosulfonate and zinc pyrithione . In some examples, the antimicrobial coating 484 may include a material selected from the group consisting of: silver lactate, silver phosphate, silver citrate, silver acetate, silver benzoate, silver chloride, silver iodide, Silver lodate, silver nitrate, silver sulfadiazine, silver palmitate, or a mixture of one or more thereof. In some examples, antimicrobial cover 484 may include at least one of an antibiotic or an antiseptic. For example, the antimicrobial covering 484 may include a temporary anesthetic lasting between a few hours and a day on average. In other examples, the antimicrobial coating 484 may include medicines or other therapeutic agents to treat the underlying condition, such as a bolus, for immediate effect.

FIG. 5 shows an example of a schematic diagram of a lacrimal implant, such as lacrimal implant 300 shown in FIG. 3 , implanted in a lower punctum 214 and associated canaliculus 210 . In some examples, lacrimal implant 300 may be implanted in superior punctum 212 and canaliculus 208 . As noted above, the lacrimal implant 300 can include an implant body 302 that includes a first portion 304 and a second portion 306 . In various examples, the implant body 302 can be configured such that when implanted, at least a portion of the implant body 302 is biased to be located at or at the more distal end of the canalicular bend 250 At least a part of the lacrimal canaliculus 210 to securely maintain the implantation position of the implant 300 . As shown, the first portion 304 can be configured to be inserted through the punctum 214 and into the associated canaliculus 210 and rest between the punctal opening and the ampulla of the canaliculus 252, while the second portion 306 can be configured to be inserted Passes through the punctum 214 and into the canaliculus 210 and rests between the ampulla 252 and the lacrimal sac 204 . In some examples, the retaining element 356 protruding from the proximal end of the second portion 306 can be configured to be biased into and onto at least a portion of the ampulla 252 when implanted. . In various examples, the first portion 304 and the second portion 306 can be configured to bend, elongate, or collapse as desired to maintain a proper anatomical implant fit without unduly elongating the ocular anatomy. .

In some examples, in order to further fix the implant 300 in the punctum 214 and the lacrimal canaliculus 210 or to make the size of the implant body 302 adjustable, a ( For example, a swellable material coated) with a hydrogel or other fluid. The fluid swellable material is effective to expand a portion of the diameter of the outer surface of the implant body 302 when implanted. In some examples, the outer surface of the implant body 302 may include a covering of wicking material or longitudinal channels or grooves to allow fluid to flow around the implant body 302. Using one or a combination of these techniques, the lacrimal implant 300 may be configured to completely occlude the canaliculus 208, 210 or only partially occlude the canaliculus 208, 210 when implanted therein. For example, the use of longitudinal channels or grooves in either or both of the first portion 304 or the second portion 306 of the implant body 302 may allow for reduced volume, or tear drainage may occur, potentially aiding medication or other Release of therapeutic agents from the drug insertion portion.

Forceps or other insertion tool may be used to insert the lacrimal implant 300 through the puncta 212 , 214 and into the associated canaliculus 208 , 210 . In some examples, an insertion tool as described in commonly owned U.S. Patent Application No.____, Attorney Docket No. 2755.018US1, entitled "INSERTION AND EXTRACTION TOOLS FOR LACRIMAL IMPLANTS," filed on the same date by De Juan et al. To implant the lacrimal implant 300. In various examples, the second portion 306 of the implant body 302 can be advanced into the depths of the canaliculus 208, 210 by manipulating the insertion tool until a graspable or other protrusion 332 (if present) can abut against the tear Point openings 212, 214 are seated. When it is desired to remove the lacrimal implant 300, the protrusion 332 can be grasped, for example, with forceps, and the protrusion 332 can be withdrawn from the punctal opening 212,214.

In some examples, the implant body 302 can include one or both of a first lumen 318 disposed near the proximal end 308 and a second lumen 320 disposed near the distal end 310 . In this example, a first lumen 318 extends inwardly from the proximal end 308 of the first portion 304 and a second lumen 320 extends inwardly from the distal end 310 of the second portion 306 . A first drug-releasing or other drug-releasing drug insert 322 may be disposed in the first cavity 318 to provide sustained release of drug or other therapeutic agent to, for example, the eye (e.g., to treat infection, inflammation, glaucoma, or other eye disease or condition), while a second drug-releasing or other drug-releasing drug insert 324 may be disposed in the second chamber 320 for introduction to the nasal passages (for example, to treat sinus or allergic conditions) or The inner ear system (eg, to treat dizziness or migraines) provides sustained release of drugs or other therapeutic agents.

6A and 6B illustrate another example of a lacrimal implant 600 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 600 can include an implant body 602 that includes a first portion 604 and a second portion 606 and can extend from a proximal end 608 of the first portion 604 to the second portion The distal end 610 of 606 . Proximal end 608 may define a longitudinal proximal axis 612 and distal end 610 may define a longitudinal distal axis 614 . The implant body 600 can be configured such that when implanted, there is an angled intersection of approximately 90 degrees between the proximal axis 612 and the distal axis 614 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ).

In this example, the proximal end 628 of the implant body second portion 606 can include a retaining element 656 configured to bias against at least a portion of the canalicular ampulla 252 ( FIG. 2 ) when implanted. . In this example, the implant body 602 includes a first lumen 618 configured to receive a first drug-releasing or other drug-releasing drug insert, the first cavity 618 being disposed at the implant near the proximal end 608 of the first portion 604 of the object body. Also in this example, the implant body 602 can include a graspable or other protrusion 632 , such as a set of wings having a combined length of approximately 1 millimeter and extending laterally from the proximal end 308 .

Figure 6B shows an example of a cross-sectional view of the lacrimal implant 600 taken along a line parallel to the longitudinal axis of the implant, for example along line 6B-6B of Figure 6A. As shown in FIG. 6B , the distal end 626 of the first portion 604 may be integral with the second portion 606 at or near the proximal end 628 of the second portion 606 . In various examples, the second portion 606 can include a longitudinal length measured from the proximal axis 612 to the distal end 610, the longitudinal length of the second portion 606 having a magnitude less than four times the longitudinal length of the first portion 604, The longitudinal length of the first portion 604 is measured from the proximal end 608 to the distal axis 614 . In some examples, the first portion can include a longitudinal length of about 1.54 millimeters, and the second portion can include a longitudinal length of between about 4.5 millimeters and about 5.42 millimeters.

In various examples, the second portion 606 can include an integral dilator 650 to dilate anatomical tissue, such as one or both of the punctum 212, 214 (FIG. 2) or the associated canaliculus 208, 210, to dilate The lacrimal implant 600 expands to a sufficient diameter upon implantation. In some examples, the second portion 606 tapers from a diameter at the proximal end of between about 0.50 millimeters to about 0.75 millimeters to a diameter of the dilator tip 654 of about 0.36 millimeters.

7A-7B illustrate yet another example of a lacrimal implant 700 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 700 can include an implant body 702 that includes a first portion 704 and a second portion 706 and can extend from a proximal end 708 of the first portion 704 to the second portion The distal end 710 of 706 . Proximal end 708 may define a longitudinal proximal axis 712 and distal end 710 may define a longitudinal distal axis 714 . The implant body 700 can be configured such that when implanted, there is an angled intersection of approximately 90 degrees between the proximal axis 712 and the distal axis 714 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ). As shown in the example of FIG. 7A , a smooth transition may be provided between the first portion 704 and the second portion 706 .

In this example, the implant body 702 includes a first lumen 718 configured to receive a first drug-releasing or other drug-releasing drug insert, the first cavity 718 being disposed at the implant Near the proximal end 708 of the object body first portion 704. Also in this example, the implant body 702 may include a graspable or other protrusion 732 , such as an annular protrusion, extending laterally from and completely around the proximal end 708 . In some examples, the graspable or other protrusions 732 include partially trimmed protrusions having a trimmed width of approximately 0.75 millimeters and extending around the proximal end 708 by varying amounts.

Figure 7B shows an example of a cross-sectional view of the lacrimal implant 700 taken along a line parallel to the longitudinal axis of the implant, for example along line 7B-7B of Figure 7A. As shown in FIG. 7B , the distal end 726 of the first portion 704 may be integral with the second portion 706 at or near the proximal end 728 of the second portion 706 . In various examples, the second portion 706 can include a longitudinal length measured from the proximal axis 712 to the distal end 710, the longitudinal length of the second portion 706 having a magnitude less than four times the longitudinal length of the first portion 704, The longitudinal length of the first portion 704 is measured from the proximal end 708 to the distal axis 714 . In some examples, the first portion can include a longitudinal length of about 1.5 millimeters and the second portion can include a longitudinal length of about 5 millimeters.

