WO2021210005A1

WO2021210005A1 - Apparatus for suprachoroidal delivery and uses thereof

Info

Publication number: WO2021210005A1
Application number: PCT/IN2020/050489
Authority: WO
Inventors: Ajay Aurora
Original assignee: Ajay Aurora
Priority date: 2020-04-17
Filing date: 2020-06-02
Publication date: 2021-10-21

Abstract

The present invention provides an apparatus (100) capable of resting over the surface of the eye for suprachoroidal delivery of at least a substance comprising: (a) a lumenal needle sleeve (102) comprising a proximal end and a distal end, wherein the distal end of the sleeve removably accommodates a needle; and (b) a wedge base (104) for supporting the luminal needle sleeve, the wedge base comprising at least five (5) surfaces, wherein the wedge base supports the lumenal needle sleeve such that the needle sleeve is inclined at an angle in the range of 5° to 50° relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera. The apparatus (100) can accommodate commercially available hypodermic needle for injection and facilitates ease and accuracy of suprachoroidal drug delivery.

Description

APPARATUS FOR SUPRACHOROIDAL DELIVERY AND USES THEREOF

FIELD OF INVENTION

The present invention generally relates to the field of biomedical devices. In particular, the invention relates to a device for assisting suprachoroidal drug delivery.

BACKGROUND OF THE INVENTION

Treatment of diseases of the posterior segment of the eye such as choroidal neovascularization, macular oedema presents a major challenge in ophthalmology. The posterior segment of the eye, including the retina, choroid, macula, and optic nerve are difficult to access due to their location such that the medications applied topically or given by injection in the subconjunctival or subtenon space do not reach in adequate concentration due to the blood retinal and blood ocular barrier.

Current drug delivery techniques to access the posterior segment of the eye include intra- vitreal injections, peri-ocular injections (i.e., subconjunctival, subtenon), and intra-vitreal implants. Drug delivery by injection into the suprachoroidal space is another technique that has recently been proposed in the treatment of posterior segment disease. The suprachoroidal space provides a potential route of access to the posterior segment from the anterior region of the eye.

Intravitreal injections deliver drugs into the vitreous cavity. The drug travels through the retina and affects the retina and choroid. This drug may affect the lens, causing cataract and exit the vitreous through the trabecular meshwork producing glaucoma.

The SCS (Suprachoroidal space) is a potential space bound by the ciliary body anteriorly, Optic nerve posteriorly, choroid internally and sclera externally. It is a potential space that can expand with the introduction of drug formulation. Hence fewer ocular side effects are expected due to dose sparing and also because drugs are compartmentalized away from non-target tissues (e.g., lens hence cataract avoided and Trabecular meshwork, hence glaucoma avoided). At present, drugs and other substances can be delivered in the SCS by two methods: (1) surgical methods such as (a) Olive tipped cannula: Needs a large scleral incision under anaesthesia and insertion of a large cannula to deliver substances in the suprachoroidal space; (b) Microcatheter: For inserting the microcatheter, SCS is dissected through the sclera (Sclerotomy) under anaesthesia using a scalpel that cuts through full thickness of sclera. Once the sclerochoroidal junction is identified, slow and delicate dissection is done to avoid damage to the underlying tissues and a blunt-tipped catheter is tunnelled through the SCS towards the posterior pole. Catheter tip is identified by a flashing diode light. After the drug infusion to the intended site the catheter is gently removed and the Sclerotomy closed. The benefits of accessing the SCS via incision and catheterization is that the site of drug delivery can be visualized and chosen by the ophthalmologist but has its potential risks of a surgical manoeuvre and possible damage to the underlying tissue while negotiating the catheter. (2) non-surgical: microneedles without need for sclerotomy; This technology, under further development and evaluation by Clearside Biomedical, uses a very special microneedle of 900 pm or 1100 pm total length with extremely short bevel (about S00 pm). The drug is loaded into the device and the needle is pressed perpendicularly to the sclera firmly producing a dimple. The drug is then injected. The system uses a proprietary microneedle that is not available commercially and hence increases the cost. It injects the drug perpendicular to the sclera which may lead to leakage of the drug along the shaft of the needle outside the eye.

