Claims:WE CLAIM:
1. A trabecular implant (100) comprising:
a curved hollow tube having a proximal end (101), the curved hollow tube defining a circumference, the curved hollow tube including a concave surface (100a);
characterized in that
a plurality of drainage holes (10) of a pre-defined length and width, the plurality of drainage holes (10) being disposed throughout the circumference of the curved hollow tube; and
a clamping structure 20 being disposed on the concave surface 100a of the curved hollow tube and at the proximal end 101, the clamping structure 20 including at least one vertical slit (20b, 20c and/or 20e) aligned along a curved longitudinal axis (‘a’) of the curved hollow tube and at least one horizontal slit (20a and/or 20d) aligned perpendicular to the at least one vertical slit (20b, 20c and/or 20e), wherein the horizontal slit (20a and/or 20d) and the vertical slit (20b, 20c and/or 20e) form a T-shaped structure.
2. The trabecular implant (100) as claimed in claim 1 wherein the curved hollow tube is bent at an angle ranging between 50°-90°.
3. The trabecular implant (100) as claimed in claim 1 wherein the plurality of drainage holes (10) includes 4-7 drainage holes (10).
4. The trabecular implant (100) as claimed in claim 1 wherein the pre-defined length and width ranges within 1.0 to 3.0 mm and 0.1 mm to 1.0 mm respectively.
5. The trabecular implant (100) as claimed in claim 1 wherein the clamping structure (20) includes one of an open configuration or a closed configuration.
6. The trabecular implant (100) as claimed in claim 5 wherein the open configuration includes one vertical slit (20b) and one horizontal slit (20a).
7. The trabecular implant (100) as claimed in claim 5 wherein the closed configuration includes two vertical slits (20c, 20e) and one horizontal slit (20d).
8. The trabecular implant (100) as claimed in claim 1 wherein the trabecular implant (100) is deployed with the help of a delivery system (200) having a gear mechanism (200b). , Description:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
TRABECULAR IMPLANT AND METHOD OF PREPARATION THEREOF

2. APPLICANT:
Meril Life Sciences Pvt. Ltd., an Indian company of the address Survey No. 135/139 Bilakhia House, Muktanand Marg, Chala, Vapi- 396191, Gujarat, India

The following specification particularly describes the invention and the manner in which it is to be performed:
FIELD OF INVENTION
[1] The present invention relates to a medical implant. More specifically, the present invention relates to a trabecular implant for treatment of primary open angle glaucoma (POAG).
BACKGROUND
[2] A human eye is a specialized sensory organ capable of light reception and is able to receive visual images. Aqueous humor is a transparent and watery fluid found in eye. Aqueous humor helps to maintains intraocular pressure inside the eye. In a healthy eye, aqueous humor is continually produced by ciliary processes and this rate of production is balanced by an equal rate of aqueous humor drainage.
[3] As new aqueous humor is secreted by the ciliary processes, a stream of aqueous humor flows out of an anterior chamber of the eye through a trabecular meshwork into schlemm's canal. This excess aqueous humor enters the venous blood stream (episcleral blood vessels) from schlemm's canal and is carried along with the venous blood leaving the eye. However, when the natural drainage mechanisms of the eye fail to function properly, the intraocular pressure inside the eye begins to rise. This rise in intraocular pressure causes damage to the optic nerve and results in loss of peripheral vision. As glaucoma progresses, more and more of the visual field is lost until the patient is completely blind.
[4] The most common type of glaucoma is ‘primary open angle glaucoma’ (POAG) is the most common form of glaucoma and is the leading cause of irreversible blindness around the world. POAG occurs gradually due to improper drainage of the aqueous humor fluid and a clogged drain in the eye of a patient.
[5] Most of the conventional treatment strategies for glaucoma are directed at lowering intraocular pressure through drops or pills. However, the eye drops and/or pills are proven to be temporarily effective for reducing the intraocular pressure and do not provide a promising solution.
[6] Recently, prosthetic implants have been used which may be implanted in the trabecular meshwork of the eye. However, such implants do not transfer the aqueous humor properly and have limited number of small drainage holes which further limit the drainage of aqueous humor.
[7] Further, the conventional implants do not get properly implanted at a treatment site. The conventional implants have increased susceptibility of migration from the treatment site post implantation.
[8] Also, these implants are mostly made of traditional titanium which restricts the flexibility and elasticity of the implant. Further, titanium implants have negligible biomechanical compatibility with adjoining tissues, resulting in loosening of the implants.
