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:
LASER-CUT TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT IMPLANT

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

3. The following specification particularly describes the invention and the manner in which it is to be performed:

The following complete specification is filed as a patent of addition application of the Indian patent application no. 202021007600, filed on 22nd February, 2020.

FIELD OF INVENTION
[001] The present invention relates to a medical implant, more specifically, a transjugular intrahepatic portosystemic shunt implant.
BACKGROUND OF INVENTION
[002] The liver serves many functions within the body from making carbohydrates, proteins and fats to synthesizing bile for digestion of food. In order to perform the said functions, the liver requires a significant blood supply and around 75% of this blood supply comes from the portal venous system.
[003] Portal hypertension is an increase in the blood pressure within the portal venous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver. In cases where the vessels in the liver are blocked due to liver damage, blood is not able to flow properly through the liver and hence, high pressure in the portal system is developed. This increased pressure in the portal vein may in turn cause development of large, swollen veins within the esophagus, stomach, rectum, or umbilical area (belly button), thereby leading to life-threatening complications.
[004] In order to treat portal hypertension, transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) was introduced in the year 1969. TIPS is an artificial channel which is provided within the liver to establish a communication between the portal vein and the hepatic vein. TIPS have proven to be a promising procedure for safe decompression of the portal system and effective control of blood pressure flow.
[005] Ever since the advent of this procedure, various systems have been proposed. In recent practice, varied stent platforms have been used as artificial channels. Most of the stents are either laser cut or knitted/braided. However, the conventional stents pose various challenges. For example, the said stents mostly require a pull wire or a thread for their deployment. Such deployment mechanisms may cause improper deployment of the stent as the pull wire or the thread is susceptible to breakage/damage due to unstable forces. Further, the conventional stents are prone to kinking at puncture site (junctions) because of their placement at bending segments of the liver anatomy. Also, most of the conventional stents have poor bending flexibility and often contact or protrude the hepatic and portal veins post deployment to cause complications like clotting/thrombosis and blockage of the shunt.
[006] Further, most of the conventional stents are associated with enhanced chances of migration of the stent from a target site thereby compromising on the efficiency of the stent owing to uniform diameter across their length.
[007] Therefore, an improved system for TIPS which overcomes the disadvantages of the conventional systems is required to be devised.
SUMMARY OF INVENTION
[008] The present invention relates to a laser-cut transjugular intrahepatic portosystemic shunt implant. The implant includes a proximal end section and a distal end section. Each of the proximal end section and the distal end section includes at least one row of closed end cells that are formed by connecting two adjacent rows of struts. A middle section is flanked by the proximal end section and the distal end section. The middle section is covered by a covering thereby conferring enhanced radial strength to the middle section. The middle section includes a plurality of rows of cells formed by interconnecting two adjacent rows of struts. The plurality of rows of cells includes a first row of closed cells, a second row of closed cells and a plurality of intermediate rows of cells disposed between the first row of closed cells and the second row of closed cells.
[009] The first row of closed cells proximate to the proximal end section while the second row of closed cells is proximate to the distal end section. Each row of the plurality of intermediate rows of cells includes open and closed cells that alternate with each other.
[0010] In an undeployed state, the proximal end section and the distal end section are flared at an angle of 90 degrees with respect to a longitudinal axis ‘L’ of the implant. The proximal end section and the distal end section are configured to adjust basis an implantation site and flare at a pre-defined angle with respect to the longitudinal axis ‘L’ of the implant in deployed state.
[0011] The closed end cells of the proximal end section and the distal end section are dimensioned to be larger than the closed cells of the middle section and devoid of the covering thereby, imparting flexibility to the proximal end section and the distal end section and preventing kinking of the implant.
BRIEF DESCRIPTION OF DRAWINGS
[0012] 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.
[0013] FIG. 1 depicts an implant 100 being deployed at an implantation site in accordance with an embodiment of the present invention.
[0014] FIG. 2 depicts the exploded view of the implant 100 in accordance with an embodiment of the present invention.
[0015] FIGs. 3a-3b represents a first frame 10a in accordance with an embodiment of the present invention.
[0016] FIGs. 3c-3e represents a second frame 10b in accordance with an embodiment of the present invention.
[0017] FIG. 4 a mandrel 20 in accordance with an embodiment of the present invention.
[0018] FIGs. 5-5b depicts the attachment between the first frame 10a and the second frame 10b in accordance with an embodiment of the present invention.
[0019] FIG. 6 depicts an implant 200 deployed at the implantation site in accordance with an embodiment of the present invention.
[0020] FIG. 6a shows the structure of the implant 200 in accordance with an embodiment of the present invention.
[0021] FIG. 6b depicts an exploded view of a flared proximal end section 200a1 of the implant 200 in accordance with an embodiment of the present invention.
[0022] FIG. 6c depicts a side upper view of the implant 200 illustrating the flared ends in accordance with an embodiment of the present invention.
[0023] FIG. 7 depicts an implant ‘Z’ of prior art in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE ACCOMPANYING DRAWINGS
[0024] 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.
[0025] Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment, but mean “one or more but not all embodiments” unless expressly specified otherwise. The terms “including,” “comprising,” “having,” and variations thereof mean “including but not limited to” unless expressly specified otherwise. An enumerated listing of items does not imply that any or all of the items are mutually exclusive and/or mutually inclusive, unless expressly specified otherwise. The terms “a,” “an,” and “the” also refer to “one or more” unless expressly specified otherwise.
[0026] Although the operations of exemplary embodiments of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that the disclosed embodiments can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular embodiment are not limited to that embodiment, and may be applied to any embodiment disclosed herein. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses.