In various examples, the second portion 706 can include an integral dilator 750 to dilate anatomical tissue, such as one or both of the puncta 212, 214 or associated canaliculi 208, 210 (FIG. The lacrimal implant 700 expands to a sufficient diameter upon implantation. In some examples, the second portion 706 tapers from a diameter at the proximal end of approximately 0.46 millimeters to a diameter of the dilator tip 754 of approximately 0.36 millimeters.

8A-8B illustrate yet another example of a lacrimal implant 800 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, a lacrimal implant 800 can include an implant body 802 that includes a first portion 804 and a second portion 806 and can extend from a proximal end 808 of the first portion 804 to the second portion The distal end 810 of 806 . Proximal end 808 may define a longitudinal proximal axis 812 and distal end 810 may define a longitudinal distal axis 814 . The implant body 800 can be configured such that when implanted, there is an angled intersection of approximately 90 degrees between the proximal axis 812 and the distal axis 814 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ).

In this example, the proximal end 828 of the implant body second portion 806 can include a retaining element 856 configured to bias at least a portion of the ampulla 252 of the lacrimal canaliculus ( FIG. 2 ) when implanted. Retaining element 856 may include a recess 875 or other gripping means to aid insertion and/or removal of the implant. In this example, the implant body 802 includes a first lumen 818 configured to receive a first drug-releasing or other drug-releasing drug insert, the first cavity 818 being disposed at the implant Near the proximal end 808 of the first portion 804 of the object body. Also in this example, the implant body 802 may include a graspable or other protrusion 832 , such as an annular protrusion, extending laterally from and completely around the proximal end 808 . In some examples, the graspable or other protrusions 832 include partially trimmed protrusions that extend around the proximal end 808 by varying amounts.

Figure 8B shows an example of a cross-sectional view of the lacrimal implant 800 taken along a line parallel to the longitudinal axis of the implant, for example along line 8B-8B of Figure 8A. As shown in FIG. 8B , the distal end 826 of the first portion 804 may be integral with the second portion 806 at or near the proximal end 828 of the second portion 806 . In various examples, the second portion 806 can include a longitudinal length measured from the proximal axis 812 to the distal end 810, the longitudinal length of the second portion 806 being an amount less than four times the longitudinal length of the first portion 804, The longitudinal length of the first portion 804 is measured from the proximal end 808 to the distal axis 814 . In some examples, the first portion can include a longitudinal length of between about 1.725 millimeters and about 1.77 millimeters, and the second portion can include a longitudinal length of between about 4.77 millimeters and about 5 millimeters.

In various examples, the second portion 806 can include an integral dilator 850 to dilate anatomical tissue, such as one or both of the puncta 212, 214 or associated canaliculi 208, 210 (FIG. The lacrimal implant 800 expands to a sufficient diameter upon implantation. In certain examples, the second portion 806 tapers from a diameter of the proximal end 828 of approximately 0.46 millimeters to a diameter of the dilator tip 854 of approximately 0.36 millimeters.

FIG. 9 shows yet another example of a lacrimal implant 900 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, a lacrimal implant 900 can include an implant body 902 that includes a first portion 904 and a second portion 906 and can extend from a proximal end 908 of the first portion 904 to the second portion The distal end 910 of 906 . Proximal end 908 may define a longitudinal proximal axis 912 and distal end 910 may define a longitudinal distal axis 914 . The implant body 900 can be configured such that when implanted, there is an angled intersection of about 90 degrees between the proximal axis 912 and the distal axis 914 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ).

As shown, there may be a smooth transition between the first portion 904 and the second portion 906 . In this example, the smooth transition may include an insertion-assist recess 975 or other gripping means to aid in insertion and/or removal of the implant. Also in this embodiment, the implant body 902 may include a graspable or other protrusion 932 , such as an annular protrusion, extending laterally from and completely around the proximal end 908 . In some examples, the graspable or other protrusions 932 include partially trimmed protrusions that extend around the proximal end 908 by varying amounts.

10A-10B illustrate yet another example of a lacrimal implant 1000 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 1000 can include an implant body 1002 that includes a first portion 1004 and a second portion 1006 and can extend from a proximal end 1008 of the first portion 1004 to the second portion The distal end 1010 of 1006. Proximal end 1008 may define a longitudinal proximal axis 1012 and distal end 1010 may define a longitudinal distal axis 1014 . The lacrimal implant 1000 can be configured such that when implanted, there is an angled intersection of approximately 90 degrees between the proximal axis 1012 and the distal axis 1014 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ).

In this example, the proximal end 1028 of the implant body second portion 1006 can include a retaining element 1056 configured to bias at least a portion of the ampulla 252 of the canaliculus ( FIG. 2 ) when implanted. Retaining element 1056 may include insertion-assist recesses 1075 or other gripping means to aid in insertion and/or removal of the implant. In this example, the implant body 1002 includes a first cavity 1018 configured to receive a first drug-releasing or other drug-releasing drug insert, the first cavity 1018 being disposed at the implant Near the proximal end 1008 of the object body first portion 1004. Also in this example, the implant body 1002 can include a graspable or other protrusion 1032, such as an annular protrusion with a diameter of about 1.3 millimeters, which extends laterally from the proximal end 1008 and completely around the proximal end 1008. extended. In some examples, the graspable or other protrusions 1032 include partially trimmed protrusions that extend around the proximal end 1008 by varying amounts.

Figure 10B shows an example of a cross-sectional view of the lacrimal implant 1000 taken along a line parallel to the longitudinal axis of the implant, for example along line 10B-10B of Figure 10A. As shown in FIG. 10B , the distal end 1026 of the first portion 1004 may be integral with the second portion 1006 at or near the proximal end 1028 of the second portion 1006 . In various examples, the second portion 1006 can include a longitudinal length measured from the proximal axis 1012 to the distal end 1010, the longitudinal length of the second portion 1006 having a magnitude less than four times the longitudinal length of the first portion 1004, The longitudinal length of the first portion 1004 is measured from the proximal end 1008 to the distal axis 1014 . In some examples, the first portion can include a longitudinal length of about 1.5 millimeters and the second portion can include a longitudinal length of about 5 millimeters.

In various examples, the second portion 1006 can include an integral dilator 1050 to dilate anatomical tissue, such as one or both of the puncta 212, 214 or associated canaliculi 208, 210 (FIG. The lacrimal implant 1000 expands to a sufficient diameter upon implantation. In certain examples, the second portion 1006 tapers from a diameter of the proximal end 1028 of approximately 0.46 millimeters to a diameter of the dilator tip 1054 of approximately 0.36 millimeters.

11 to 17 show other lacrimal implants 1100, 1200, 1300, 1400, 1500, 1600, 1400, 1400, 1400, 1600, Example of 1700. In these examples, each lacrimal implant 1100, 1200, 1300, 1400, 1500, 1600, 1700 can include an implant body 1102, 1202, 1302, 1402, 1502, 1602, 1702 that 1102, 1202, 1302, 1402, 1502, 1602, 1702 respectively comprise a first part 1104, 1204, 1304, 1404, 1504, 1604, 1704 and a second part 1106, 1206, 1306, 1406, 1506, 1606, 1706, and may Extends from the proximal end 1108, 1208, 1308, 1408, 1508, 1608, 1708 of the first portion 1104, 1204, 1304, 1404, 1504, 1604, 1704 to the second portion 1106, 1206, 1306, 1406, 1506, 1606, 1706 1110, 1210, 1310, 1410, 1510, 1610, 1710 of the distal end. Each implant body 1102, 1202, 1302, 1402, 1502, 1602, 1702 may include at least one intermediately disposed retention protrusion 1192, 1292, 1392, 1492, 1592, 1692, 1792 to potentially further secure the lacrimal implant. implantation location. Centrally disposed retaining protrusions 1192, 1292, 1392, 1492, 1592, 1692, 1792 may be positioned on the implant body first portion 1104, 1204, 1304, 1404, 1504, 1604, 1704 and/or the implant body second portion 1106, 1206, 1306, 1406, 1506, 1606, 1706, and may take the form of annular, semi-annular, columnar or cylindrical protrusions. The centrally disposed retaining projections 1192, 1292, 1392, 1492, 1592, 1692, 1792 can comprise a cross-sectional dimension that is larger than the adjacent implant body portion and can slightly deform a portion of the canaliculus wall to provide additional fixity.

