Source: http://patents.com/us-9987027.html
Timestamp: 2018-11-14 21:36:13
Document Index: 121685708

Matched Legal Cases: ['art\n5836032', 'art\n6350271', 'Application No. 13735641', 'Application No. 201380005571', 'Application No. 13735641', 'Application No. 201380005571', 'Application No. 2013208660', 'Application No. 201380005571', 'Application No. 2014', 'Application No. 13735641', 'Application No. 2014', 'Application No. 2014', 'Application No. 2014', 'Application No. 2014', 'Application No. 61', 'art 14']

US Patent # 9,987,027. Device and method for removing occlusions in a biological vessel - Patents.com
United States Patent 9,987,027
Ben-Ami June 5, 2018
Ben-Ami; Doron Jacob (Ramat-HaSharon, IL)
Triticum Ltd. (Ramat-HaSharon, IL)
Family ID: 1000003327455
14/315,352
US 20140309657 A1 Oct 16, 2014
PCT/IL2013/050049 Jan 15, 2013
61586792 Jan 15, 2012
Current CPC Class: A61B 17/22031 (20130101); A61B 2017/22094 (20130101); A61B 2017/22034 (20130101)
4765332 August 1988 Fischell
5003657 April 1991 Boiteau
5009659 April 1991 Hamlin
5133733 July 1992 Rasmussen
5192290 March 1993 Hilal
5370653 December 1994 Cragg
5522825 June 1996 Kropf et al.
5769960 June 1998 Nirmel
5827304 October 1998 Hart
5836032 November 1998 Hondo
5895400 April 1999 Abela
5984965 November 1999 Knapp
6027514 February 2000 Stine
6254571 July 2001 Hart
6350271 February 2002 Kurz
6692504 February 2004 Kurz et al.
6775873 August 2004 Luoma
7008434 March 2006 Kurz et al.
D610761 February 2010 Gengler
7731731 June 2010 Abela
8021379 September 2011 Thompson et al.
8021380 September 2011 Thompson
8034095 October 2011 Randolph
8062307 November 2011 Sepetka et al.
8545499 October 2013 Lozier
8784434 July 2014 Rosenbluth
8814892 August 2014 Galdonik
8852205 October 2014 Brady et al.
9131988 September 2015 Bagwell
9138307 September 2015 Valaie
9194114 November 2015 Petry
9216034 December 2015 Avneri
9217243 December 2015 Gwen
9220499 December 2015 Viola
9717519 August 2017 Rosenbluth
2004/0215222 October 2004 Krivoruchko
2006/0184194 August 2006 Pal
2006/0287667 December 2006 Abela
2007/0066991 March 2007 Magnuson
2007/0118165 May 2007 DeMello et al.
2008/0033423 February 2008 Peacock, III
2008/0167678 July 2008 Morsi
2008/0262495 October 2008 Coati
2011/0144671 June 2011 Piippo Svendsen
2012/0005849 January 2012 Tash
2012/0172656 July 2012 Walters
2014/0135814 May 2014 Sepetka et al.
2014/0371782 December 2014 Galdonik et al.
2015/0119896 April 2015 Krolik
2016/0051261 February 2016 Centeno
2016/0221050 August 2016 Beck
2017/0311966 November 2017 Ben-Ami
2571343 Feb 2006 CA
1216929 May 1999 CN
1501825 Jun 2004 CN
2459481 Oct 2009 GB
2003-010193 Jan 2003 JP
2003-038500 Feb 2003 JP
WO 2005/102184 Nov 2005 WO
WO 2012/110619 Aug 2012 WO
WO 2013/105099 Jul 2013 WO
WO 2016/120864 Aug 2016 WO
Supplementary European Search Report and the European Search Opinion dated May 11, 2015 From the European Patent Office Re. Application No. 13735641.6. cited by applicant .
International Search Report and the Written Opinion dated Jul. 19, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050049. cited by applicant .
International Preliminary Report on Patentability dated Jul. 24, 2014 From the International Bureau of WIPO Re. Application No. PCT/IL2013/050049. cited by applicant .
Notification of Office Action and Search Report dated Dec. 4, 2015 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201380005571.8 and Its Summary of Office Action in English. cited by applicant .