Therefore, there is a need in the art to develop novel systems which are cheap, and compatible with existing delivery systems, such as standard gauge needles, while at the same time increasing accuracy and efficiency of drug delivery methods into the suprachoroidal space.

OBJECTS OF THE INVENTION

An object of the present invention is to provide an apparatus for suprachoroidal delivery of a substance which allows for use of standard hypodermic needles for substance delivery.

Another object of the present invention is to provide an apparatus for suprachoroidal delivery of a substance in a cheap and efficient manner.

SUMMARY OF THE INVENTION

In an aspect of the present invention, there is provided an apparatus capable of resting over the surface of the eye for suprachoroidal delivery of at least a substance comprising: (a) a lumenal needle sleeve comprising a proximal end and a distal end, wherein the distal end of the sleeve removably accommodates a needle; and (b) a wedge base for supporting the luminal needle sleeve, the wedge base comprising at least five (5) surfaces, wherein the wedge base supports the lumenal needle sleeve such that the needle sleeve is inclined at an angle in the range of 5° to 50°relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera.

In another aspect of the present invention, there is provided an apparatus for use in suprachoroidal delivery of a substance, said apparatus capable of resting over the surface of the eye for suprachoroidal delivery of at least a substance comprising: (a) a lumenal needle sleeve comprising a proximal end and a distal end, wherein the distal end of the sleeve removably accommodates a needle; and (b) a wedge base for supporting the luminal needle sleeve, the wedge base comprising at least five (5) surfaces, wherein the wedge base supports the lumenal needle sleeve such that the needle sleeve is inclined at an angle in the range of 5° to 50°relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera.

This summary is not intended to identify essential features of the claimed subject matter nor is it intended for use in determining or limiting the scope of the claimed subject matter.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

The following drawings form part of the present specification and are included to further illustrate aspects of the present disclosure. The disclosure may be better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein.

Fig. 1 depicts an apparatus for suprachoroidal delivery of at least a substance comprising a lumenal needle sleeve comprising a proximal end and a distal end, and a wedge base for supporting the luminal needle sleeve, in accordance with an embodiment of the present invention.

Fig. 2 depicts a needle sleeve accommodating a needle, in accordance with an embodiment of the present invention.

Fig. 3 depicts a needle entering the suprachoroidal space of eye via needle sleeve, in accordance with an embodiment of the present invention.

Fig. 4 depicts an apparatus for suprachoroidal delivery of at least a substance, further comprising a semilunar globe fixation ring, in accordance with an embodiment of the present invention. Fig. 5 depicts an apparatus for suprachoroidal delivery of at least a substance, further comprising a complete globe fixation ring, in accordance with an embodiment of the present invention.

Fig. 6 depicts an apparatus for suprachoroidal delivery of at least a substance, further comprising an extension globe fixating arm with corneal overbridge, in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Those skilled in the art will be aware that the invention described herein is subject to variations and modifications other than those specifically described. It is to be understood that the invention described herein includes all such variations and modifications. The invention also includes all such features referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more features.

Definitions

For convenience, before further description of the present invention, certain terms employed in the specification, examples are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. The terms used throughout this specification are defined as follows, unless otherwise limited in specific instances.

As used in the specification and the claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

The term "bevel" refers to the angled surface formed at needle point.

The term "length of bevel" refers to measurement from tip of needle to start of the bevel (heel) in a line parallel to the axis of the cannula.

The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only.

The present invention provides an apparatus capable of resting over the surface of the eye for suprachoroidal delivery of at least a substance comprising: (a) a lumenal needle sleeve comprising a proximal end and a distal end, wherein the distal end of the sleeve removably accommodates a needle; and (b) a wedge base for supporting the luminal needle sleeve, the wedge base comprising at least five (5) surfaces, wherein the wedge base supports the lumenal needle sleeve such that the needle is inclined at an angle in the range of 5° to 50°relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera.