It is believed that occlusion of the lower canaliculus 210 , for example by a lacrimal implant, would result in back pressure within the canaliculus 210 , thereby pushing the implant away from the implantation site. It is believed that this back pressure may occur, for example, during blinking (when tear fluid is pumped down from the front surface of the eye to the drainage system) or during sneezing (when pressure is emitted from the pulmonary system). Accordingly, one or more of the additional retaining features, now shown as at least one intermediately disposed retaining protrusion 1192, 1292, 1392, 1492, 1592, 1692, 1792, may be used to prevent migration of the implant and further secure the implant. The location of the inserted lacrimal implant. These additional retaining features can be designed to prevent migration in the proximal direction without increasing the difficulty of implanting the implant.

18-19 show examples of other lacrimal implants 1800, 1900 that may be inserted through the punctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2). In these examples, each lacrimal implant 1800, 1900 can include an implant body 1802, 1902 that includes a first portion 1804, 1904 and a second portion 1806, 1906, and can be obtained from the second portion 1802, 1902. A proximal end 1808 , 1908 of one portion 1804 , 1904 extends to a distal end 1810 , 1910 of a second portion 1806 , 1906 . As shown, the intermediate portion 1896, 1996 of each implant body 1802, 1902 may be angled relative to one or both of the implant body first portion 1804, 1904 or the implant body second portion 1806, 1906 , to potentially further fixate the placement of the lacrimal implant.

It is believed that the angle of inclination of the intermediate portion 1896, 1996 can help capture the anatomy of the punctum 212, 214 and the canaliculus 208, 210 to maintain lacrimal gland implantation, for example, through directional force applied by angling against the canaliculus Object 1800, 1900 is in place for implantation. The directional force may be designed to continuously push against the feedback or other protrusion 1832 , 1932 flush with the puncta 212 , 214 .

FIG. 20 shows yet another example of a lacrimal implant 2000 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 2000 can include an implant body 2002 that includes a first portion 2004 and a second portion 2006 and can extend from a proximal end 2008 of the first portion 2004 to the second portion 2010 on the far end of 2006. Proximal end 2008 may define a longitudinal proximal axis 2012 and distal end 2010 may define a longitudinal distal axis 2014 . The implant body 2000 can be configured such that when implanted, there is an angled intersection of approximately 90 degrees between the proximal axis 2012 and the distal axis 2014 for biasing at least a portion of the implant body onto at least a portion of the canaliculus 208 , 210 ( FIG. 2 ) at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ). In various examples, the distal end 2026 of the first portion 2004 can be integral with the second portion 2006 at or near the proximal end 2028 of the second portion 2006 .

In this example, one or more material cuts 2080 are made in the outer surface of the implant body 2002 . As a result, the angled intersection between the proximal axis 2012 and the distal axis 2014 can become more linearly aligned during implantation, as shown in phantom, to facilitate insertion through the puncta 212, 214 and into the Associated canaliculus 208,210.

21A to 21B and 22A to 22B show examples of side views of other lacrimal implants 2100, 2200 that may be inserted through the punctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2). . In these examples, each lacrimal implant 2100, 2200 can include an implant body 2102, 2202 that includes a first portion 2104, 2204 and a second portion 2106, 2206, and can be obtained from the first portion 2102, 2206. A proximal end 2108 , 2208 of one portion 2104 , 2204 extends to a distal end 2110 , 2210 of a second portion 2106 , 2206 . Each second portion 2106, 2206 may include one or more arm members 2170, 2270 movable between a first configuration and a second configuration in which In the configuration, the one or more arm members 2170, 2270 are adjacent to the implant body, and in the second configuration, the one or more arm members 2170, 2270 extend laterally from one side of the implant body. In the first configuration, the one or more arm members 2170, 2270 facilitate insertion of the lacrimal implant through the punctum 212, 214 and into the associated canaliculus 208, 210 by providing a narrower profile. In the second configuration, the one or more arm members 2170 , 2270 extend laterally to fill at least one of the canaliculus ampulla 252 ( FIG. 2 ) or the canaliculi 208 , 210 when implanted. Optionally, one or more of the arm members 2170, 2270 may comprise a fluid swellable material, such as a hydrogel, to further secure the implanted lacrimal implant in the ampulla 252 or In the canaliculus 208,210.

In some examples, one or more arm members 2170 , 2270 may be incorporated into a mold that is also used to form the implant body 2102 , 2202 . One or more arm members 2170, 2270 may alternatively be attached to the existing implant body 2102, 2202 by molding or gluing. Different thicknesses and shapes may be employed for one or more of the arm members 2170, 2270 for different stiffness and fastening/removal characteristics. One or more arm members 2170, 2270 may be made of other materials than hydrogel, such as those used for haptics on intraocular lenses or the like.

23A-23B illustrate yet another example of a lacrimal implant 2300 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 2300 can include an implant body 2302 that includes a first portion 2304 and a second portion 2306 and can extend from a proximal end 2308 of the first portion 2304 to the second portion The distal end 2310 of 2306. The second portion 2306 can be at least partially surrounded by an expandable retention element (e.g., an inflatable balloon) 2372 configured to bias the second portion 2306 away from the tear when inflated. tubule wall.

In certain examples, the expandable retention element 2372 contains or can be inflated with a medicament to be delivered to the tissues of the eye or nasolarcimal system. In some examples, the expandable retention element 2372 may utilize one or more balloons separate from any drug insertion portion or other drug retention structure. The one or more balloons may optionally be similar to those used on balloon catheters, wherein an inflation lumen or the like is optionally included in the implant insertion tool to allow controlled inflation of the balloons . In such an example, a lacrimal implant 2300 may be inserted with the balloon deflated, as shown in Figure 23A. Once the lacrimal implant 2300 is in place, the balloon can then be inflated to secure the implant in place, as shown in Figure 23B.

The balloon may also be collapsible to allow for easier removal of the lacrimal implant 2300 . The balloon may optionally partially or fully conform to changes in size and shape of the canaliculus 208,210. An alternative example of a balloon may be inflated by swelling of a material disposed within the balloon, such as swelling of a hydrogel caused by water absorption through perforations or openings in the balloon. The one or more balloons may be an annular structure arranged about the supporting implant body, or may be arranged eccentrically about the axis of the implant body. As shown in FIG. 23B, the balloon may be disposed distally enough to be placed within or adjacent to the horizontal portion of the tear drainage channel, within or adjacent to the ampulla of the tear drainage system, or the like. Alternative examples may include one or more more proximal balloons.

FIG. 24A shows an example of a schematic view of yet another lacrimal implant 2400 implanted through the inferior punctum 214 and into the associated canaliculus 210 . The lacrimal implant 2400 can include an implant body 2402 that includes a first portion 2404 and a second portion 2406 . In various examples, the implant body 2402 can be configured such that when implanted, at least a portion of the implant body 2402 is biased to be located at or at a more distal end of the canalicular bend 250 At least a portion of the canaliculus 210 to securely maintain the implantation position of the implant 2400. In this example, second portion 2406 includes a longitudinal length of less than about 2 millimeters, eg, a dimension that is greater than the diameter of first portion 2404 but less than about 2 millimeters. Also in this example, the implant body 2402 can include a graspable or other protrusion 2432 that extends laterally, for example, at least partially around the proximal end of the implant body first portion 2404 .

25A-25B illustrate yet another example of a lacrimal implant 2500 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In these examples, the lacrimal implant 2500 can include an implant body 2502 that includes a first portion 2504 and a second portion 2506 and can extend from a proximal end 2508 of the first portion 2504 to the second portion The distal end 2510 of 2506. For example, the implant body can include a general shape that can generally match the anatomical components of the canaliculi 208, 210 to provide a comfortable and secure hold for the patient. Proximal end 2508 can define a longitudinal proximal axis 2512 and distal end 2510 can define a longitudinal distal axis 2514 . Implant body 2502 can be configured such that when implanting, there is an angled intersection between proximal end axis 2512 and distal end axis 2514 between 45 degrees and 90 degrees, for example, for placing the implant body At least a portion of 2502 is biased against at least a portion of the canaliculus 208 , 210 at or at the more distal end of the canaliculus bend 250 ( FIG. 2 ).

In the example of FIGS. 25A-25B , the implant body 2502 includes both a first lumen 2518 disposed near the proximal end 2508 and a second lumen 2520 disposed near the distal end 2510 . A first lumen 2518 extends inwardly from the proximal end 2508 of the first portion 2504 and a second lumen 2520 extends inwardly from the distal end 2510 of the second portion 2506 . A first drug-releasing or other drug-releasing drug insert may be disposed in the first cavity 2518 to provide sustained release of drug or other therapeutic agent to, for example, the eye, while a second drug-releasing drug insert may be positioned in the second cavity 2520. A drug-releasing or other drug-releasing drug insert to provide sustained release of drug or other therapeutic agent to the nasal passage or inner ear system. In some examples, the first lumen 2518 can extend inwardly from the proximal end 2508 of the first portion 2504 to a location near the distal end 2510 of the second portion 2506, such as shown in FIG. A drug-releasing or other drug-releasing drug insert is filled. In some examples, the second lumen 2520 can extend inwardly from the distal end 2510 of the second portion 2506 to a position near the proximal end 2508 of the first portion 2504, and the second lumen 2520 can be released with a second drug or other release agent. The medicine insertion part of the medicine is filled.