[9] Therefore, there exists a need for an improved implant which may overcome limitations of the conventional implants.
SUMMARY
[10] The present invention discloses a trabecular implant. The implant includes a curved hollow tube having a proximal end and a distal end. The curved hollow tube defines a circumference. The curved hollow tube includes a concave surface. The implant further includes a plurality of drainage holes of a pre-defined length and width. The plurality of drainage holes is disposed throughout the circumference of the curved hollow tube. The implant further includes a clamping structure being disposed on the concave surface of the curved hollow tube and at the proximal end. The clamping structure includes at least one vertical slit aligned along a curved longitudinal axis of the curved hollow tube and at least one horizontal slit aligned perpendicular to the curved longitudinal axis of the curved hollow tube. The horizontal slit and the vertical slit form a T-shaped structure.
[11] The above trabecular implant is deployed with the help of a delivery system. The delivery system of the present invention includes various components such as a delivery injector and a gear mechanism, a delivery handle, a supporting tube and a lock tube.
BRIEF DESCRIPTION OF DRAWINGS
[12] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.
[13] FIG.1 represents a trabecular implant deployed at the treatment site in accordance with an embodiment of the present invention.
[14] FIGs. 1a-1d depict different embodiments of the trabecular implant 100 in accordance with an embodiment of the present invention.
[15] FIGs. 2a-2b represent magnified views of different embodiments of clamping structure in accordance with an embodiment of the present invention.
[16] FIG. 3 depicts the delivery system 200 in accordance with an embodiment of the present invention.
[17] FIG. 4 represents a flow chart depicting a process involved in manufacturing the trabecular implant in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF DRAWINGS
[18] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.
[19] Particular embodiments of the present disclosure are described hereinbelow with reference to the accompanying drawings, however, it is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.
[20] The present invention relates to a trabecular implant. The trabecular implant is deployed at a treatment site i.e in schlemm’s canal of an eye to reduce intraocular eye pressure for prevention of glaucoma. In an embodiment, the trabecular implant is specifically used for the treatment of primary open angle glaucoma (POAG). The trabecular implant of the present invention facilitates smooth flow of aqueous humor fluid from anterior chamber of the eye to the schlemm's canal of the eye.
[21] The trabecular implant of the present invention includes a curved hollow tube having a plurality of wide drainage openings. The presence of wide drainage openings allows easy transfer of aqueous humor fluid from the anterior chamber to the schlemm's canal of the eye. Further, the trabecular implant includes a clamping structure at one or both ends. The trabecular implant includes a T-shaped clamping structure. The presence of T-shaped clamping structure provides improved holding of the trabecular implant with a delivery system thereby avoiding unwanted release of the trabecular implant prior to implantation at the treatment site.
[22] Now referring specifically to drawings, FIG. 1 depicts the trabecular implant 100 being implanted at the treatment site. As represented, the trabecular implant 100 may be implanted at the schlemm’s canal of the eye for drainage of the aqueous humor from the eye. In an embodiment, the trabecular implant 100 is utilized for treating glaucoma (POAG) by increasing the flow of aqueous humor to reduce intraocular pressure in the eye. The trabecular implant 100 creates an alternate passageway for the aqueous humor to escape from the eye, bypassing the eye’s damaged or clogged schlemm’s canal.
[23] FIGs. 1a-1d represent the trabecular implant 100. The trabecular implant 100 of the present invention may be made of any metallic material. The metallic material may include without limitation, stainless steel, cobalt-chromium, titanium, platinum, nitinol etc. In an embodiment, the trabecular implant 100 is made of nitinol. The utilization of nitinol is preferred in the present invention due to its enhanced shape memory property and excellent biocompatibility. Owing to enhanced shape memory of the nitinol, the trabecular implant 100 possesses greater flexibility and/or may be shaped as per anatomy of the treatment site.
[24] Alternatively, the trabecular implant 100 may be fabricated from a non-biodegradable biocompatible polymeric material. The polymeric material may include without limitation, polypropylene, polyethylene and polyurethane. Such polymers include properties such as high tensile strength and low compression ratio which make the trabecular implant 100 rigid enough to bear the flow of aqueous humor. Also, the polymeric trabecular implant 100 is flexible enough so that it can be easily implanted.
[25] The trabecular implant 100 includes a delivery configuration (as represented in FIG. 1a/1c) and a deployed configuration (as shown in FIG. 1b/1d). The delivery configuration corresponds to the configuration of the trabecular implant 100 at the time of its delivery. In an embodiment, for the ease of delivery, the trabecular implant 100 is linearly disposed (as represented in FIGs. 1a and 1c) over a delivery system (not shown).