In an embodiment, the apparatus of the present invention is made of metal, which can be autoclaved for multiple use. In a preferred embodiment, the metal used for manufacturing the apparatus can be surgical grade stainless steel. Surgical grade stainless steel can be 316, or 304 grade steel. Any other grade of stainless steel or metal or metal alloy may be used to manufacture the apparatus of the present invention. In another embodiment, the apparatus is made of non-autoclavable material and is disposable. The non-autoclavable material can be polymer-based. In yet another embodiment, at least a part of the apparatus is metal based and at least another part of the apparatus is polymer-based.

In an embodiment, the apparatus made of metal or polymer may be manufactured using molds. In another embodiment, the apparatus made of polymer can be 3D printed. Methods and technology of manufacturing which are known in the art may be employed to manufacture said apparatus. Said known manufacturing methods may be suitably modified to manufacture said apparatus.

In an embodiment, the angle of inclination of the needle relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera is an integral value between 5° and 50°. In another embodiment, the angle of inclination of the needle relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera is a fractional number between 5° and 50°. In a preferred embodiment, the angle of inclination of the needle relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera is an integer between 30 and 45. In a more preferred embodiment, the angle of inclination of the needle relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera is one of 30°, 35°, 40°, and 45°.

The angle of inclination of the needle or needle sleeve relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera is fixed in said apparatus. Most preferably, the fixed angle is one of 30°, 35°, 40° and 45°. It is also contemplated that the angle of inclination may be varied by way of adjustable sleeve, whereby the angle can be adjusted ±5° relative to angle of 30°, 35°, 40° or 45°.

The wedge base of the apparatus of the present invention essentially comprises a first and second surface opposite to each other; a third and fourth surface extending between the first and second surfaces, and intersecting at a common edge; and a fifth surface extending between the first, second, third, and fourth surface, wherein each edge of the fifth surface intersects with an edge of first, second, third, and fourth surface, and wherein at least a portion of the fifth surface forms a contoured profile substantially conforming to the curved profile of eye surface. In a preferred embodiment, the first and second surface are substantially flat. In a preferred embodiment, the third and fourth surface are substantially flat. The wedge base of the apparatus is essentially shaped like a 3D triangular prism.

The fifth surface of the wedge has an outer face At least a portion of the outer face has a concave contoured profile and substantially conforms to the curved convex profile of the eye or sclera surface. In a preferred embodiment, a substantial portion of the fifth surface substantially conforms to the contour of the eye. In a preferred embodiment, a substantial portion of the outer face of the fifth surface has a concave contoured profile and substantially conforms to the curved convex profile of the eye or sclera surface.

In the apparatus of the present invention, at least a portion of the fifth surface of the apparatus is ridged. At least a portion of the fifth surface has one or more ridges running across at least a portion of the length or width of the fifth surface. In an embodiment, there are multiple ridges running across at least a portion of the length of the fifth surface. In another embodiment, there are multiple ridges running across at least a portion of the width of the fifth surface. In a preferred embodiment, there are multiple ridges. In an embodiment, the ridges may be parallel to the length of the fifth surface. In an embodiment, the ridges may be parallel to the width of the fifth surface. In yet another embodiment, the ridges may be offset by an angle relative the length or width of the fifth surface. In an embodiment, the one or more ridges on the fifth surface runs across substantially the whole length or width of the fifth surface. In another embodiment, the one or more ridges on the fifth surface runs across a portion of the length or width of the fifth surface. In an embodiment, the one or more ridges are perpendicular to at least one edge of the fifth surface and extend towards the opposite edge. In an embodiment, one or more ridges are perpendicular to two opposite edges of the fifth surface and extend towards each other.