In some examples, the second portion 2506 includes an integral dilator 2550 to dilate anatomical tissue, such as one or both of the canaliculi 208, 210 and the puncta 212, 214, to accommodate the lacrimal implant 2500 when the lacrimal implant 2500 is implanted. Expand to a sufficient diameter. In this manner, the lacrimal implant 2500 can be implanted in ocular anatomy of various sizes without the need for pre-dilation via a separate enlargement tool. In these examples, integral dilator 2550 includes a generally concave shape relative to first portion 2504 . In some examples, the radius of the concave shape is less than the radius of the canaliculus bend 250 . In some examples, the radius of the concave shape is substantially the same as the radius of the canaliculus bend 250 . As shown in FIG. 25B , there may be a smooth transition between the first portion 2504 and the second portion 2506 .

In some examples, the proximal end 2528 of the implant body second portion 2506 can include a retaining element 2556 configured to bias at least a portion of the ampulla 252 of the lacrimal canaliculus ( FIG. 2 ) when implanted. In the example of FIG. 25A , retention element 2556 protrudes proximately from the intersection between implant body first portion 2504 and implant body second portion 2506 .

FIG. 26 shows yet another example of a lacrimal implant 2600 that may be inserted through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In these examples, the lacrimal implant 2600 includes an implant body 2602 that includes a first portion 2604 and a second portion 2606 and can extend from a proximal end 2608 of the first portion 2604 to the second portion 2606 The far end of 2610. Proximal end 2608 can define a longitudinal proximal axis 2612 and distal end 2610 can define a longitudinal distal axis 2614 . The implant body 2600 can be configured such that when implanted, there is an angled intersection between the proximal axis 2612 and the distal axis 2614 between 90 degrees and 135 degrees, for the implant body At least a portion is biased against at least a portion of the canaliculus 208 , 210 located at or at a more distal end of the canaliculus bend 250 ( FIG. 2 ).

In some examples, the implant body 2602 can include a first lumen 2618 disposed near the proximal end 2608 . In this example, the first lumen 2618 extends inwardly from the proximal end 2608 of the first portion 2604 to a location near the distal end 2610 of the second portion 2606 . In the first cavity 2618, for example, an insert of a first drug or other drug releasing agent may be disposed to provide prolonged release of the drug or other therapeutic agent to the eye, wherein the first drug or other drug releasing agent The insert that releases the agent has a volume of from about 0.2 cubic centimeters to about 0.25 cubic centimeters.

In some examples, the second portion 2606 includes an integral dilator 2650 to dilate anatomical tissue, such as one or both of the canaliculus 208, 210 and the punctum 212, 214, to accommodate the lacrimal implant 2600 during implantation. Expand to a sufficient diameter. In this way, the lacrimal implant 2600 can be implanted into ocular anatomy of various sizes without the need for pre-dilation via a separate enlargement tool. In this example, dilator 2650 includes a generally convex shape relative to first portion 2604 . In some examples, the radius of the convex shape is less than the radius of the canaliculus bend 250 . In some examples, the radius of the convex shape is substantially the same as the radius of the canaliculus bend 250 .

In some examples, the proximal end 2628 of the implant body second portion 2606 can include a retaining element 2656 configured to bias at least a portion of the ampulla of the lacrimal canaliculus 252 ( FIG. 2 ) when implanted. In this example, the retention element 2656 protrudes proximately from the intersection between the implant body first portion 2604 and the implant body second portion 2606 . In some examples, such as shown in FIGS. The glue retention element is configured to expand into the ampulla 252 when the implant body 2602 is implanted.

FIG. 27 shows an example of a side view of yet another lacrimal implant 2700 insertable through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, the lacrimal implant 2700 includes an implant body 2702 that includes a first portion and a second portion that are linear relative to each other prior to implantation. . The implant body 2702 extends from a proximal end 2708 of the first portion to a distal end 2710 of the second portion. Proximal end 2708 can define a longitudinal proximal axis 2712 and distal end 2710 can define a longitudinal distal axis 2714 . Implant body 2702 can be configured such that when implanting, there is an angled intersection of about 45 degrees to 135 degrees between proximal end axis 2712 and distal end axis 2714, for example, to be used for implant body 2702 At least a portion of the canaliculus 208, 210 ( FIG. 2 ) at or at a more distal end of the canaliculus bend 250 ( FIG. 2 ) is biased. In this example, the second portion of the implant body 2702 includes at least one undulation 2790 to help bias the implant body 2702 against the portion of the canaliculus 208 , 210 .

FIG. 28 shows an example of a side view of yet another lacrimal implant 2800 insertable through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, a lacrimal implant 2800 includes an implant body 2802 that includes a first portion and a second portion that are linear relative to each other prior to implantation. . The implant body 2802 extends from a proximal end 2808 of the first portion to a distal end 2810 of the second portion. Proximal end 2808 can define a longitudinal proximal axis 2812 and distal end 2810 can define a longitudinal distal axis 2814 . Implant body 2802 can be configured such that when implanted, there is an angled intersection of about 45 degrees to 135 degrees between proximal end axis 2812 and distal end axis 2814, for example, to be used for implant body 2802 At least a portion of the canaliculus 208, 210 ( FIG. 2 ) at or at a more distal end of the canaliculus bend 250 ( FIG. 2 ) is biased. In this example, the second portion of the implant body 2802 includes at least one intermediately disposed retention protrusion 2892, such as an annular rib-like protrusion. Keeping protrusion 2892 has the cross-sectional dimension greater than adjacent implant body parts, and can help the fixation of the implantation position of implant body 2802, and adjacent narrower implant body parts can help to implant The object body 2802 is biased against the portion of the canaliculus 208,210.

29 to 32 show examples of side views of other lacrimal implants 2900, 3000, 3100, 3200 that may be inserted through the punctum 212, 214 and into the associated canaliculus 208, 210 (FIG. 2). . In these examples, each lacrimal implant 2900, 3000, 3100, 3200 can include an implant body 2902, 3002, 3102, 3202 that includes a first portion 2904, 3004 , 3104, 3204 and second portion 2906, 3006, 3106, 3206 and may extend from the proximal end 2908, 3008, 3108, 3208 of the first portion 2904, 3004, 3104, 3204 to the second portion 2906, 3006, 3106, 3206 2910, 3010, 3110, 3210 of the distal end. Proximal ends 2908 , 3008 , 3108 , 3208 may define longitudinal proximal axes 2912 , 3012 , 3112 , 3212 .

The second portion 2906, 3006, 3106, 3206 can include a fluid swellable retention element 2994, 3094, 3194, 3294 configured to act as the implant body 2902, 3002, 3102 , 3202 expands laterally relative to the proximal axis 2912, 3012, 3112, 3212 when implanted. In various examples, the fluid swellable retaining elements 2994, 3094, 3194, 3294 can be formed such that either or both the direction of expansion or the amount of expansion can be controlled. For example, the fluid swellable retention elements 2994, 3094, 3194, 3294 may expand more in one plane than the other to securely anchor the lacrimal implant. In some examples, the fluid-swellable retaining element 2994, 3094, 3194, 3294 includes a portion that is configured relative to the proximal axis 2912, 3012, when the implant body is implanted. 3112, 3212 expand laterally in a direction away from the ampulla of the canaliculus 252 (FIG. 2). In some examples, as shown in FIGS. 29-30 , the fluid-swellable retaining element 2994, 3094, 3194, 3294 includes a portion that is configured to Distended laterally relative to the proximal axis 2912, 3012, 3112, 3212 in a direction toward the ampulla of the canaliculus 252 (FIG. 2).

In some examples, the fluid-swellable retaining elements 2994, 3094, 3194, 3294 can comprise hydrogels that can be inserted with a narrow profile through the punctum 212, 214 and into the associated In the lacrimal canaliculi 208,210. After insertion, the hydrogel or other fluid swellable retention element may bind water and expand into a wider configuration. A protrusion, such as at least one intermediately disposed retention protrusion 2992, 3092, 3192, 3292, may be used to retain the lacrimal implant in place of implantation as the hydrogel or other swellable element expands.