[0027] Furthermore, the described features, advantages, and characteristics of the embodiments may be combined in any suitable manner. One skilled in the relevant art will recognize that the embodiments may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments. These features and advantages of the embodiments will become more fully apparent from the following description and appended claims, or may be learned by the practice of embodiments as set forth hereinafter.
[0028] In accordance with the present disclosure, a medical implant to be employed as a transjugular intrahepatic portosystemic shunt is disclosed. The implant is useful for treatment of liver diseases such as portal hypertension, gastrointestinal bleeding, hepatic encephalopathy (HE), refractory ascites, etc. The implant of the present invention helps to establish a shunt through a portal vein and a hepatic vein for diverting the blood flow at an implantation site. The implantation site in the present invention corresponds to the intrahepatic tract of the liver. The implant helps to divert and increase the blood flow from the liver thereby reducing blood pressure in the portal vein as well as reducing any associated risk of bleeding of the dilated veins.
[0029] The implant of the present invention is a self-expanding implant. The implant includes a laser-cut single frame structure having a middle section flanked by a flared proximal end section and a flared distal end section (or flared end sections).
[0030] Once deployed, the implant extends from a first junction between the portal vein and the intrahepatic tract to a second junction between the hepatic vein and the intrahepatic tract. Hence, the implant of the present invention is deployed in such a manner that the none of the ends of the implant contact/protrude into with the hepatic and the portal vein. Such a deployed position of the implant eliminates any chances of blood clot formation or thrombosis post deployment that are generally associated with conventional implants.
[0031] The flared end sections help to fix the implant at the first and the second junctions by maintaining proper grip and hold at the implantation site while diverting blood flow thereby reducing chances of migration of the implant from the implantation site. Also, owing to the flared end sections of the present invention, issues relating to kinking as witnessed in the conventional implant due to improper placement and positioning of the implants are addressed by the present invention.
[0032] Further, the middle section of the implant includes a plurality of rows of cells. Each row includes a pattern of alternating open and closed cells.
[0033] The middle section of the implant includes a covering on its outer surface. The covering corresponds to a polymer covering having self-reinforcing properties, high radial resistance and resistance to damage caused by bile and other fluids is provided over the implant. The polymeric covering further allows passage of the blood through the portal vein to the hepatic vein without any leakage through the implant surface.
[0034] The implant includes a plurality of markers disposed at different locations for ensuring accurate placement of the implant between the portal vein and the hepatic vein.
[0035] The implant of the present invention is deployed via a 7Fr to 10Fr compatible delivery system. The delivery system operates via a push-pull mechanism. The said delivery system allows easy and accurate placement of the implant in the intrahepatic tract.
[0036] Now referring to figures, FIG.1 depicts an embodiment of a transjugular intrahepatic portosystemic shunt implant of the present invention, hereon referred as ‘implant 100’. The implant 100 is disposed at the implantation site i.e. intrahepatic tract 1a of the liver 1. The placement of the implant 100 is carried out via an endoluminal pathway through a jugular vein (not shown) which links a portal vein 1b disposed towards an inferior vena cava 1c to a hepatic vein 1d. As depicted in FIG. 1, the implant 100 is placed between the hepatic vein 1d and the portal vein 1b. The structure of the implant 100 is more clearly depicted in FIG. 2.
[0037] In accordance with FIG. 2 of the present invention, the implant 100 may include a body defined between a proximal end 100a and a distal end 100b. The proximal and distal ends 100a, 100b may be flared. The flared proximal and distal ends 100a, 100b prevent migration of the implant 100 thereby allowing the implant 100 to be held firmly at the implantation site. The difference between the diameter of the proximal and distal ends and the diameter of the rest of the body of the implant 100 may range from 0.1mm to 3.0mm, more preferably from 0.5mm to 1.5mm.
[0038] Further, the implant 100 includes a plurality of sections which are linked together to form the implant 100. Such sections may include distinct properties such as, without limitation, flexibility, softness and radial strength. The implant 100 may be a single frame structure (discussed in detail below) or may include a plurality of frames. In an embodiment of the present invention as depicted in FIG. 2, the implant 100 includes a first frame 10a and a second frame 10b. In an embodiment, the first frame 10a is highly flexible. Such flexibility of the first frame 10a helps the implant 100 to be held firmly inside the vein and further assists in forming a grip for the transfer of blood. The second frame 10b may be less flexible and may include a higher radial strength and kink resistive properties. Such properties help the implant 100 to be deployed at implantation sites having high bending curves (as per a patient’s anatomy).
[0039] The first frame 10a is placed towards the proximal end 100a or the distal end 100b of the implant 100. In an embodiment as depicted in FIG. 2, the first frame 10a is disposed at the distal end 100b. The first frame 10a may include a first proximal end 10a1 and a first distal end 10a2. The first proximal end 10a1 may be attached to the second frame 10b while the first distal end 10a2 may correspond to the distal end 100b of the implant 100.
[0040] The total length of the first frame 10a may be in a range 10mm to 40mm; more preferably 15mm to 35mm. The diameter of the first frame 10a may be in a range of 4mm to 14mm, more preferably 8mm to 12mm.
[0041] The first frame 10a may be made up of conventionally known metals such as, without limitation, cobalt chromium, stainless steel, nitinol, nitinol platinum core wire, platinum or platinum tungsten material, etc. In an embodiment of the present invention, the first frame 10a is made of nitinol. Nitinol is used for preparation of the first frame 10a because of its pronounced self-expanding properties as compared to other materials.