A ridge on the fifth surface of the wedge of the apparatus of the present invention consists of 2 walls intersecting at a common edge. In an embodiment, each wall of the ridge is of substantially the same length measured from base to common edge. In an embodiment, each wall of the ridge is of varying length measured from base to common edge. In an embodiment, the fifth surface has multiple ridges parallel to each other. In an embodiment, the multiple ridges are equidistant from each other. In another embodiment, the distance between two adjoining ridges may be variable. In an embodiment, the outer surface of the fifth surface may be substantially smooth.

In an embodiment, the apex of at least a ridge is curve shaped. In another embodiment, the apex of at least a ridge is flat shaped. In an embodiment, the apex of at least a ridge incorporates a flat and curved shape.

The at least one ridge on the fifth surface is for stabilizing the positioning and/or placement of the apparatus on the surface of the sclera.

The third surface of the wedge of the apparatus of the present invention is configured with a channel to receive and support the lumenal needle sleeve. The channel is parallel to the length (longitudinal axis) of the third surface. In an embodiment, the lumenal needle sleeve is an integral part of the third surface. In an embodiment, the sleeve may be located equidistant from opposite edges of the third surface. In another embodiment, the sleeve may be located off set towards one of the two opposite edges of the third surface.

The lumenal needle sleeve of the present invention comprises at least one window, wherein the window allows visualization of needle bevel orientation vis a vis scleral entry. In an embodiment, the sleeve has multiple windows. In a preferred embodiment, the sleeve comprises a single window located near the distal end of the sleeve. The window allows for needle bevel up or bevel down position vis a vis scleral entry.

The lumenal sleeve of the present invention accommodates 26-30-gauge hypodermic needle, and wherein the needle bevel length is in the range of 900-1300pm. The inner diameter of the sleeve is sufficiently larger than the outer diameter of the needle to allow smooth ingress and egress of the needle with minimal lateral movement of the needle within the sleeve. In an embodiment, the needle is 30-gauge needle.

The lumenal sleeve of the present invention is configured to allow the needle bevel tip to exit the distal end of the sleeve at a pre-defined angle and sufficiently to enter the suprachoroidal space under external pressure. The configuration allows for when a needle is inserted into the sleeve, the needle hub upon contact with the proximal end of needle sleeve prevents further ingress of the needle into the sleeve. The total length of the sleeve is such that when the needle hub contacts the proximal end of the sleeve, the needle bevel is completely exposed and outside the distal end of the sleeve. When the apparatus is positioned over the sclera, under external pressure, at least a part of the needle bevel, preferably the whole of the needle bevel is completely intrascleral when the needle hub is in contact with the proximal end of the sleeve.

The apparatus of the present invention further comprises at least a handle attached to any one or more of the surfaces of the wedge. In an embodiment, the apparatus comprises a handle attached to at least the first surface of the wedge. In an embodiment, the apparatus comprises a handle attached to at least the second surface of the wedge. The handle allows for positioning of the apparatus or wedge at desired location on the eye surface.

The apparatus of the present invention optionally further comprises a globe fixation device. The globe fixation device allows for immobilization of the eye so as to facilitate proper and stable positioning of the apparatus on eye surface. The globe fixation device also facilitates safe use of the apparatus and use thereof. In an embodiment, the globe fixation device can be a semilunar globe fixation ring. In an embodiment, the globe fixation device can be a complete globe fixation ring. In another embodiment, the globe fixation device can be an extension globe fixating arm with corneal overbridge. The surface of any of the globe fixation devices proximal to the eye surface may be ridged. The ridges may be as substantially described herein in this specification. In an embodiment, the surface of any of the globe fixation devices proximal to the eye surface may be substantially smooth.

The present invention also provides an apparatus as substantially described herein for use in suprachoroidal delivery of at least a substance. The substance may be a drug substance(s) for treatment of eye related pathology.