[26] In deployed configuration, the trabecular implant 100 may be curved. In an embodiment, the trabecular implant 100 is manufactured as a curved hollow tube as shown in FIGs. 1b and 1c and attains the same structure post deployment. The trabecular implant 100 extends along a curved longitudinal axis ‘a’. In an embodiment as depicted in FIGs. 1b and 1c, the trabecular implant 100 is curved about the curved longitudinal axis ‘a’ so that a concave surface 100a is formed. The trabecular implant 100 may be bent at an angle in a range of 50° to 90° as per requirement of the patient.
[27] The trabecular implant 100 extends from a proximal end 101 to a distal end 103 of the trabecular implant 100. The distance between the proximal end 101 and the distal end 103 defines a length of the trabecular implant 100. The length of the trabecular implant 100 is such that trabecular implant 100 may have a greater angular span when implanted at the Schlemm’s canal of the eye. The length of the trabecular implant 100 may be in a range of 6mm to 12 mm, preferably in a range of 8mm to 10mm. In an embodiment, the length of the trabecular implant 100 is 10 mm. The length of trabecular implant 100 is more than the conventional implants which facilitates the flow of large amount of the aqueous humor from the anterior chamber of the eye.
[28] The trabecular implant 100 may include uniform or variable inner and outer diameters. In an embodiment, trabecular implant 100 includes a uniform inner and an outer diameter. The outer diameter of the trabecular implant 100 may be in a range of 0.5mm to 1.3mm and, preferably in a range of 0.8mm to 1.0mm. In an embodiment, the outer diameter of the trabecular implant 100 is 0.9 mm. The inner diameter of the trabecular implant 100 may be in a range of 0.50 mm to 0.60 mm and, preferably in a range of 0.53 mm to 0.56 mm. In an embodiment, the inner diameter of the trabecular implant 100 is 0.55 mm.
[29] The difference between the outer and inner diameters of the trabecular implant 100 may define the thickness of the trabecular implant 100. The thickness of the trabecular implant 100 may range between 0.16 mm to 0.19 mm. In an embodiment, the thickness of the trabecular implant 100 is 0.175 mm.
[30] As shown in FIGs. 1a-1d, the trabecular implant 100 may include a plurality of drainage openings 10. The drainage openings 10 may fluidly communicate with the schlemm’s canal of the eye. The drainage openings 10 may enable drainage of the aqueous humor fluid from the anterior chamber of the eye.
[31] The trabecular implant 100 may include 1-10, preferably 4-7 drainage openings 10. In an embodiment, the trabecular implant 100 includes 5 drainage openings 10. The number of drainage openings 10 in the trabecular implant 100 is more than the conventional implants which helps to efficiently maintain the flow of aqueous humor. The flow of the aqueous humor as maintained by the trabecular implant 100 may be in a range of 2µl/min to 4µl/min.
[32] The drainage openings 10 may be disposed in a pre-defined manner. In a preferred embodiment as shown in FIGs. 1a-1d, the drainage openings 10 are disposed throughout the length and circumference of the trabecular implant 100. Such disposition of the drainage openings 10 in the present invention promotes distribution of the aqueous humor throughout the trabecular implant 100 thereby eliminating the chances of concentration of pressure at a single site of the trabecular implant 100. Thus, the drainage openings 10 of the present invention prevent migration of the trabecular implant 100 and cause considerable reduction in intraocular pressure.
[33] Alternately, the drainage openings 10 may be disposed longitudinally in a straight line. Each of the drainage openings 10 may be disposed at a predefined distance from each other. The distance between each drainage opening 10 may be in a range of 1.5mm to 2.5mm, preferably 1.9mm to 2.2mm.
[34] Further, the amount of aqueous humor drained from the drainage openings 10 may depend upon the shape of the drainage openings 10. The shape of the drainage openings 10 may include any shape known in the art such as triangular, rectangle, rhombus, circle, square and elliptical etc. In an embodiment, the shape of the drainage opening 10 is elliptical. The elliptical shape of the drainage openings 10 may provide greater strength, more flexibility and/or greater capacity for the transfer of the aqueous humor from the anterior chamber of the eye to the schlemm’s canal.