[0042] As a preferred embodiment, the first frame 10a is made via braiding of nitinol wires. However, as per the teachings of the said invention, the first frame 10a may be manufactured by other techniques such as laser cutting, knitting or braiding, etc. The first frame 10a includes a plurality of closed cells. The size of the said closed cells may be increased for a given diameter of the first frame 10a to obtain a first frame 10a having a less metal ratio and high flexibility. The increase in the size of the closed cells in turn reduction in the number of wires to be used for braiding. In an embodiment, around 8 to 32 wires, preferably, 12 to 24 wires are braided together to create the first frame 10a.
[0043] In an embodiment, the wires used for preparing the first frame 10a may be monofilament or multifilament. The wire diameter may be in a range of 50micron to 300micron, more preferably 100micron to 200micron.
[0044] The braiding configuration adopted for preparation of the first frame 10a may be one of, one by one, one by two, two by two, etc. In an embodiment, one by one braiding configuration is adopted for manufacturing the first frame 10a. The braid angle may be in a range of 30° to 500°; more preferably 100° to 400°.
[0045] As represented in FIGs. 2 and 3a, the first frame 10a is braided in such a way that at least one of the first proximal end 10a1 and/or the first distal end 10a2 of the first frame 10a includes long updown loops 10a3. Such a structure may be formed using a mandrel 20 (as shown in FIG. 4).
[0046] In an embodiment, the length of the updown loops 10a3 range from 2mm to 6mm, more preferably 3mm to 4mm. The number of updown loops 10a3 may vary between 1 to 4 loops. The updown loops 10a3 help to maintain the flexibility of the implant 100 at a point where the first proximal end 10a1 is coupled to the second frame 10b.
[0047] Alternately, as represented in FIG. 3b, the first frame 10a includes a closed loop structure at both its sides without any updown loops 10a3.
[0048] Further, the first frame 10a may further include a plurality of markers. The markers may be placed at the first proximal end 10a1 and the first distal end 10a2. In an embodiment, 2 to 10 markers are placed for radiopacity, more preferably 4 to 8 markers are used. The radiopaque markers may be designed in the form of a tube, coil, sheet or any other design. In an embodiment, the first frame 10a includes tube shaped markers which help to maintain flexibility and profile of the implant 100.
[0049] The radiopaque markers are made from a biocompatible material such as platinum, iridium, platinum tungsten, tantalum, gold or their combination. In an embodiment, markers made from platinum tungsten material are used in the present invention. The markers may include an internal diameter of 50-300 micron and a wall thickness of 2-5 micron.
[0050] The second frame 10b may include a second proximal end 10b1, a second distal end 10b2 and an intermediate portion 10b3. The second proximal end 10b1 is disposed towards the proximal end 100a of the implant 100 as depicted in FIG. 2. The second distal end 10b2 may be coupled to the first proximal end 10a1 of the first frame 10a.
[0051] The second frame 10b may be made from conventionally known material such as nitinol, platinum-iridium alloys, stainless steel, cobalt chromium alloys including elgiloy. In an embodiment, the second frame 10b is made of nitinol shape memory alloy.
[0052] In an embodiment, the second frame 10b is formed via laser cutting. However, as per the teachings of the present invention, the second frame 10b may be fabricated using conventional techniques such as laser-cutting, braiding/knitting, etc.
[0053] As represented in FIG. 3c, the second frame 10b may include a plurality of rows of closed cells (CC) as well as open cells (OC). In an embodiment, the second proximal end 10b1 and the second distal end 10b2 include closed cells (CC) while the intermediate portion 10b3 includes open cells (OC) to improve the flexibility of the second frame 10b. Further, such a design also promotes easy loading of the implant 100.
[0054] The total number of cells may range from 8-16 radially, more preferably 10-14. However, it should be noted that the number of cells may also increase with increase in the diameter of the second frame 10b. The diameter of the second frame 10b may range from 4mm to 14mm, more preferably 8mm to 12mm. The second frame 10b may include a total length in a range of 20mm to 200mm, more preferably 60mm to 120mm.
[0055] The closed cells ‘CC’ of the second frame 10b may be attached with the open cells ‘OC’ with the help of plurality of links ‘L’ as shown in FIG. 3c. Further, as represented in FIG. 3c, in closed cells ‘CC’, a pair of zig-zag struts is connected together via the link ‘L’ to form a hexagonal shaped crown. The zig-zag shaped struts may correspond to peaks of the closed cell ‘CC’. The links of the closed cell may be designed as a straight structure or a curve. In a preferred embodiment, the links are straight in configuration.
[0056] The width of the link ‘L’ of the closed cells ‘CC’ may be same as the width of the struts. In an embodiment, the width of the link is range from 0.08mm to 0.18mm, more preferably 0.10 mm to 0.14mm. The length of a strut in the closed cell ‘CC’ may range from 2.0mm to 3.0mm, more preferably 2.2mm to 2.6mm. The strut thickness may range from 0.10mm to 0.20mm, more preferably 0.12 mm to 0.18mm.
[0057] The length cell offset (CO) as shown in the FIG. 3d for a closed cell may be in a range of 3.0mm to 6.0mm, more preferably 3.5mm to 5.0mm. The mean cell spacing (MCS) of the closed cells ‘CC’ may be less as compared to the MCS of the open cell. In an embodiment, the MCS of the closed cells ‘CC’ ranges from 2.0mm to 3.0mm, more preferably 2.2mm to 2.6mm. The length of the peak ‘P’ as shown in FIG. 3d may range from 0.2mm to 0.3mm; more preferably 0.22mm to 0.26mm. The strut angle ‘a’ i.e. the angle formed after the expansion of the implant 100, may range from 90° to 130°; more preferably 100° to 120°.