EXAMPLES

It is to be noted that the figures accompanying the present invention are merely to assist the reader and are representative in nature. The features of the figures are not to be construed literally as in any way limiting the scope of the detailed description of the invention. The figures are not necessarily to scale and certain features have been magnified for illustrative purposes. The figures only represent an embodiment of the invention. Variations and other embodiments, and combination of features of the apparatus of the present invention are equally contemplated and well within the expertise of a person skilled in the art to reasonably practice based on the description of the specification and figures accompanying the specification. As seen in Fig. 1, the apparatus 100 of the present invention comprises a lumenal needle sleeve 102; a wedge base 104 for supporting the lumenal needle sleeve. The wedge base comprises a first surface 104a, a second surface 104b, a third surface 104c a fourth surface 104d, and a fifth surface 104e; and a handle 108. The first surface 104a and the second surface 104b are opposite to each other, substantially flat, and parallel to each other. The third surface 104c is essentially flat and extends between the two edges of the first 104a and second 104b surface. The fourth surface 104d also extends between the two edges of the first 104a and second 104b surface. The third 104c and fourth 104d surface intersect at a common edge. The angle formed at the intersection is an acute angle. The fifth surface 104e has a contoured surface and extends between the first 104a, second 104b, third 104c, and fourth 104d surfaces. The fifth surface 104e is contoured to substantially conform to the shape of the eye when the apparatus is placed on eye surface. The fifth surface 104e has multiple ridges parallel to each other, each of which are equidistant from each other and run in a direction perpendicular to the length of the fifth surface 104e. The length of the ridges is less than half the width of the fifth surface 104e.

As seen in Fig. 2, the lumenal needle sleeve 202 comprises a proximal end 206, a distal end 204, and a window 210 located near the distal end 204 of the sleeve 202. The proximal end 206 is provisioned with a needle entry hub 208. A needle syringe 212 when fully inserted into the sleeve 202 has its bevel 214 region exposed outside the distal end 204 of the sleeve 202, while the needle hub 216 is in contact with the needle entry hub 208 to prevent further ingress of the needle into the sleeve 202. A minor part of the needle shaft may also be exposed to the outside from the distal end 204 of the sleeve when the needle bevel 214 is fully inside the sclera. Only for the purposes of ease of illustration, the needle thickness is shown to be substantially thinner than the lumenal width of the sleeve. However, it is understood that the outer diameter of the needle is comparable to the inner diameter of the lumen of the sleeve so as to allow entry and exit of the needle without significant lateral movement of the needle.

As seen in Fig. 3, in the configuration where the needle 304 is completely within the sleeve 302, the bevel 308 of the needle abuts from the distal end of the sleeve along with a portion of the needle shaft 306, and at least a portion of the needle shaft and the complete needle bevel in preferably bevel down position is intrascleral. The angle of entry of the needle into the sclera 310 is about 40°. As seen in Fig. 4, there is provided an apparatus 400 as substantially described herein with a semilunar globe fixation ring 402. The globe fixation ring assists in positioning of the apparatus 400 on the eye surface and also to immobilize the eye.

As seen in Fig. 5, there is provided an apparatus 500 as substantially described herein with a complete globe fixation ring 502. The globe fixation ring assists in positioning of the apparatus 500 on the eye surface and also to immobilize the eye.

As seen in Fig. 6, there is provided an apparatus 600 as substantially described herein with an extension globe fixating arm with corneal overbridge 602. The globe fixating arm assists in positioning of the apparatus 600 on the eye surface and also to immobilize the eye.