[35] The size of the drainage openings 10 may also impact the amount of the aqueous humor drained from the eye. Larger size of the drainage openings 10 may tend to provide effective drainage of the aqueous humor. The length of the drainage openings 10 may be in the range of 1.0 to 3.0mm more preferably 1.8 mm to 2.5 mm. In an embodiment, the length of the drainage openings 10 is 2.24 mm. The width of the drainage openings 10 may range from 0.1 mm to 1.0 mm, more preferably 0.3 mm to 0.6 mm. In an embodiment, the width of the drainage openings 10 is 0.57 mm.
[36] The clamping structure 20 may be provided at least one of the proximal end 101 and/or the distal end 103 of the trabecular implant 100. In an embodiment, the clamping structure 20 is disposed over the concave surface 100a at the proximal end 101 of the trabecular implant 100 as depicted in FIGs. 1a-1d. The clamping structure 20 enables accurate attachment of the trabecular implant 100 with the delivery system.
[37] The clamping structure 20 may be an integral part of the trabecular implant 100 or may alternately form a separate structure being coupled to the trabecular implant 100. The clamping structure 20 may be provided in any shape as per a lock tube of the delivery injector such as a geometrical T shape, single curve cut, double curve cut, etc. In an embodiment, the clamping structure 20 is a T- shaped structure. The T- shaped structure of the clamping structure 20 ensures that the trabecular implant 100 may not get released from the delivery injector prior to reaching the treatment site. Further, the T shaped structure of the clamping structure 20 may provide support to the trabecular implant 100 and prevent migration of the trabecular implant 100 from the treatment site.
[38] The clamping structure 20 may be present in an open configuration (as depicted in FIG. 2a) or a closed configuration (as depicted in FIG. 2b). In open configuration, the proximal end 101 forms a top of the clamping structure 20 and hence, the clamping structure 20 extends from the proximal end 101 of the trabecular implant 100 till a pre-defined length towards the distal end 103 of the trabecular implant 100. Therefore, the clamping structure 20 is unlatched in open configuration and is exposed for attachment with a lock tube of the delivery system.
[39] The total length ‘A’ of the clamping structure 20 may lie within a range of 1.5mm to 3.00 mm. In an embodiment, the length ‘A’ of the clamping structure 20 is 2.75 mm.
[40] The clamping structure 20 in open configuration may include a horizontal slit 20a and a vertical slit 20b as shown in FIG. 2a. The vertical slit 20b may be disposed along the curved longitudinal axis ‘a’ while the horizontal slit 20a is aligned perpendicular to the curved longitudinal axis ‘a’ thereby forming a T-shaped structure.
[41] The horizontal slit 20a may include a predefined width ‘C’ and a length ‘E’. The width ‘C’ and the length ‘E’ may be in a range of 0.10mm to 0.30mm and 0.40mm to 0.90mm respectively. Likewise, the vertical slit 20b may include a predefined width ‘D’ and a length ‘B’. The width ‘D’ and the length ‘B’ may be in a range of 0.20mm to 0.40mm and 1.2mm to 2.8mm respectively. The clamping structure 20 facilitates attachment of the trabecular implant 100 with a lock tube of the delivery system (described below).
[42] In the open configuration, the clamping structure 20 causes smooth deployment of the trabecular implant 100. Further, the open configuration ensures faster delivery of the trabecular implant 100 at the treatment site.
[43] In closed configuration as represented in FIG. 2b, the clamping structure 20 includes a T-shaped component which extends from a first location near the proximal end 101 of the trabecular implant 100 till a pre-defined length towards the distal end 103 of the trabecular implant 100. The first location may be disposed around 0.1 mm to 1.0 mm below the proximal end 101 of the trabecular implant 100. In an embodiment, the first location is disposed around 0.15 mm below the proximal end 101 of the trabecular implant 100.
[44] The extension of the T-shaped component of the clamping structure 20 from the first location results in an improved fit of the trabecular implant 100 with the delivery system.
[45] As depicted in FIG.2b, the clamping structure 20 includes a first vertical slit 20c, a first horizontal slit 20d and a second vertical slit 20e. The first vertical slit 20c may extend from the proximal end 101 of the trabecular implant 100 till the first location along the curved longitudinal axis ‘a’. The length ‘F’ of the first vertical slit 20c may range between 0.1 mm to 1.0 mm. The distance ‘F’ may be in a range of 0.5mm to 1.0mm. In an embodiment, the length ‘F’ of the first vertical slit 20c is 0.15mm. The width ‘G’ of the first vertical slit 20c may range between 0.20 mm to 0.40 mm. In an embodiment, the width ‘G’ of the first vertical slit 20c is 0.26 mm.