FIG. 33 shows an example of a side view of yet another lacrimal implant 3300 insertable through a punctum 212, 214 and into an associated canaliculus 208, 210 (FIG. 2). In this example, a lacrimal implant 3300 can include an implant body 3302 that includes a first portion 3304 and a second portion 3306, and a tear can extend from a proximal end 3308 of the first portion 3304 to a second portion. Distal end 3310 of portion 3306. As shown, the second portion 3306 may include an expandable retention element 3393 comprising coils, braids, stents, mesh tubes, sutures, thermoset polymers, thermoplastics, heat-activatable material or shape memory material. The expandable retention element 3393 can be configured to expand laterally relative to the proximal axis 3312 defined by the first portion 3304 when the implant is implanted. A protrusion, such as at least one intermediately disposed retention protrusion 3392, may be used to potentially further secure the implantation position of the lacrimal implant.

34A-34B show an example of a schematic diagram of yet another lacrimal implant 3400 and implant environment. In various examples, the implant body 3402 can include a graspable or other protrusion 3432, such as one or more protrusions extending at least partially laterally from or about the proximal end 3408 of the implant body first portion. In some examples, such as shown in FIG. 34B , protrusion 3432 can include a set of wings for insertion and removal of lacrimal implant 3400 into and out of the implantation site. This group of wings can be configured under the situation of consciously not feeling migration, and this is because the non-linear configuration of the implantation of implant body 3402 can be by adopting punctum bend 250 and optionally punctum ampulla 252 ( Figure 2) size or shape to prevent migration.

In the example of FIGS. 34A-34B , the one or more protrusions 3432 extend laterally in a direction parallel to the eye 100 or away from the eye 100 when implanted. In this way, the protrusion 3432 can still act as a graspable or feedback feature, but can limit patient discomfort when the lacrimal implant 3400 is implanted. In addition, the protrusion 3432 may not be buried in tissue by extending away from the eye 100, and may be easily identified by a patient or a physician. This may allow a user to quickly determine if the lacrimal implant 3400 remains in place without having to dig or search in the soft tissue surrounding the eye 100 . In some examples, a simple pull on the lower eyelid may expose protrusion 3432 pointing away from eye 100 . In the example of FIG. 34B , the lateral extension of the at least one protrusion 3432 from the proximal end 3408 is substantially in the same direction as the lateral extension of the second implant body portion relative to the distal end of the implant body first portion.

35-38 show examples of isometric views of various graspable protrusions or other grasping devices 3532, 3632, 3732, 3832 extending from the proximal end of a lacrimal implant 3500, 3600, 3700, 3800. The graspable or other protrusions 3532, 3632, 3732, 3832 can serve a variety of functions including: providing a structure that the user can grasp during implant insertion or removal; inhibiting or preventing the associated lacrimal implant from Puncta 212, 214 and associated canaliculi 208, 210 (FIG. 2) pass completely within; or are used to provide tactile or visual feedback to the user, eg, whether the implant is fully seated.

In some examples, as shown in FIG. 35, the graspable protrusion 3532 can include two or more expandable arm members sized to Rest on the outside of the punctum. The arm member may be secured to the implant body 3502, eg, via molding, adhesive, or welding. The expandable arm member is expandable to limit penetration of the lacrimal implant 3500 through the punctum 212,214 into the associated canaliculus 208,210. While two arm members are shown, some examples include more than two arm members, such as four arm members. The expandable arm members may exhibit an expanded profile separation distance 3505 corresponding to approximately twice the diameter of the implant body such that the proximal end of the proximal expandable arm member remains on the exterior of the punctum. The expandable arm member can be expanded in a variety of ways from a narrower profile configuration to an expanded profile configuration and can include coils, braids, sutures, thermoset polymers, thermoplastics, heat activated materials, nickel titanium At least one of alloy, shape memory material, polymer, polypropylene, polyester, nylon, natural fiber, stainless steel, polymethyl methacrylate, or polyimide. In some examples, after the lacrimal implant has been positioned in the canaliculus lumen 208, 210, the expandable arm member may be manually inflated, eg, by a physician.

In some examples, as shown in FIG. 36 , the graspable protrusion 3632 can comprise a loop of filaments embedded in the proximal end of the lacrimal implant 3600 to allow tensioning of the proximal end into a loop. The implant is then removed, for example, by means of tweezers. In some examples, the loop of filament assumes a purse handle-like shape that extends from the lacrimal implant having the loop to aid in removal of the lacrimal implant. The filaments may comprise at least one of heat activated material, nitinol, shape memory material, polymer, polypropylene, polyester, nylon, natural fiber, stainless steel, polymethyl methacrylate, or polyimide. In some examples, the filaments can include an absorbable thermoplastic polymer, such as at least one of polylactic acid (PLA), polyglycolic acid (PGA), or polylactic-glycolic acid (PLGA). The distal ends of the filaments can be embedded, molded, or otherwise secured to the implant body 3602 to secure the filaments to the lacrimal implant.

In some examples, as shown in FIG. 37 , the graspable protrusion 3732 can include at least one axially extending protrusion coupled to the implant body 3702 configured to bias the outermost portion of the lacrimal canaliculus 208 , 210 . external part. The interaction between the axially extending protrusion and the canaliculus inhibits over-insertion of the associated lacrimal implant 3700 due to natural constriction against the outward bias of the canaliculus.

In some examples, as shown in Figure 38, a longitudinal indentation, channel, or other groove 3832 in the implant body 3802 can be used in place of a graspable protrusion to allow insertion or removal of the lacrimal implant. 3800. The indentation, channel, or other groove 3832 may extend axially along only a portion of the implant body a sufficient distance to facilitate removal of the associated lacrimal implant. In a further example, the lacrimal implant may include a filament molded into the implant body and extending proximally for removal of the implant from the punctum.

Figures 39A-39B show examples of isometric views of drug insertion portion 322 and removal-assist filament 3999. In some examples, as shown in FIG. 39A , a filament 3999 can extend from the drug insertion portion 322 and be molded into it for removal purposes. In particular, filaments 3999 may comprise sutures, thermoset polymers, or shape memory alloys. In certain examples, as shown in FIG. 39B , a filament 3999 extends along the drug insertion portion 322 adjacent the implant body 3902 and is bonded to the distal end of the insertion portion for removal purposes. The filaments may be bonded to the distal end of the core insert by an adhesive such as cyanoacrylate, acrylic, epoxy, urethane, or hot melt adhesive.

40 is a block diagram illustrating an example of a method 4000 of making a lacrimal implant configured to be at least partially inserted through a punctum and into an associated canaliculus. At 4002, an implant body is formed extending from a proximal end of a first body portion to a distal end of a second body portion. In some examples, implant bodies are formed in various sizes to fit the patient's anatomy. In various examples, a proximal end is formed defining a proximal longitudinal axis, and a distal end is formed defining a distal longitudinal axis. The shaping of implant body can be configured so that when implanted, the proximal end axis and the distal end axis intersect at an angle of at least 45 degrees, to laterally bias at least a part of the implant body to be located at the canaliculus bend or On at least a portion of the canaliculus at the more distal end of the canaliculus bend.

In some examples, the second body portion is formed to include a dilator that generally narrows from a location near the proximal end of the second body portion to the distal end of the second body portion. In some examples, the dilator is formed by canting the outer surface of the second portion of the implant body at an angle of between about 1 degree and about 10 degrees relative to the longitudinal distal axis. In some examples, the outer surface of the second portion of the implant body is beveled to between about 0.2 mm and about 0.5 mm to the tip of the dilator.

In some examples, the implant body is formed to include a graspable or other protrusion extending laterally from the proximal end of the first body portion. In some examples, the protrusion is formed to be substantially aligned with respect to a direction of lateral extension of the first and second body portions. In some examples, the protrusion is formed such that when implanted, the protrusion extends laterally from the proximal end of the first body portion in a direction parallel to the eye or away from the eye.

At 4004, a drug insertion portion is disposed in at least one of the first body portion or the second body portion. In various examples, the drug insertion portion is positioned such that the exposed drug insertion portion surface sits adjacent to at least one of the proximal or distal ends for delivering medication or other therapy to, for example, the eye, nasal passages, or inner ear Sustained release of pharmaceuticals. In some examples, the first drug insertion portion is disposed in the first body portion and the second drug insertion portion is disposed in the second body portion. In various examples, one or more of the drug inserts includes a drug core that includes a drug or other therapeutic agent.