[0058] The open cell structure ‘OC’ may include 04 to 30 peaks, more preferably 06 to 20 peaks that are circumferentially disposed. The struts in the open cells ‘OC’ are also interconnected via links ‘L’. However, the link ‘L’ in the open cells are less than the number of links ‘L’ in the closed cells ‘CC’. The links ‘L’ is arranged in such a manner that the strength of the second frame 10b is maintained as well as the flexibility and bending property of the second frame 10b is enhanced.
[0059] The width of the links may be same as the strut width of the cells. The width of the links may be in a range from 0.08mm to 0.18mm, more preferably 0.10mm to 0.14mm.
[0060] The length of the struts in the open cells ‘OC’ may be in a range of 1mm to 3mm; more preferably 2.2mm to 2.6mm. The strut thickness of the open cells ‘OC’ may be in a range of 0.10mm to 0.20mm; more preferably 0.12 mm to 0.18mm. The length of the peak ‘P’ as shown in FIG. 3e may be in a range of 0.2mm to 0.3mm; more preferably 0.22mm to 0.26mm. The length of the open cell ring cell offset ‘CO’ may be in a range of 3.0mm to 6.0mm; more preferably 3.5mm to 5.0mm. The mean cell spacing ‘MCS’ of the open ring cell may be in a range of 2.0mm to 3.0mm; more preferably 2.2mm to 2.6mm. The strut angle ‘a’ (angled formed after the expansion of the implant 100) of the open cell ring may be in a range of 90° to 130°; more preferably 100° to 120°.
[0061] In an embodiment, the first frame 10a and the second frame 10b may be secured with each other as shown in FIG. 5. The first frame 10a and the second frame 10b may be joined by way of interweaving. Each braided thread of the first frame 10a may be interwoven with the close cells ‘CC’ of the second frame 10b at the second distal end 10b2. As represented in FIG. 5b, in case of updown loops 10a3, the loops having longer length are attached at the second distal end 10b2 of the second frame 10b. Such a combination helps to maintain the placement of the first frame 10a to hold the portal vein 1b and the second frame 10b to act as a bridge between the portal vein 1b and hepatic vein 1d. In an embodiment, the first frame 10a covers around 10% to 30% of the length of the total implant 100.
[0062] In another embodiment as depicted in FIG. 5a, the updown loop 10a3 of the first frame 10a overlap with the closed cells ‘CC’ of the second frame 10b at specific points which are at least distance from the second distal end 10b2. Such a combination allows easy bending of the implant 100 due to high flexibility. Also, better fixation and reduced chance of leakage are achieved.
[0063] In an embodiment of the present invention, one or more markers are attached at one of the second proximal end/the second distal end 10b1, 10b2 of the second frame 10b for better visibility of the implant 100. In present embodiment, 02 to 06 markers are attached on the one side for the visibility of the second frame 10b under fluoroscopy; more preferably 03 to 04 markers are attached on the one side of the second frame 10b. These markers are may be round or tube shaped which are press fit or laser welded.
[0064] Further, a covering is provided over the second frame 10b. The said covering may be provided by many ways like adhesion, spray coating, electrospining, etc. Such covering includes self-reinforcing properties, high radial resistance and resistance to damage caused by bile and other fluids. The covering further allows passage of the blood through the portal vein 1b to the hepatic vein 1d without any leakage through the implant surface.
[0065] In an embodiment, the covering is a polymeric covering being composed of one or more degradable or non-degradable polymers. The non-degradable polymers may include, without limitation, polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), silicone, fluorinated ethylene propylene (FEP), etc. The degradable polymers may be selected from say, polylactic acid (PLLA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), etc. In an embodiment, expanded polytetrafluoroethylene (ePTFE) is used. This ePTFE may include an unsintered membrane with a preferred thickness ranging from 0.003 mm to 0.10 mm, more preferably thickness ranges from 0.005 mm to 0.09 mm. Such low thickness of ePTFE helps to maintain the low profile of the implant 100. The dimensions and the number of ePTFE films required to cover the second frame 10b is dependent upon the inner or outer diameter of frame and the thickness of the film along with the number of wraps required.
[0066] Thus, depending on the thickness of the film and inner and outer diameters of the second frame 10b, the numbers of wraps or films are calculated. In an embodiment, two films were minimally required to provide an appropriately thick ePTFE covering/film with a 0.5mm thick film placed over the entire length of the second frame 10b.
[0067] The ePTFE layer may be covered on the implant surface via for example, heating, coating, gluing etc. In preferred embodiment, an ePTFE layer is covered on an inner or an outer surface of the implant 100 by applying heat which secures the polymer onto the implant 100. The said covering may be easily expanded without reducing the flexibility of the implant 100.
[0068] In an embodiment, in order to provide the ePTFE covering over the implant 100, the mandrel 20 is used (as shown in FIG.4). The mandrel 20 provides smooth covering of ePTFE without any crack and wrinkles. The said mandrel 20 may be made from a polymeric or a metal material like teflon, HDPE, stainless steel, nitinol etc. In this present invention, the mandrel 20 is made of stainless steel material. The mandrel 20 contains one or more holes 20a to circulate air. Also, a central hole 20a1 is provided over the mandrel 20 which provides uniform heat exchange throughout the surface of the mandrel 20. The mandrel 20 also includes a slit 20b which helps to remove the covered implant 100. In an embodiment, the central hole 20a1 includes a diameter of 2.5 mm, the one or more air hole 20a include a diameter of 1.95mm and the slit 20b includes a diameter of 1mm–2mm.