[46] The first horizontal slit 20d and the second vertical slit 20e of the clamping structure 20 in closed configuration may be same or different from the horizontal slit 20a and the vertical slit 20b of the clamping structure 20 in open configuration respectively. In an embodiment, the first horizontal slit 20d and the second vertical slit 20e are same as the horizontal slit 20a and the vertical slit 20b respectively.
[47] The first horizontal slit 20d may include a predefined width ‘H’ and a length ‘I’. The width ‘H’ and the length ‘I’ may be in a range of 0.10mm to 0.30mm and 0.40mm to 0.90mm respectively. In an embodiment, the width ‘H’ and the length ‘I’ of the first horizontal slit 20d are from 0.10 mm to 0.30 mm and 0.40 mm to 0.90 mm respectively. In an embodiment, the width ‘H’ and length ‘I’ of the first horizontal slit 20d are 0.15 mm and 0.79 mm respectively.
[48] Likewise, the second vertical slit 20e may include a predefined width which is same as the width ‘G’ of the first vertical slit 20c and a length ‘J’. The length ‘J’ may be in a range of 1.2mm to 2.8mm. In an embodiment, the length ‘J’ of the second vertical slit 20e is 2.45 mm.
[49] The total length ‘K’ of the clamping structure 20 may lie within a range of 1.5 mm to 3.00 mm. In an embodiment, the length ‘K’ of the clamping structure 20 is 2.75 mm.
[50] In closed configuration, the gradual formation of T-shaped component from the proximal end 101 results in excellent fit of the trabecular implant 100 with the delivery system. The first vertical slit 20c provides additional support during attachment with the delivery system thereby enhancing the efficiency to prevent the dislodgement of the trabecular implant 100 prior to reaching the treatment site.
[51] The above disclosed trabecular implant 100 is deployed at the treatment site using a delivery system 200 as depicted in FIG. 3. The delivery system 200 of the trabecular implant 100 may include one or more of, a delivery injector 200a and a gear mechanism 200b, a delivery handle 200c, a supporting tube 200d and a lock tube 200e.
[52] The delivery injector 200a may be disposed at a distal end of the delivery system 200. The delivery injector 200a is a curved tube which facilitates the access of the delivery system 200 into the Schlemm’s canal. The design of the delivery injector 200a may be as per the anatomy of the treatment site. The delivery injector 200a may be curved at an angle of 40° to 100° more preferably 60° to 80° for ease of implantation.
[53] The gear mechanism 200b of the delivery system 200 is a mechanical mechanism utilized for deployment of the trabecular implant 100 at the treatment site. The gear mechanism 200b may include at least two gears which form a gear train. In an embodiment, the gear mechanism 200b includes a spur gear, idler gear and a rack gear, which are in association with each other to constitute a gear train. The said gears have pre-defined number of teeth.
[54] The spur gear acts as a driver. In an embodiment, the spur gear is connected with idler gear for its motion. The idler gear is disposed between the spur gear and the rack gear. The idler gear serves to transmit the rotation from the spur gear to rack gear. The rack gear of the gear mechanism 200b is indirectly driven by the spur gear. In an embodiment, the rack gear is meshed with the idler gear. The rack gear may be in contact with the lock tube 200e and hence, causes the linear movement of the lock tube 200e.
[55] Hence, the gear mechanism 200b of the delivery system 200 operates to translate rotational motion into linear motion of the lock tube 200e for deployment of the trabecular implant 100. The gearing mechanism 200b is very smooth and has high accuracy between meshed teeth of the spur gear and the rack gear.
[56] The trabecular implant 100 is deployed at the treatment site by using the delivery handle 200c. The delivery handle 200c includes a length which ranges between 200mm to 280mm and more preferably 220mm to 260mm. In an embodiment, the length of the delivery handle 200c is 220mm to 260mm. The delivery handle 200c may be made of a pre-defined material such as acrylonitrile butadiene styrene (ABS), polycarbonates, polyamides etc. In an embodiment, the delivery handle 200c is made of acrylonitrile butadiene styrene (ABS).
[57] The delivery handle 200c may house the components of the gear mechanism 200b within itself, along with the lock tube 200e, the supporting tube 200d, etc. The delivery handle 200c may include a structure that can be easily held and operated by a user. The trabecular implant 100 is attached with the delivery handle 200c through the lock tube 200e. The operation of delivery handle 200c includes conversion of rotational motion of the spur and idler gears into linear motion of the rack gear via rotation of a wheel. The linear motion of the rack gear helps to advance the lock tube 200e at the treatment site.