Communication Pursuant to Article 94(3) EPC dated Mar. 10, 2016 From the European Patent Office Re. Application No. 13735641.6. cited by applicant .
Notification of Office Action dated Jul. 5, 2016 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201380005571.8. cited by applicant .
Patent Examination Report dated Sep. 7, 2016 From the Australian Government, IP Australia Re. Application No. 2013208660. cited by applicant .
International Search Report and the Written Opinion dated Jul. 29, 2016 From the International Searching Authority Re. Application No. PCT/IL2016/050073. cited by applicant .
Translation of Notification of Office Action dated Jul. 5, 2016 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201380005571.8. cited by applicant .
Invitation to Pay Additional Fees dated May 9, 2016 From the International Searching Authority Re. Application No. PCT/IL2016/050073. cited by applicant .
Notice of Reasons for Rejection dated Nov. 15, 2016 From the Japan Patent Office Re. Application No. 2014-551729 and Its Translation Into English. (18 Pages). cited by applicant .
Communication Pursuant to Article 94(3) EPC dated Jun. 23, 2017 From the European Patent Office Re. Application No. 13735641.6. (5 Pages). cited by applicant .
Notice of Reasons for Rejection dated May 30, 2017 From the Japan Patent Office Re. Application No. 2014-551729. (5 Pages). cited by applicant .
Translation of Notice of Reasons for Rejection dated May 30, 2017 From the Japan Patent Office Re. Application No. 2014-551729. (11 Pages). cited by applicant .
International Preliminary Report on Patentability dated Aug. 10, 2017 From the International Bureau of WIPO Re. Application No. PCT/IL2016/050073. (9 Pages). cited by applicant .
Translation of Decision of Rejection dated Dec. 12, 2017 From the Japan Patent Office Re. Application No. 2014-551729. (4 Pages). cited by applicant .
Decision of Rejection dated Dec. 12, 2017 From the Japan Patent Office Re. Application No. 2014-551729. (2 Pages). cited by applicant.
This application is a Continuation-In-Part (CIP) of PCT Patent Application No. PCT/IL2013/050049, having International Filing Date of Jan. 15, 2013, which claims the benefit of priority under 35 USC 119(e) of U.S. Provisional Patent Application No. 61/586,792 filed Jan. 15, 2012. The contents of the above applications are incorporated herein by reference in their entirety.
1. A device for use within an occluded biological vessel comprising an elongated body having a plurality of projections attached around a distal portion of said elongated body, said plurality of projections are folded against said elongated body when advanced distally through an occlusion in the biological vessel and self expand radially outward when the device is positioned within an occlusion in the biological vessel and pulled in a proximal direction, wherein each of said plurality of projections includes a leaf-like structure having a length and a width, said leaf-like structure having an inward curving distal tip and is concave along its width thereby forming a recess surrounded by upward curving walls when said projections are expanded radially outward in the biological vessel to thereby scoop a material forming said occlusion and further wherein each of said plurality of projections is connected to a stem portion having a higher axial rigidity than said leaf-like structure.
2. The device of claim 1, wherein said projections are angled with a distal tip thereof pointed in a direction of device pulling.
3. The device of claim 1, wherein said stem portion includes a protrusion for increasing said axial rigidity of said stem portion.
4. The device of claim 1, wherein said stem portion of each of said projections includes a protrusion for increasing friction of said projections.
5. The device of claim 1, wherein said projections are arranged as pairs along said distal portion.
6. The device of claim 5, wherein each pair of said projection is connected to said elongated body via a swivel.
7. The device of claim 5, wherein each pair of said projections is fixed to said elongated body at an angle rotated 0-90 degrees from an adjacent pair of said projections.
8. The device of claim 7, wherein said projections can be pushed and embedded within thrombus material when folded against said elongated body.
9. The device of claim 8, wherein said projections are capable of dislodging and/or collecting said thrombus material when said projections are embedded within said thrombus and said elongated body is pulled in a proximal direction.
10. The device of claim 1, wherein said stem portion includes an element for increasing said rigidity of said stem portion.
11. The device of claim 10, wherein said element is a thickened region or a strut.
12. The device of claim 1, wherein said leaf-like structure and said stem portion are composed of silicone and further wherein said stem portion is composed of a higher Shore silicone.