[0069] For providing the covering over the second frame 10b, the mandrel 20 mounted with the implant 100 having the ePTFE layer was heated at a temperature of about 150°C to 600°C for 05min to 30 min; more preferably 180°C to 220°C for 10min to 25 min respectively. To shrink the ePTFE layer properly, a heat shrink tube was laid over the ePTFE layer for protecting the outer surface which is directly in contact to heat. The dimensions of the heat shrink tube may be more than the implant dimensions, particularly the diameter. The heat shrink tubes used in the present invention may include fluorinated ethylene propylene, PTFE, nylon, pebax etc. In an embodiment, fluorinated ethylene propylene is used. Subsequently, the mandrel 20 having the implant 100 is cooled at the normal temperate to gain the strength of graft bonding. The mandrel 20 may be cooled for say, 1 min to 15 mins; more preferably 5mins to 10 mins. Post cooling, the heat shrink tube is removed.
[0070] The first and second frames 10a, 10b as described above, may be attached together using a coupling mechanism or some pre-defined methodologies.
[0071] FIG. 6 depicts another embodiment of the transjugular intrahepatic portosystemic shunt implant of the present invention, hereon referred as implant 200. Like the implant 100, the implant 200 is placed in the intrahepatic tract 1a extending between the hepatic vein 1d and the portal vein 1b for maintaining proper flow of the blood through the vessels. As evident from FIG. 6, the implant 200 extends from a first junction ‘j1’ between the portal vein 1b and the intrahepatic tract 1a to a second junction ‘j2’ between the hepatic vein 1d and the intrahepatic tract 1a. Hence, the implant 200 is deployed in such a manner that the implant 200 does not protrude into with the hepatic and the portal veins 1d, 1b. Such a deployed position of the implant 200 eliminates any chances of blood clot formation or thrombosis post deployment that are generally associated with conventional implants.
[0072] An exploded view of the implant 200 is shown in FIG. 6a. The implant 200 may be made of a material similar to the second frame 10b of the implant 100. Hence, the examples of materials and preferred embodiments have not been reiterated for the sake of brevity.
[0073] In an embodiment, the implant 200 is a laser-cut transjugular intrahepatic portosystemic shunt implant. For example, the implant 200 is formed by laser-cutting a nitinol tube in a specified pattern. The dimensions of the tube used may define the dimensions of the implant 200. The implant 200 may include a diameter ranging from 6 to 16 mm and a total length ranging from 60 to 200 mm.
[0074] Instead of two frames as included in the implant 100, the implant 200 is a single frame self-expandable structure that extends from a proximal end 200a to a distal end 200b along a longitudinal axis ‘L’ as shown in FIG. 6a.
[0075] The implant 200 includes a middle section 200c flanked by a proximal end section 200a1 and a distal end section 200b1. In an embodiment, the proximal end section 200a1 and a distal end section 200b1 are disposed at the proximal and distal ends 200a, 200b respectively. The proximal end section 200a1 and the distal end section 200b1 are more flexible as compared to the middle section 200c (described in detail below).
[0076] As seen from FIG. 6a, the proximal and distal end sections 200a1, 200b1 are flared. The proximal and distal end sections 200a1, 200b1 may be flared with respect to the longitudinal axis ‘L’ at an angle ‘x’ ranging between 30 to 180 degrees. In an embodiment, the implant 200 is constructed in a manner that the proximal and distal end sections 200a1, 200b1 are initially flared at an angle of 90 degrees with respect to the longitudinal axis ‘L’ in its undeployed state. However, at the time of deployment, due to the flexibility of the proximal end section 200a1 and the distal end section 200b1, the proximal end section 200a1 and the distal end section 200b1 flex and adjust to conform to anatomical flaring at the implantation site, particularly the first and the second junction ‘j1’,’j2’ and flare accordingly at the angle ‘x’ ranging between 30 to 180 degrees in deployed state, as shown in FIG. 6.
[0077] Such flaring helps to fix the implant 200 at the portal vein 1b and the hepatic vein 1d such that proper grip and hold at the implantation site is maintained while diverting blood flow thereby reducing chances of migration of the implant 200 from the implantation site. Also, given the flared proximal and distal end sections 200a1, 200b1 seat at the first and second junctions ‘j1’, ‘j2’ without protruding into the hepatic or portal veins 1d, 1b, there is no kinking observed in the implant 200.
[0078] As shown in FIG. 6a, the implant 200 includes a plurality of rows of zig-zag shaped struts that are circumferentially oriented. The rows of zig-zag shaped struts are interconnected with each other to define a plurality of rows of cells like the second frame 10b.
[0079] Each of the proximal end section 200a1 and the distal end section 200b1 include at least one row of closed end cells 201c formed by connecting two adjacent rows of struts (described below in detail). In an embodiment, each of the proximal end section 200a1 and the distal end section 200b1 includes a proximal end row of zig-zag struts 201a and a distal end row of zig-zag struts 201b respectively. Given the proximal end section 200a1 and the distal end section 200b1 are flared, the proximal end row of the zig-zag struts 201a and the distal end row of zig-zag struts 201b also flare outwardly as better illustrated in FIG. 6c.
[0080] Each of the struts included in the proximal end row of zig-zag struts 201a and the distal end row of zig-zag struts 201b may have a pre-defined shape. An exploded view of the proximal end and distal end rows of zig-zag struts 201a, 201b is shown in FIG. 6b.
[0081] The length ‘A’ of each strut may range between 5 to 15mm. Each strut may include a width and thickness of 100 to 300 micron. Instead of being straight, each strut may be slightly curved. Owing to the curved shape of the struts, each strut may include a substantially straight section D and a bump section E. The length of the substantially straight section D and the bump section E may range between 1-5 mm. Such a shape of the struts helps to easily crimp the implant 200 to a specified diameter complimentary to a delivery system.