[58] The supporting tube 200d of the delivery system 200 is a hollow tube which is disposed inside the rack gear. The supporting tube 200d may be fixed to the rack gear. The supporting tube 200d functions to support the lock tube 200e.
[59] The supporting tube 200d may be made up of any rigid metallic material known in the art. In an embodiment, the supporting tube 200d is made of stainless steel.
[60] The lock tube 200e of the delivery system 200 functions to hold the trabecular implant 100 and temporarily attached with the clamping structure 20 of the trabecular implant 100 at the time of delivery. The said attachment the lock tube 200e and the clamping structure 20 ensures that the trabecular implant 100 is firmly held in the delivery injector 200a during delivery thereby preventing any possibility of dislodgement of the trabecular implant 100 from the delivery system 200 prior to its implantation.
[61] The lock tube 200e can be manufactured using a shape memory alloy such as nitinol (NiTi), stainless steel (SS), cobalt chromium (CoCr), etc. In an embodiment, the lock tube 200e is made of stainless steel.
[62] The lock tube 200e may include a first end e1 and a second end e2. The first end e1 may attach to the clamping structure 20 of the trabecular implant 100 while the second end e2 is connected with the rack gear. The first end e1 may include a lock structure e3 which includes a shape which is dependent upon the shape of the clamping structure 20 of the trabecular implant 100. The lock structure e3 ensures that during implantation, the trabecular implant 100 is easily deployed at the treatment site without getting stuck into the delivery injector 200a.
[63] The deployment of trabecular implant 100 is performed with the help of the above disclosed delivery system 200. In an embodiment, deployment is performed through the rotation of the wheel present on the delivery handle 200c. In an embodiment, the wheel is rotated in a clockwise direction which results in the movement of the spur gear. The rotation motion of spur gear in turn advances the rack gear. The movement of rack gear further results in motion of the lock tube 200e inside the delivery injector 200a. The trabecular implant 100 attached at a distal end of lock tube 200e also advances further. Gradually the wheel is rotated until the trabecular implant 100 projects out of the delivery system 200 and is detached from the lock tube 200e.
[64] FIG. 4 represents a method for fabrication of the trabecular implant 100. Eventhough the trabecular implant 100 of the present invention may be made from a metal or a polymer, the below method discloses the steps to be performed for fabrication of trabecular implant 100 using a nitinol tube.
[65] The process of manufacturing of the trabecular implant 100 commences at step 401. At this step, the nitinol tube having a predefined diameter and thickness is cut to form a cut tube having drainage openings 10 and the clamping structure 20. The diameter and the thickness of the nitinol tube may directly influence the strength of the trabecular implant 100. The diameter of the nitinol tube may be in a range of 0.75mm to 1.25mm, preferably 0.85mm to 0.95mm. The thickness of the nitinol tube may be in a range of 100µ to 250µ, preferably 150µ to 200µ.
[66] The cutting of the nitinol tube may be performed by any conventionally known means such as, without limitation, liquid jet machining, laser cutting, abrasive jet machining, etc. In an embodiment, the cutting is performed by means of laser cutting. Various experimental factors which may affect the process of laser cutting may include laser power, pulse width etc. The process of laser cutting maybe performed with the help of argon gas at a pressure of 6bar to 15bar, preferably 9bar to 12bar. The pulse width maintained during the laser-cutting process may range between 0.005ms and 0.020ms, preferably 0.010ms and 0.015ms. Further, the laser power may lie in a range of 50W to 110W, preferably 70W to 90W.
[67] Further, at step 403, the cut tube obtained at the previous step is subjected to a process of grinding and honing to achieve a finished tube having a smooth surface. Post laser cutting, the cut tube may include burrs and welds. Grinding of the cut tube is performed in order to remove welds and burrs. Grinding and honing are used to make smooth surface finishes inside bores or to hold precise tolerances of bore diameter of the cut tube.
[68] In an embodiment, grinding and honing are consecutively performed. After grinding, the remaining burrs of the cut tube may be removed by the honing process.
[69] The process of grinding and honing may be performed by means of an abrasive stone which acts as a filer. In an embodiment, the abrasive stone used in the present invention is a diamond filer. In present invention diamond file D-91, D-64, D-54 are used for grinding purpose and D-30 for honing process. The process of grinding may be performed until the burrs are removed from the cut tube.