At 4006, the outer surface portion of the implant body is coated with at least one of a fluid swellable material, a lubricious coating, or an antimicrobial coating. In various examples, portions of the outer surface of the implant body are polished using a polishing process.

sheath example

The sheath can comprise appropriate shapes and materials in a variety of ways to control the migration of drugs or other therapeutic agents from the drug insertion portion. In some examples, the sheath is configured to conform to the anatomy of the implant, such as the anatomy of the punctum or associated canaliculus. As noted above, in some examples, the sheath at least partially covers or surrounds the drug insertion portion and can snugly fit the outer surface of the matrix/medicament mixture. The sheath can be made of a material that is substantially impermeable to the drug or other therapeutic agent such that the rate of migration of the drug or therapeutic agent is controlled primarily by the exposed surface area of the drug insertion portion not covered by the sheath. In many examples, the migration of the medicament through the sheath may be about one-tenth or less than the migration of the medicament through the exposed surface of the drug insertion portion. Suitable sheath materials may include polyimide, polyethylene terephthalate (PET), among others. The sheath body may comprise a thickness of about 0.00025 inches to about 0.0015 inches defined from a sheath surface adjacent the surface of the exogenous matrix/agent mixture to an opposite sheath surface remote from the outer surface. The overall diameter of the sheath across the drug insertion portion is in the range of about 0.2 mm to about 1.2 mm. The drug insertion portion can be formed by impregnating a matrix in the sheath. In some examples, the sheath may include a tube that introduces the matrix/agent mixture. The sheath may also be impregnated around the matrix/agent mixture, eg around a pre-formed matrix/agent core.

The sheath may be provided with one or more additional components, for example to aid in the clinical use of the lacrimal implants described herein. For example, the sheath can receive a drug insertion portion that can be exchanged in situ while the implant body remains implanted in the patient's body or after its removal. In some examples, the sheath may be provided with one or more external protrusions that apply a force to the sheath when squeezed, which causes the matrix/agent mixture to eject from the sheath. A replacement drug insert can then be positioned in the sheath.

Examples of Healing Potions

Therapeutic agents (or simply referred to as "medicaments") may especially include drugs made of any one or any combination of the following substances or their equivalents, derivatives, or analogs, including: anti-glaucoma drugs (such as , adrenergic agonists, adrenergic antagonists (beta-blockers), carbonic anhydrase inhibitors (CAIs, systemic and topical), parasympathomimetics, prostaglandins, and hypotensive lipids and combinations thereof); antibacterial agents (e.g., antibiotics, antivirals, antiparacytics, antifungals, etc.); corticosteroids or other anti-inflammatory agents (e.g., NSAIDs or other analgesics and pain treatment compounds ); decongestants (eg, vasoconstrictors); prophylactics to reduce allergic reactions (eg, antihistamines, cytokine inhibitors, leukotriene inhibitors, IgE inhibitors, immunomodulators); mast cell stabilizers Mast cell stabilizer; Cycloplegic; Mydriatic dilator or the like.

Exemplary useful agents include, but are not limited to: thrombin inhibitors; antithrombotics; thrombolytics; fibrinolytics; vasospasm inhibitors; vasodilators; antihypertensives; Tetracycline, aureomycin, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamicin erythromycin, penicillin, sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodium propionate), antifungals (eg, amphotericin B and miconazole ) and antivirals (eg, idoxuridine trifluorothymidine, acyclovir, gancyclovir, interferon); inhibitors of surface glycoprotein receptors; antiplatelet agents; antimitotic agents Drugs; Microtubule Inhibitors; Antisecretory Agents; Activity Inhibitors; Remodeling Inhibitors; Antisense Nucleotides; Antimetabolic Agents; Antiproliferative Agents (including Antiangiogenic Agents); Anticancer Chemotherapeutic Agents Anti-inflammatory agents (eg, hydrocortisone, hydrocortisone acetate, dexamethasone 21-phosphate, fluocinolone, medrison, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate , fluorometholone, betamethasone, triamcinolone, triamcinolone acetonide); non-steroidal anti-inflammatory drugs (NSAIDs) (such as salicylates, indomethacin, ibuprofen, diclofenac, flurbiprofen, piroxicam, indomethacin, ibuprofen, naxopren, piroxicam, and nabumetone). Examples of such anti-inflammatory steroids contemplated for use in the methods of the invention include triamcinolone acetonide (generic name) and corticosteroids including, for example, triamcinolone, dexamethasone, fluocinolone, cortisone, prednisolone, Flumetholone and its derivatives; antiallergic drugs (such as sodium chromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine, pyrilamine , pheniramine); antiproliferative agents (eg, 1,3-cis retinoic acid, 5-fluorouracil, paclitaxel, rapamycin, mitomycin C, and cisplatin) decongestants (e.g., phenylephrine, naphazoline, tetrahydrozoline); miotics and anticholinesterases (e.g., pilocarpine, salicylates, carbacholine, acetylcholine chloride, fenugreek base, ecerin, isoforphos, phospholine iodide, demebroxam); antineoplastic agents (e.g., carmustine, cisplatin, fluorouracil3); immunological agents (e.g., vaccines and immunostimulatory hormones (eg, estrogen, beta-estradiol, progestational, progesterone, insulin, calcitonin, parathyroid hormone, peptides, and vasopressin hypothalamus releasing factor) ; immunosuppressants, growth hormone antagonists, growth factors (e.g., epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor beta, growth hormone, fibronectin); angiogenesis inhibitors (e.g., angiogenesis somatostatin, anecortave acetate, thrombin, anti-VEGF antibody); dopamine agonist; radiotherapeutic agent; peptide; protein; enzyme; extracellular matrix; component; ACE inhibitor; free chelating agents; antioxidants; antipolymerases; photodynamic therapy agents; gene therapy agents; and other therapeutic agents such as prostaglandins, antiprostaglandins, prostaglandin precursors, including antiglaucoma agents, the Antiglaucoma drugs include beta-blockers such as timolol, betasolol, levobunolol, atenolol, and prostaglandin analogs such as bimatoprost, travoprost, latanoprost carbonic anhydrase inhibitors such as acetazolamide, dorzolamide, brinzolamide, methazolamide, diclofenamide, damus; neuroprotective agents such as lubeluzole, nimodipine and Its related compounds; and parasympathomimetic drugs such as pilocarpine, carbachol, physostigmine, etc.

Additional agents that can be used with the lacrimal implants of the present invention include, but are not limited to, drugs that have been approved under the United States Federal Food, Drug, and Cosmetic Act, Section 505 or under the Public Health Service Act, which Some of them can be found in the website http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index of US Food and Drug Administration (FDA). The lacrimal implants of the present invention may also be used with drugs listed in the Orange Book (Orange Book), either paper or electronic, which can be found on the FDA Orange Book website ( http://www. .fda.gov/cder/ob/ ), and the Orange Book has or records the same, earlier, or later date as the filing date of this patent document. For example, these drugs may include, inter alia, dorzolamide, olopatadine, travoprost, bimatoprost, cyclosporine, brimonidine, moxifloxacin, tobramycin, brinzolamide, Aciclovir timolol, ketorolac, ketorolac tromethamine, dehydrocortisol acetate, sodium hyaluronate, nepafenac, bromfenac sodium, diclofenac, flurbiprofen, suprofen (suprofenac), binoxan, patanol, dexamethasone/tobramycin combination, moxifloxacin, or acyclovir.

Examples of diseases or conditions that may be treated with the agents listed above include, but are not limited to, glaucoma, pre- and post-operative eye treatments, dry eye and anti-ocular allergies, anti-infection, post-operative inflammation or ailments, respiratory-related conditions such as allergies disorders of the inner ear such as dizziness or migraine, or other systemic disorders such as high blood pressure cholesterol, steroid therapy, pulmonary disorders or immune disorders. In some examples, the therapeutic agent may include a lubricant or surfactant, such as a lubricant to treat dry eye. In other examples, the therapeutic agent may include an absorbent capable of absorbing tear fluid from the eye.

Example of drug insertion part

The drug insert may include one or more drugs or other therapeutic agents, and in some instances, one or more matrix materials to provide sustained release of the drugs or other agents. One or more drugs or other therapeutic agents may migrate from the exposed surface of the drug insert to the target tissue (eg, the ciliary muscle of the eye) based at least in part on the solubility of the drugs or agents in the matrix. The rate of migration of the drug or agent from the exposed surface can also be related to the concentration of the drug or agent dissolved in the matrix. In some examples, the concentration of the drug or agent dissolved in the drug insert can be controlled to provide a desired release rate of the drug or agent. Additionally or in combination, the rate of migration of the drug or agent from the exposed surface may be related to one or more properties of the matrix in which the drug or agent is dissolved, such as the properties of a silicone matrix formulation. In some examples, the drug or agent contained in the drug insert may comprise liquid, solid, solid gel, solid crystalline, solid amorphous, solid particulate, or dissolved form. In one such example, liquid latanoprost droplets or solid bimatoprost particles are dispersed in a silicone matrix.