ADVANTAGES OF THE PRESENT INVENTION

The apparatus as described substantially in the present invention uses a commercially available 30-gauge hypodermic needle, obviating the need to use a microneedle. The apparatus of the present invention allows for the regular needle to enter the sclera obliquely at a designated angle as per scleral thickness and ensure suprachoroidal entry. The needle need not be altered or modified in any way for suprachoroidal entry. The apparatus ensures precise delivery into the suprachoroidal space and the oblique entry in addition ensures that there is no regurgitation. Further, this apparatus can be used in eyes that have not been anesthetized and only have surface sensory loss (topical anesthesia) temporarily during the use of the apparatus. Under normal circumstances, a normal commercially available hypodermic 30-gauge needle cannot be used for suprachoroidal drug delivery as they have a long bevel. If used and presented perpendicular to the sclera so that entire bevel is intrascleral, it would result in the needle entering inside the eye, into vitreous, or cause damage to the underlying retina and choroid. If used obliquely, without the apparatus, it will not be possible to deliver the drug consistently into the suprachoroidal space for lack of control of the angle of entry and the distance of needle travel intrasclerally. There will also be a great risk of causing damage to the retina or choroid and a greater chance of entering into the vitreous cavity.

Claims

We claim

1. An apparatus 100 capable of resting over the surface of the eye for suprachoroidal delivery of at least a substance comprising: a. a lumenal needle sleeve 102 comprising a proximal end and a distal end, wherein the distal end of the sleeve removably accommodates a needle; and b. a wedge base 104 for supporting the luminal needle sleeve, the wedge base comprising at least five (5) surfaces 104a, 104b, 104c, 104d, 104e, wherein the wedge base 104 supports the lumenal needle sleeve 102 such that the needle sleeve 102 is inclined at an angle in the range of 5° to 50° relative to a transverse plane across the surface of the sclera at a point of contact of needle with sclera.

2. The apparatus 100 as claimed in claim 1, wherein the angle is in the range of 30° to 45°.

3. The apparatus 100 as claimed in claim 1, wherein the wedge base 104 essentially comprises: a first 104a and second surface 104b opposite to each other; a third 104c and fourth surface 104d extending between the first and second surfaces, and intersecting at a common edge; and a fifth surface 104e extending between the first, second, third, and fourth surface, wherein each edge of the fifth surface intersects with an edge of first, second, third, and fourth surface, and wherein at least a portion of the fifth surface forms a contoured profile substantially conforming to the curved profile of eye surface.

4. The apparatus 100 as claimed in claim 3, wherein the third surface 104c is configured with a channel to receive and support said lumenal needle sleeve 102.

5. The apparatus 100 as claimed in claim 1, wherein the sleeve 102 further comprises at least one window 106, wherein the window allows visualization of needle bevel orientation vis a vis scleral entry.

6. The apparatus 100 as claimed in claim 1, wherein said lumenal needle sleeve accommodates 26-30-gauge hypodermic needle, and wherein the needle bevel length is in the range of 900-1300pm.

7. The apparatus 100 as claimed in claim 1, wherein the sleeve 102 is configured to allow the needle bevel tip to exit the distal end of the sleeve at a pre-defined angle and sufficiently enter the suprachoroidal space under external pressure.

8. The apparatus 100 as claimed in claim 1, further comprising at least one of handle 108, and optionally a globe fixation device, each connected to the wedge.

9. The apparatus as claimed in claim 8, wherein said globe fixation device is at least one of semilunar globe fixation ring 402, complete globe fixation ring 502, and an extension globe fixating arm with corneal overbridge 602.

10. The apparatus 100 as claimed in claim 3, wherein at least a portion of the fifth surface 104e is ridged.

11. The apparatus 100 as claimed in claim 10, wherein at least a portion of the fifth surface 104e has one or more ridges running across at least a portion of the length or width of the fifth surface 104e.

12. The apparatus 100 as claimed in claim 11, wherein the ridges may be spaced at regular or random intervals, wherein a ridge has 2 walls intersecting at a common edge, and wherein the walls of a ridge may be of substantially same or varying length measured from base to common edge.

13. The apparatus 100 as claimed in claim 8, wherein said lumenal needle sleeve 102, wedge base 104, handle 108, and optionally globe fixation device is a single integral unit.

14. The apparatus 100 as claimed in claim 1 for use in suprachoroidal delivery of at least a substance.