[70] The process of honing may be performed by means of an abrasive stone. The process may include inserting a mandrel inside the trabecular implant 100 to remove debris from the internal surface of the trabecular implant 100. A lubricant may also be used for easy removal of the debris.
[71] In an embodiment, fluids and/or powders like glycol or a homogeneous blend of sodium linear alkylaryl sulfonate, alcohol sulfate, phosphates, carbonates (powder) may be used to provide smooth cutting action and to remove cut material from a bore. Further, a lubricant may be used for easy removal of debris from the finished tube. Post grinding and honing, the finished tube may be cleaned with purified water.
[72] At step 405, the finished tube is subjected to a process of shape setting to form the trabecular implant 100. Shape setting results in the formation of the trabecular implant 100 which is sufficiently flexible to assume a shape matching the curvature of the schlemm’s canal post its implantation.
[73] The shape setting may be performed by means of heat treatment of the finished tube using a mold. The mold may be in the form of a curved mandrel having a predefined radius of curvature. The radius of curvature of the mold may be in a range of 40° to 100°, preferably 50° - 90°. In an embodiment, the radius of curvature of the mold is 90°. The mold may include a predefined thickness in a range of 0.2mm to 0.8mm, preferably 0.4mm to 0.6mm. The mold may be made of any conventional metal such as without limitation, stainless steel, nitinol, cobalt-chromium etc. In an embodiment, the mold is made of the stainless steel. The mold of the present invention may provide a desired flexibility to the finished tube to form the trabecular implant 100.
[74] The process of heat treatment of the trabecular implant 100 may be performed in a fluidized bath reactor. The heat treatment may be performed at a temperature in a range of 480°C - 540°C, preferably 500°C - 520°C for a time duration of 3 minutes to 20 minutes, preferably 5 minutes to 15 minutes.
[75] In an embodiment, a powder of aluminum oxide is sprinkled on the finished tube for effective heat treatment during shape setting. The process of heat treatment and subsequent cooling generates stress in molecular structure of the nitinol which may provide permanent required shape to the material.
[76] After completion of shape setting, the trabecular implant 100 is removed from the fluidized bath and immediately immersed into water. The said step produces a martensite transformation of the trabecular implant 100. This consecutive heating and cooling step imparts reversible transformation of nitinol from an austenite form to martensite thereby rendering shape memory properties to the trabecular implant 100.
[77] At step 407, the trabecular implant 100 is subjected to a process of sand blasting. The process of sand blasting may be performed by means of aluminum oxide powder. The aluminum oxide powder is allowed to strike on an outer surface of the trabecular implant 100 at a predefined frequency for a predefined period of time. The predefined frequency and the predefined time may be in a range of 45 to 85 Hz and 3minutes to 10 minutes. In an embodiment, the frequency is in range of 55 to 65 Hz and time is 5minutes to 8minutes. The pressure exerted by the powder may vary in a range of 20 psi to 90 psi, preferably in a range of 30 psi to 60 psi. The process sand blasting may produce highly smooth outer surface of the trabecular implant 100 due to abrasion with the aluminum powder. The process of sand blasting may also remove oxide layers, striations left by laser cutting in previous step, decrease propensity for micro cracking and/or provide light texture to the outer surface of the trabecular implant 100.
[78] At step 409, the trabecular implant 100 is subjected to a process of electro-polishing. After sand blasting at step 407, an oxide layer is formed on the surface of the trabecular implant 100. Further, the trabecular implant 100 may include sharp edges, micro burrs, welds and other impurities. Hence, for removal of micro burrs, welds and sharp edges electro-polishing process is performed.
[79] The process of electropolishing is performed by immersing the trabecular implant 100 in a solution of electrolytes. The electrolytes to be used in the present invention mostly include acids havng high viscosity. The electrolytes may be concentrated acid solution such as mixture of perchlorates with acetic anhydride and methanolic solutions of sulfuric acid.
[80] In a beaker, electrolytes are added and copper plates are attached as cathode and the trabecular implant 100 to be polished is attached as anode. An appropriate voltage and current is charged in the circuit with help of external source like battery, power supply, etc. for a predefined time duration. The voltage used for the electro polishing is from 5V to 12V, preferably from 7V to 10V and the current is from 0.6A to 1.2A and preferably 0.7A to 1A. The process of electropolishing may be performed one or more cycles. The number of cycles may range from 1 to 5 and more preferably 2 to 4. The predefined time duration for each cycle may be in a range of 1 to 5 minutes, preferably 2 to 4 minutes. In an embodiment, the said process is performed in three cycles of 1.5 minute each at the voltage of 9V and current 0.9A.