The drug insert may comprise one or more biocompatible materials capable of providing sustained release of the one or more drugs or agents. Although the drug insert is discussed above primarily with respect to the example of inclusions comprising a substantially non-biodegradable silicone matrix with a drug or agent soluble therein, the drug insert may include other structures that provide sustained release of the drug or agent , such as a biodegradable matrix, a porous drug insert, a liquid drug insert or a solid drug insert. The matrix including the drug or agent may be formed from a biodegradable polymer or a non-biodegradable polymer. In some examples, the non-biodegradable drug insert may comprise silicone, acrylate, polyethylene, polyurethane, polyurethane, hydrogel, polyester (e.g., from E.I.D. DACEON.RTM. from Pont de Nemours and Company), polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyetheretherketone (PEEK), nylon, extruded collagen, polymer foam, silicon Ketone rubber, polyethylene terephthalate, ultra-high molecular weight polyethylene, polyethyleneurethane, polyurethane, polyimide, stainless steel, nickel-titanium alloys (such as nitinol), titanium, stainless steel , cobalt-chromium alloys (eg, ELGILOY.RTM. available from Elgin Specialty Metals, Elgin, Illinois; CONICHROME.RTM. available from Carpenter Metals, Wyomissing, Pennsylvania). In some examples, the biodegradable drug insert may comprise one or more biodegradable polymers such as proteins, hydrogels, 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 acid), polydioxanone , polyacetate lactone, polygluconate, polylactic acid-polyethylene oxide copolymer, modified cellulose, collagen, polyorthoester, polyhydroxybutyrate, polyanhydride, polyphosphate, poly(α -hydroxy acids) and combinations thereof. In some embodiments, the drug insertion portion can comprise at least one hydrogel polymer.

end note

In particular, lacrimal implants and related methods for providing fixed retention within the puncta and canaliculi of the eye are discussed herein. The lacrimal implant may include an implant body configured for insertion at least partially through the punctum and into the canaliculus. The implant body may include a first portion and a second portion, and may extend from a proximal end of the first portion defining a longitudinal proximal axis to a distal end of the second portion defining a longitudinal distal axis. The implant body may be configured such that there is an angled intersection between the proximal and distal axes of at least 45 degrees when implanted using the integral dilator. Like this, at least a portion of the implant body can be biased onto at least a portion of the canaliculus at or at the far end of the canaliculus flexure, thereby using the anatomical structure to maintain the implantation of the lacrimal implant. into position. In various examples, the lacrimal implant may further include a drug insertion portion disposed in at least one of the first portion or the second portion of the implant body to provide access to, for example, the eye, nasal passage, or The inner ear system provides sustained release of drugs or other therapeutic agents.

Advantageously, in some instances, the lacrimal implants of the present invention can successfully block the flow of tears or the flow of tears to the eyes, nasal passages, inner ear, etc. over varying periods of time, such as from days to months to years. Sustained release of drugs or other therapeutic agents is provided. Additionally, by including first and second implant body lumens, it is possible to have dual drug or other drug release profiles. For example, two separate drugs can be released from two different implant locations. In addition, the lacrimal canaliculus retaining structure of the implant body of the present invention can reduce excessive elongation of the punctum and lacrimal canalus and inadvertent dropping of the implant. Even further, when an expandable covering or other expandable retention member can be applied to the implant body, such as an outer surface portion of the implant body, to fit within hollow tissue structures of varying dimensions, the present invention Lacrimal implants can be implanted to provide a one-size-fits-all (or many) approach. The lacrimal implant of the present invention may also be better tolerated by the patient due to, for example, the orientation of the graspable or other protrusions at the proximal end of the implant body.

The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments may also be referred to herein as "examples." All publications, patents, patent documents referred to in this document are hereby incorporated by reference in their entirety as if each were incorporated by reference. In the event of conflicting usages between this document and those incorporated by reference, the usages in one or more of the included references should be considered supplementary to those of this document; for irreconcilable conflicts , the usage control in this paper.

In this document, the term "a" is used as commonly used in patent documents to include one or more than one, regardless of other examples or usage of "at least one" or "one or more". In this document, the term "or" is used to mean a non-exclusive such that "A or B" includes "A but not B", "B but not A" and "A and B", unless otherwise indicated. In this document, the term "about" is used to refer to an amount that is about, approximately, almost, or around equal to the stated amount.

In this document, the term "proximal" refers to the position closer to the hand of the physician who implants the lacrimal implant in the patient, and the term "distal" refers to the location, especially when the implant is implanted in the patient. position farther from the doctor's hand during the procedure.

The term "hydrogel" is used to refer to absorbent or other retaining materials (eg, absorbent materials), such as superabsorbent polymers, hydrocolloids, and water-absorbing hydrophilic polymers. In certain instances, the term "hydrogel" refers to superabsorbent polymer particles in a "dry" state, more specifically, by weight, from particles that contain no water to particles that contain less water than the weight of the particle, e.g. less than 5%. In certain examples, the term "hydrogel" refers to a superabsorbent polymer in a "dry" state when the hydrogel is not swellable and refers to its hydrated or swollen state, more specifically, has absorbed A hydrogel that contains at least, for example, several times the weight of water. As the hydrogel material absorbs fluid, the hydrogel may increase in size (swell) and its shape may change to bias, for example, the ampulla of the canaliculus or at least a portion of the canaliculus wall.

In the appended claims, the terms "comprising" and "wherein" are used as the plain English equivalents of the respective terms "comprising" and "wherein". Moreover, in the following claims, the terms "comprises" and "comprising" are expandable, i.e., systems, components, means that include elements other than those listed after such term in the claims , articles or processes are still considered to fall within the scope of the claims. Furthermore, in the following claims, the terms "first", "second", and third", etc. are used for labeling purposes only and are not intended to impose numerical requirements on their purpose.

The foregoing description is intended to be illustrative rather than restrictive. For example, the examples (or one or more features) described above may be used in combination with each other. Other examples may be used by those skilled in the art upon reviewing the above description, for example. Furthermore, in the foregoing Detailed Description, various features may be grouped together to simplify the disclosure. This should not be interpreted as implying that an unclaimed disclosed feature is essential to any claim. Rather, inventive inventiveness may lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. The scope of the invention should be determined with reference to the appended claims, along with the full range of equivalents to which such claims are entitled.

The Abstract is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is to be obeyed with the understanding that this Abstract shall not be used to interpret or limit the scope or meaning of the claims.

Claims (39)

1. can be inserted into the lacrimal implants in lacrimal ductule, described lacrimal implants comprises:

Implant body, described implant body comprises Part I and Part II, the far-end of described implant body from the proximal extension of described Part I to described Part II;

The near-end of described Part I limits longitudinal near-end axis, and the far-end of described Part II limits longitudinal far-end axis;

Described Part I comprises the chamber extended internally from the near-end of described Part I and the medicine insertion section arranged the described chamber of described Part I, thus provides the slow release of medicine or other healing potion to eyes,

Described implant body configuration become to make when planted in described lacrimal ductule time, between described longitudinal near-end axis with described longitudinal far-end axis, have angled the intersection, be positioned at going up at least partially compared with the described dacryocanalicular of far-end of lacrimal ductule bending section place or described lacrimal ductule bending section for by being biased at least partially of described implant body;

Wherein, the longitudinal length of the Part II of described implant body has the value of four times of the longitudinal length of the Part I being less than described implant body, and

The near-end of wherein said Part II comprises holding element, and described holding element to be configured to when described implant body is implanted bias voltage ampulla of lacrimal ductule at least partially.

2. lacrimal implants according to claim 1, wherein, described implant body configuration becomes to make between described longitudinal near-end axis with described longitudinal far-end axis, to have angled the intersection before being implanted in described lacrimal ductule.

3. lacrimal implants according to claim 1 and 2, wherein, described implant body configuration becomes partially or fully suppression fluid to flow into and flows through described lacrimal ductule.

4. lacrimal implants according to claim 1, wherein, the far-end of described Part I is integral with described Part II near the near-end of the proximal end of described Part II or described Part II.

5. lacrimal implants according to claim 1, wherein, one or two in described Part I and described Part II comprise the additional holding element that the fluid that is configured to expand can be swelling.

6. lacrimal implants according to claim 5, wherein, described Part II comprises the swelling additional holding element of described fluid energy, and longitudinal near-end axis that the additional holding element that described fluid can be swelling is configured to when described implant body is implanted relative to described Part I laterally expands.

7. lacrimal implants according to claim 6, wherein, the additional holding element that described fluid can be swelling comprises the part being configured to laterally expand along the direction away from ampulla of lacrimal ductule when described implant body is implanted.