[0082] As evident from FIG. 6b, each strut of the proximal end row of zig-zag struts 201a and the distal end row of zig-zag struts 201b, connects with adjacently placed struts to form peaks ‘p’ and valleys ‘v’. The interconnection of the struts to form the peaks ‘p’ and valleys ‘v’ may be smooth and curved.
[0083] The peaks ‘p’ and the valleys ‘v’ may include an outer radius ‘B’ and an inner radius ‘C’ ranging between 0.2 to 1.0mm.
[0084] The peaks ‘p’ may be directed towards the proximal end 200a while the valleys ‘v’ may be directed towards the distal end 200b of the implant 200. Hence, the peaks ‘p’ of the proximal end row of zig-zag struts 201a are free and define the proximal end 200a of the implant 200. While, the valleys ‘v’ of the distal end row of zig-zag struts 201b are free and define the distal end 200b of the implant 200.
[0085] The valleys ‘v’ of the proximal end row of zig-zag struts 201a and the peaks ‘p’ of the distal end row of zig-zag struts 201b are connected to the middle section 200c via a plurality of first links 200d1. Such interconnection helps to define at least one row of closed end cells 201c in the proximal end section 200a1 and the distal end section 200b1 (as shown in FIG. 6a and more clearly illustrated in FIG. 6b).
[0086] The first links 200d1 may include a pre-defined shape such as S-shape, straight, zig-zag shaped, etc. In an embodiment as shown in FIG. 6a, the first links 200d1 are straight. The first links 200d1 may include a length of 0.2 to 0.8mm and a width of 100 to 200 micron.
[0087] In an embodiment, the plurality of closed end cells 201c are in the form of leaf-shaped closed cells as shown in FIG. 6a. The incorporation of such a shape and structure of closed cells in the present invention confers flexibility to the proximal and distal end sections 200a1, 200b1 and also enhances the surface area of the proximal and distal end sections 200a1, 200b1 thereby allowing better grip of the implant 200 at the implantation site. Hence, owing to the aforesaid, the implant 200 can be securely held at the implantation site without any migration risks.
[0088] The number of closed end cells 201c at each of the proximal end section 200a1 and the distal end section 200b1 may vary depending upon the diameter of the implant 200. Alternately, irrespective of the diameter of the implant 200, the number of closed end cells 201c may be same, with variation only in the dimensions of the closed end cells 201c. In an embodiment, the implant 200 includes four closed end cells 201c at each of the proximal end section 200a1 and the distal end section 200b1.
[0089] The middle section 200c may include a plurality of rows of cells formed by interconnection of two adjacent rows of struts. More particularly, the plurality of rows of cells are formed by interconnecting a plurality of rows of intermediate zig-zag struts. Each strut of the plurality of rows of intermediate zig-zag struts may be a slightly curved strut and connects with adjacently placed struts of a row to form peaks ‘p1’ and valleys ‘v1’. The interconnection of the struts to form the peaks ‘p1’ and valleys ‘v1’ may be smooth and curved. The peaks ‘p1’ may be directed towards the proximal end 200a while the valleys ‘v1’ may be directed towards the distal end 200b of the implant 200.
[0090] In an embodiment, the peaks ‘p1’ of the row of intermediate zig-zag struts that is disposed adjacent to the proximal end row of zig-zag struts 201a (hereon referred as ‘proximal end row of intermediate zig-zag struts 200c1) is selectively connected to the valleys ‘v’ of the proximal end row of zig-zag struts 201a via the first links 200d1. Likewise, the valleys ‘v’ of the row of intermediate zig-zag struts that is disposed adjacent to the distal end row of zig-zag struts 201b (hereon referred as ‘distal end row of intermediate zig-zag struts 200c2) is selectively connected to the peaks ‘p’ of the distal end row of zig-zag struts 201b via the second links 200d2. Such interconnections may lead to the formation of the closed end cells 201c as elaborated above.
[0091] The number of peaks ‘p1’ and valleys ‘v1’ in the proximal and distal end row of intermediate zig-zag struts 200c1, 200c2 struts may be more than the number of peaks ‘p’ and valleys ‘v’ in the proximal and distal end rows of zig-zag struts 201a, 201b. Owing to such a difference, each valley ‘v’ of the proximal end row of zig-zag struts 201a connects with every third peak ‘p1’ of the proximal end row of intermediate zig-zag struts 200c1. Likewise, each peak ‘p’ of the distal end row of zig-zag struts 201b connects with every third valley ‘v1’ of the distal end row of intermediate zig-zag struts 200c2. It should be noted that third peak/valley connection is only exemplary in nature and can be varied depending upon the number of peaks ‘p1’/’p’ and valleys ‘v1’/’v’ included in the proximal and distal end rows of intermediate zig-zag struts 200c1, 200c2 and the proximal and distal end rows of zig-zag struts 201a, 201b respectively.
[0092] The valleys ‘v1’ of the proximal end row of intermediate zig-zag struts 200c1 are connected to the peaks 'p1' of an adjacently placed row of intermediate zig-zag struts (hereon referred as ‘middle row of intermediate zig-zag struts) to form a first row of closed cells 200c3. Hence, the first row of closed cells 200c3 are placed proximate to the proximal end section 200a1. Likewise, the peaks ‘p1’ of the distal end row of intermediate zig-zag struts 200c2 are connected to the valleys 'v1' of an adjacently placed middle row of intermediate zig-zag struts to form a second row of closed cells 200c3. Hence, the second row of closed cells 200c3 are placed proximate to the distal end section 200b1. Such interconnections may be facilitated by a plurality of second links 200d2.