[81] Optionally/ additionally, the trabecular implant 100 obtained at the previous step is coated with therapeutic agent. The therapeutic agent may help in reducing inflammatory reaction after the trabecular implant 100 is implanted at the treatment site. Further, the therapeutic agents may also help in reducing the intra-ocular pressure by decreasing the production of the aqueous humor and/or by increasing drainage of the aqueous humor.
[82] The drug may be coated by any method such as spray coating, dip coating, spin coating etc. In an embodiment, the drug is coated by means of the spray coating.
[83] The therapeutic agent may be selected from any class of drugs namely anti-proliferative agents, anti-hypertensive agents like beta blockers, alpha agonists, carbonic anhydrase inhibitors, Rho kinase inhibitor,s etc. The anti-proliferative agents may include sirolimus, everolimus, tacrolimus, zotarolimus, paclitaxel and the like. The beta blocking agents may include timolol, atenolol, acebutolola and the like. The alpha agonists may include agents like brimonidine, midodribe, methoxamine and the like. The carbonic anhydrase inhibitors may include dorzolamide, brinzolamide, acetazolamide, methazolamide etc. The Rho kinase inhibitors may include fasudil, ripasudil, netarsudil and the like.
[84] In an embodiment, a formulation of the therapeutic agent may be prepared with a polymer. The polymer may control the release of drug from the trabecular implant 100. The polymer may include without limitation poly-DL-lactide co-glycolide, poly-L-lactide, poly-L-lactide co-glycolide, polycaprolactone, poly-DL-lactide or a mixture thereof. Further in the embodiment, the drug polymer solution can be formulated in organic solvents like dichloromethane, acetone, chloroform or methanol or a mixture of solvents.
[85] The invention will now be explained with the help of following examples.
Example 1 (Prior art)
[86] A trabecular implant ‘A’ having a cylindrical and curved structure was evaluated for its patency and positioning at the treatment site. The implant ‘A’ included three drainage holes aligned along a longitudinal axis in a single line. The dimensions of the drainage holes included a length of 0.85 mm and a width of 0.32 mm. The implant ‘A’ included an arc-like shaped clamping structure (curved configuration) for attachment with the delivery system.
[87] The delivery system loaded with the implant ‘A’ was evaluated for deploying the implant in a pre-defined location under simulated condition. After deploying the implant ‘A’, it was observed that the implant could not be released properly from the delivery system and hence was deployed 03-04 mm distally from the pre-defined location. The implant ‘A’ was found to have a tendency of dislodging from the delivery system prior to reaching the treatment site.
[88] Further, the implant ‘A’ was studied in an in-vitro model where the implant was deployed in a mock vessel having a PBS fluid flow similar to the flow of aqueous humor in the eye i.e., 2.5µl/min. It was observed that the implant ‘A’ migrated at the treatment site when observed after one hour of the study. Further, the implant ‘A’ was found to migrate more than 30-40% from its original deployed position.
Example 2 (Present invention)
[89] A trabecular implant ‘B’ having a cylindrical and curved structure was evaluated for its patency and positioning at a treatment site. The implant ‘B’ included five wide drainage holes throughout the circumference having a length and a width of 2.24 mm and 0.57 mm respectively. The implant ‘B’ included a T- shaped clamping structure (as described above) for attachment with the delivery system.
[90] The delivery system loaded with the implant ‘B’ was tested under simulated use conditions. Post deployment, it was observed that the implant ‘B’ was deployed precisely at the treatment site.
[91] The implant ‘B’ was studied in an in-vitro model where the implant ‘B’ was deployed in a mock vessel having a PBS fluid flow similar to the flow of aqueous humor in the eye i.e., 2.5µl/min. The disposition of drainage holes throughout the circumference of the implant ‘B’ allowed fluid distribution leading to maximum drainage of aqueous humor. The fluid distribution ensured that a specific area of the implant ‘B’ was not subjected to stress of the fluid flow thereby eliminating the chances of migration of the implant ‘B’ from the treatment site. It was observed that unlike the implant ‘B’ of the previous example, the implant ‘B’ of the present example, migrated considerably less and was well apposed at the treatment site when observed after one hour of the study. The implant ‘B’ did not dislodge from the delivery system prior to reaching the treatment site. Further, the implant ‘B’ was found to migrate less than 10% from its original deployed position. Hence, the implant ‘B’ of the present example ensured accurate conformability at the treatment site and smooth as well as accurate deployment at the treatment site.
[92] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.