8. the lacrimal implants according to claim 6 or 7, wherein, the additional holding element that described fluid can be swelling comprises the part being configured to laterally expand along the direction towards ampulla of lacrimal ductule when described implant body is implanted.

9. lacrimal implants according to claim 1, wherein, described Part II comprises additional holding element, described additional holding element is the holding element that can expand, the described holding element that can expand comprises at least one in coil, fabric, support, webmaster, suture, thermosetting polymer, thermoplastic, the heat activated material of energy and shape-memory material, the described holding element that can expand is configured to laterally expand when described implant body is implanted, to form described angled intersection.

10. lacrimal implants according to claim 1, the additional holding element that what the described lacrimal implants part comprised around described Part II was arranged can expand, the described additional holding element that can expand is configured to when expanding away from Part II described in described dacryocanalicular wall bias voltage.

11. lacrimal implants according to claim 1, wherein, described Part II comprises the arm member that can move between the first structure and second construct;

Described arm member can be arranged along described implant body in described first structure, for being inserted in described lacrimal ductule, and laterally can extend from the side of described implant body in described second structure.

12. lacrimal implants according to claim 1, wherein, described Part II comprises the dilator of one, the dilator of described one narrows from the position of the near proximal ends of described Part II to the far-end of described Part II generally, so that be implanted in described lacrimal ductule by described implant body.

13. lacrimal implants according to claim 12, wherein, the diameter at the dilator tip of one is between 0.2 millimeter and 0.5 millimeter.

14. lacrimal implants according to claim 12 or 13, wherein, the dilator of the described one of the far-end measuring from the position of the near proximal ends of described Part II to described Part II be 1 degree and 10 degree relative to the outer surface angle of inclination of described longitudinal far-end axis.

15. lacrimal implants according to claim 1, wherein, described Part II comprises at least one fluctuation portion.

16. lacrimal implants according to claim 1, wherein, at least one in described Part I and described Part II comprises projection that the is annular of at least one intermediate arrangement, semiorbicular, column or tubular, and the projection of described intermediate arrangement has the cross sectional dimensions being greater than adjacent implant body part.

17. lacrimal implants according to claim 1, described lacrimal implants comprises at least in part from the projection that can firmly grasp of the proximal extension of described Part I, and the described pop-up structure that can firmly grasp becomes to take a seat against lacrimal point or near described lacrimal point when described implant body is implanted.

18. lacrimal implants according to claim 17, wherein, when described implant body is implanted, the described projection that can firmly grasp from the near-end of described Part I along row at eye level or direction away from eye laterally extend.

19. lacrimal implants according to claim 1, wherein, it is at least 45 to spend that described angled between described longitudinal near-end axis with described longitudinal far-end axis is intersected.

20. lacrimal implants according to claim 1, wherein, described lacrimal implants is used for treating oculopathy.

21. lacrimal implants according to claim 1, wherein, described lacrimal implants is used for treating and breathing relevant disease.

22. lacrimal implants according to claim 1, wherein, described lacrimal implants is used for treating inner ear disorders.

23. 1 kinds for being inserted into the lacrimal implants in lacrimal ductule, described lacrimal implants comprises:

Implant body, described implant body non-linearly extends to the distal portions that can be positioned in described dacryocanalicular horizontal segment from the proximal part that can be positioned in described dacryocanalicular vertical section, and has mid portion between which;

The the first medicine insertion section being arranged on the chamber in described proximal part and arranging in the described chamber of described proximal part, thus the slow release of medicine or other healing potion is provided to eyes,

Described mid portion partly extends along the first direction towards described proximal part and partly extends along the second direction towards described distal portions, when being implanted in described lacrimal ductule with box lunch, ground, described implant body direction laterally bias voltage is positioned at described at least partially dacryocanalicular compared with far-end of lacrimal ductule bending section place or described lacrimal ductule bending section; And

Wherein, described implant body suppression fluid flows into and flows through described lacrimal ductule,

Wherein, when described implant body is implanted, described mid portion partly extends along the third direction substantially contrary with described second direction towards ampulla of lacrimal ductule.

24. lacrimal implants according to claim 23, wherein, the longitudinal length that can be positioned at the described implant body in described dacryocanalicular vertical section is less than four times of the longitudinal length of the described implant body that can be positioned in described dacryocanalicular horizontal segment.

25. lacrimal implants according to claim 23 or 24, wherein, the first direction extension of described mid portion is the angle between 45 degree and 135 degree relative to the second direction extension of described mid portion.

26. lacrimal implants according to claim 23, wherein, described second direction extension comprises longitudinal dilator, and described longitudinal dilator has roughly recessed shape relative to described first direction extension; And wherein, the radius of described roughly recessed shape is less than the radius of described lacrimal ductule bending section.

27. lacrimal implants according to claim 23, wherein, described second direction extension comprises longitudinal dilator, and described longitudinal dilator has roughly convex shape relative to described first direction extension.

28. lacrimal implants according to claim 23, wherein, described second direction extension comprises longitudinal dilator, and described longitudinal dilator has the axis substantially vertical with the axis of described first direction extension.

29. lacrimal implants according to claim 23, wherein, at least one in described proximal part and described distal portions comprises projection that the is annular of at least one intermediate arrangement, semiorbicular, column or tubular, and the projection of described intermediate arrangement has the cross sectional dimensions being greater than adjacent implant body part.

30. lacrimal implants according to claim 23, described lacrimal implants comprises the projection that can firmly grasp, and the described projection that can firmly grasp laterally extends from described proximal part.

31. lacrimal implants according to claim 23, described lacrimal implants comprises the material that fluid in the outer surface part being arranged in described implant body can be swelling, and the material structure that described fluid can be swelling becomes to expand when implanted the outer surface diameter part of described implant body.

32. lacrimal implants according to claim 23, described lacrimal implants comprises the second medicine insertion section, described second medicine insertion section is arranged in described distal portions, one or two suppression fluid in described first medicine insertion section and the second medicine insertion section flows through described implant body, and comprises the exposed surface that at least one is configured to carry slow release.

33. lacrimal implants according to claim 32, described lacrimal implants comprises the chamber being arranged in described distal portions, chamber in described distal portions is configured to the described second medicine insertion section holding medicated core form, and described medicated core comprises the second medicament being configured to treat to be received by nasal passage.

34. 1 kinds of manufactures can be inserted into the method for the lacrimal implants in lacrimal ductule, and described method comprises:

Form implant body, described implant body, from the proximal extension of the first noumenon part to the far-end of the second body part, comprising:

Described second body part is made to extend the longitudinal length being less than four times of the longitudinal length of described the first noumenon part;

Construct described near-end and described far-end, longitudinal near-end axis and longitudinal far-end axis is limited respectively when being implanted in described lacrimal ductule with box lunch, described longitudinal near-end axis and longitudinal far-end axis intersect at angle, make described implant body configuration become ground, direction transverse bias to be positioned at described at least partially dacryocanalicular compared with far-end of lacrimal ductule bending section place or described lacrimal ductule bending section; With

Arrange at least one in the first medicine insertion section in described the first noumenon part and the second medicine insertion section in described second body part, comprise at least one in the location exposed surface of described first medicine insertion section adjacent with described near-end and the exposed surface of the described second medicine insertion section adjacent with described far-end, to provide the slow release of the first medicament or the second medicament respectively, and

The near-end of wherein said second body part comprises holding element, and described holding element to be configured to when described implant body is implanted bias voltage ampulla of lacrimal ductule at least partially.

35. methods according to claim 34, wherein, one or two being formed in described the first noumenon part and described second body part comprise projection that is that form the annular of at least one intermediate arrangement, semiorbicular, column or tubular, and the projection of described intermediate arrangement has the cross sectional dimensions being greater than adjacent implant body part.

36. methods according to claim 34 or 35, wherein, form described second body part and comprise formation dilator, described dilator narrows from the position of the near proximal ends of described second body part to the far-end of described second body part generally.

37. methods according to claim 36, wherein, form described dilator and comprise the outer surface angle of inclination relative to described longitudinal far-end axis forming described implant body, the far-end measuring of outer surface angle of inclination from the position of the near proximal ends of described second body part to described second body part of described implant body is 1 degree and 10 degree.

38. methods according to claim 34, wherein, form proximate distal ends that described second body part is included in described the first noumenon part and arrange that fluid can swelling holding element, comprise and described fluid can be arranged so that the lateral expansion cage structure relative to described longitudinal near-end axis of the holding element that described fluid can be swelling to become when described implant body is implanted lacrimal ductule or ampulla of lacrimal ductule anatomical structure described in bias voltage at least partially by swelling holding element.

39. methods according to claim 34, described method comprises the outer surface part of implant body described in the swelling coated materials of use fluid energy.