[0093] The second links 200d2 may include a pre-defined shape such as S-shape, straight, zig-zag shaped, etc. In an embodiment as shown in FIG. 6a, the second links 200d2 are straight. The second links 200d2 may include a total length of 0.2 to 0.8mm and a width ranging between 100-500micron. The second links 200d2 positioned near the proximal and distal end sections 200a1, 200b1 act as transition elements between the middle section 200c and the flared end sections 200a1, 200b1 thereby preventing any deformation of the implant 200.
[0094] The total number of closed cells in each of the first and second rows of closed cells 200c3 may vary depending upon the diameter of the implant 200, the number of peak ‘p1’ and valleys ’v1’. In an embodiment, the number of closed cells in each of the first and second rows of closed cells 200c3 are same.
[0095] The closed cells may include a pre-defined shape. In an embodiment as shown in FIGs. 6a and 6b, the closed cells have hexagonal shape. It should be noted that the closed end cells 201c are dimensioned larger than the closed cells of the middle section 200c thereby imparting flexibility to the proximal end section 200a1 and the distal end section 200b1 and preventing kinking of the implant 200.
[0096] In an embodiment, each middle row of intermediate zig-zag struts is connected with an adjacently placed middle row of intermediate zig-zag struts as shown in FIG. 6a. The plurality of intermediate rows of cells 200c4 is disposed between the first row of closed cells 200c3 and the second row of closed cells 200c3. Each of the plurality of intermediate rows of cells 200c4 include open and closed cells that alternate with each other.
[0097] The third links 200d3 may include a pre-defined shape such as S-shape, straight, zig-zag shaped, etc. In an embodiment as shown in FIG. 6a, the second links 200d2 are straight. The third links 200d3 may include a total length of 0.2 to 0.8mm and a width ranging between 100-500micron.
[0098] Such connection is made via connecting peaks ‘p1’ of one middle row of intermediate zig-zag struts with the valleys ‘v1’ of an adjacently placed middle row of intermediate zig-zag struts. In order to form open and closed cells that alternate with each other, the peaks ‘p1’ and valleys ‘v1’ are connected in a predefined manner. As an exemplary embodiment, table 1 is provided below:
S. No. A first middle row of intermediate zig-zag struts An adjacently placed middle row of intermediate zig-zag struts Row of cells
1 Valley 1 Connected to corresponding peak 1 Closed cell 1
2 Valley 2 Connected to corresponding peak 2
3 Valley 3 Not connected to corresponding valley 3 Open cell 1
4 Valley 4 Connected to corresponding peak 4 Closed cell 2
5 Valley 5 Connected to corresponding peak 5
6 Valley 6 Connected to corresponding peak 6 Open cell 2
7 Valley 7 Connected to corresponding peak 7
Table 1
Though table 1 mentions interconnection of valley 1-7 with peaks 1-7, the same may be repeated depending upon the number of peaks ‘p1’ and valleys ‘v1’ in the middle row of intermediate zig-zag struts. The rows of cells formed in accordance with the connection illustrated in Table 1 is also shown in FIG. 6a.
[0099] The total number of open and closed cells may vary depending upon the length and diameter of the implant 200. In an embodiment, in present invention number of open and close cells around 5-20 depending upon the length and diameter of the implant 200.
[00100] Each intermediate row of cells 200c4 includes alternating closed cells and open may or may not include equal number of closed and open cells. In an embodiment, the number of closed and open cells are same in each intermediate rows of cells 200c4.
[00101] Owing to the above-described structure of the implant 200, the implant 200 exhibits excellent radial strength against compressive forces at the implantation site, thereby making the implant 200 prolapse resistant. In other words, the implant 200 can easily resist and endure the compressive forces at the implantation site post deployment thereby providing increased torque-ability, flexibility and kink resistance.
[00102] Like the implant 100, the implant 200 may also be covered by a polymeric covering. The polymeric covering may be same as the polymeric covering disclosed above and hence, the details have not been re-iterated for the sake of brevity. The implant 200 is covered in such a way that the proximal and distal end sections 200a1, 200b1 are free while the polymeric covering completely covers the middle section 200c. Hence, the closed end cells 201c remain uncovered thereby imparting flexibility to the proximal end section 200a1 and the distal end section 200b1 and preventing kinking of the implant 200. The covered middle section confers enhanced radial strength to the middle section 200c.
[00103] Further, the implant 200 may be provided with a plurality of markers like the implant 100. The material and construction of markers in the implant 200 may be same as the implant 100 and hence, have not been re-iterated for the sake of brevity.
[00104] In an embodiment, each of the proximal and distal end sections 200a1, 200b1 may be provided with four markers. In an embodiment, each marker is in the form of a strip having a thickness of 15-30micron, a length of 0.8-1.2mm and a width of 0.1-0.5mm. In an embodiment, the markers are provided over the first links 200d1.
[00105] The foregoing invention has been explained by way of the following examples:
[00106] Example 1(Prior art): A metallic implant ‘Z’ made up of nitinol with uniform diameter was employed to be used as a transjugular intrahepatic portosystemic shunt. The said implant ‘Z’ was placed in the intrahepatic tract for the proper flow of the blood through the vessels. As shown in FIG. 7, the implant ‘Z’ included a laser cut construction having a uniform diameter throughout its length. The implant ‘Z’ included two sections, a first section and a second section. The first section included a combination of open cells and closed cells, and was covered with a PTFE covering. The second section included a plurality of dumbbell shape cells without any covering.
[00107] The implant ‘Z’ was placed between the hepatic and the portal vein. The first section of the implant ‘Z’ covered an area from the portal vein to the hepatic vein. The second section was placed in the hepatic vein to divert the blood flow in the first section and transfer directly into the portal vein.
[00108] It was observed that the second section of the implant kinked at the junction point (i.e. where the puncture is done to place shunt) leading to blockage of the shunt as shown in FIG. 7.
[00109] Also, it was found that the implant ‘Z’ migrated from the implantation site due to improper deployment at the target location and high blood pressure at portal vein.
[00110] Example 2 (Present Invention): The implant 200 of the present invention was implanted in the intrahepatic tract without any contact with the hepatic or portal veins. Only the middle section 200c of the implant 200 was covered with an ePTFE cover. The implant 200 included flared proximal and distal end sections 200a1, 200b1 without any cover. The implant 200 was delivered using a delivery system equipped with push-pull mechanism and was compatible with 7Fr and/or 10Fr compatibility.
[00111] It was observed that the implant 200 was easily deployed in the intrahepatic tract without any special precaution (under in-vitro simulation model). Also, the flared and flexible proximal, distal end sections 200a1, 200b1 provided firm grip of the implant 200 at the first and second junctions ‘j1’, ‘j2’. No kinking or migration of the implant 200 from the implantation site was observed. Further, the enhanced radial strength of the middle section 200c of the implant 200 provided a rigid shunting structure to maintain excess blood flow from the portal vein towards the hepatic vein.
[00113] 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. , Claims:WE CLAIM
1. A laser-cut transjugular intrahepatic portosystemic shunt implant (200) comprising:
a proximal end section (200a1) and a distal end section (200b1), each of the proximal end section (200a1) and the distal end section (200b1) includes at least one row of closed end cells (201c) formed by connecting two adjacent rows of struts; and
a middle section (200c) flanked by the proximal end section (200a1) and the distal end section (200b1), the middle section (200c) having a plurality of rows of cells formed by interconnecting two adjacent rows of struts, the plurality of rows of cells including:
a first row of closed cells (200c3) proximate to the proximal end section (200a1);
a second row of closed cells (200c3) proximate to the distal end section (200b1); and
a plurality of intermediate rows of cells (200c4) disposed between the first row of closed cells (200c3) and the second row of closed cells (200c3), wherein each row of the plurality of intermediate rows of cells (200c4) includes open and closed cells that alternate with each other,
wherein in an undeployed state, the proximal end section (200a1) and the distal end section (200b1) are flared at an angle of 90 degrees with respect to a longitudinal axis ‘L’ of an implant (200),
wherein the proximal end section (200a1) and the distal end section (200b1) are configured to adjust basis an implantation site and flare at a pre-defined angle ‘x’ with respect to the longitudinal axis ‘L’ of the implant (200),
wherein the middle section (200c) is covered by a covering thereby conferring enhanced radial strength to the middle section (200c), and
wherein the closed end cells (201c) being dimensioned to be larger than the closed cells of the middle section (200c) and devoid of the covering thereby, imparting flexibility to the proximal end section (200a1) and the distal end section (200b1) and preventing kinking of the implant (200).
2. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, the at least one row of closed end cells (201c) includes leaf-shaped closed cells.
3. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, the pre-defined angle ranges from 30-180 degrees.
4. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, the covering includes a polymeric covering.
5. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, the at least one row of closed end cells (201c) of the proximal end section (200a1) includes:
a proximal end row of zig-zag struts (201a), the proximal end row of zig-zag struts (201a) includes a plurality of alternating peaks ‘p’ and valleys ‘v’;
a proximal end row of intermediate zig-zag struts (200c1), the proximal end row of intermediate zig-zag struts (200c1) includes a plurality of alternating peaks ‘p1’ and valleys ‘v1’; and
a plurality of first links (200d1) connecting the valleys ‘v’ of the proximal end row of zig-zag struts (201a) to the peaks ‘p1’ of the proximal end row of intermediate zig-zag struts (200c1).
6. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, the at least one row of closed end cells (201c) of the distal end section (200b1) includes:
a distal end row of zig-zag struts (201b), the distal end row of zig-zag struts (201b) includes a plurality of alternating peaks ‘p’ and valleys ‘v’;
a distal end row of intermediate zig-zag struts (200c2), the distal end row of intermediate zig-zag struts (200c2) includes a plurality of alternating peaks ‘p1’ and valleys ‘v1’; and
a plurality of first links (200d1) connecting the peaks ‘p’ of the distal end row of zig-zag struts (201b) to the valleys ‘v1’ of the distal end row of intermediate zig-zag struts (200c2).
7. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claims 1 and 6 wherein, the first row of closed cells (200c3) includes the valleys ‘v1’ of the proximal end row of intermediate zig-zag struts (200c1) connected to the peaks 'p1' of an adjacently placed middle row of intermediate zig-zag struts via a plurality of second links (200d2).
8. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claims 1 and 6 wherein, the second row of closed cells (200c3) includes the peaks ‘p1’ of the distal end row of intermediate zig-zag struts 200c2 connected to the valleys 'v1' of an adjacently placed middle row of intermediate zig-zag struts via a plurality of second links (200d2).
9. The laser-cut transjugular intrahepatic portosystemic shunt implant (200) as claimed in claim 1 wherein, each of the plurality of intermediate rows of cells (200c4) includes a middle row of intermediate zig-zag struts selectively connected with an adjacently placed middle row of intermediate zig-zag struts via a plurality of third links (200d3).