13. The device of claim 1, wherein said inward curving distal tip is capable of embedding within said occlusion and facilitating self expansion of said projections when the device is pulled in said proximal direction.
14. The device of claim 1, further comprising two imaging markers at least one of which being attached to said elongated body via an arm extending radially outward from said elongated body.
15. The device of claim 1, further comprising a lumen extending between a distal end and a proximal portion of the device, said lumen being for enabling blood flow around an occlusion in a blood vessel when the device is positioned in said blood vessel with said distal portion within said occlusion.
In the distal approach, the distal end of the retrieval device (typically fitted with a distal basket or snare) is passed through the occlusion and positioned at a distal side thereof. The device is then pulled back (in a proximal direction) while the distal end engages the thrombus material. One example of a commercially-available device employing this approach is the Merci retriever, manufactured by Concentric Medical Inc. and described in U.S. Pat. No. 6,663,650.
According to still further features in the described preferred embodiments the leaf-like portion of the projections may be concave thereby enabling the leaf-lie portion to function as a scoop.
According to still further features in the described preferred embodiments the projections are arranged as single, pairs or more along the distal portion.
According to still further features in the described preferred embodiments the device is deliverable into the biological vessel through a 1.5-60 F sheath.
According to still further features in the described preferred embodiments the strut is a nitinol strut, thicker embodiment or enhanced structure.
According to still further features in the described preferred embodiments the leaf-like structure and the stem portion are composed of elastomeric material such as thermoplastic elastomers (TPEs), silicone, other plastics or metal alloys such as Nitinol and further wherein the stem portion is composed of a higher rigidity material, different material or combination of materials.
According to another aspect of the present invention there is provided a method of removing a thrombus from a blood vessel comprising: (a) positioning in the blood vessel a device including a plurality of projections, each of the plurality of projections includes a leaf-like structure connected to a stem portion having a higher axial rigidity than the leaf-like structure; and (b) advancing the plurality of projections distally into a thrombus material; and (c) pulling the projections proximally to thereby penetrate, engage, dislodge and collect the thrombus material.
The present invention successfully addresses the shortcomings of the presently known configurations by providing a device for effectively and non-traumatically clearing occlusions in vessels such as blood vessels.
FIGS. 2-3 illustrate a pair of projections in a side view (FIG. 2) and an isometric view (FIG. 3).
FIGS. 6A-B illustrate various embodiments of projections which are angled with respect to the device body.
FIG. 7A illustrates an embodiment of the present device having the projections of FIG. 6A.
FIGS. 8A-B illustrate a prototype of the device of the present invention with reinforced (FIG. 8A) and non-reinforced (FIG. 8B) projections.
FIGS. 9, 10, 11 and 12 illustrate bench testing of the prototypes of FIG. 8A-B.
FIGS. 13A-H illustrate a thrombectomy procedure conducted in a pig using a prototype device constructed in accordance with the teachings of the present invention.
FIGS. 14A-F are angiograms illustrating results of a pig study conducted with the present device and a prior art thrombectomy device.
FIGS. 15A-F are histology slides of arteries catheterized with the present device (FIGS. 15A-C) and a Nitinol thrombectomy device (FIGS. 15D-F).
In order to maximize thrombus material penetration and dislodgement, catheters having clot retrieval heads which include a plurality of discrete projections have been developed (e.g. U.S. Pat. Nos. 5,895,400, 7,731,731, 5,702,413, 5,827,304, 6,350,271, 6,692,504 or 7,008,434); however, such catheters may be less effective for retrieving thrombus material or minimizing damage to the vessel wall.
The device includes an elongated body for delivering a plurality of projections arranged around a distal portion of the elongated body into the biological vessel. The device can be configured as a catheter for use with a guidewire in clearing thrombus material from a blood vessel. When configured as a catheter, the elongated body can include a longitudinal lumen sized for accepting a guidewire (e.g. 0.014'', 0.018'' or 0.035'' or other guidewires). The lumen can be configured for use with over-the-wire, or rapid exchange systems.
The elongated body can be 10 to 200 cm in length with a width/diameter of 0.5-20 mm when in closed configuration (suitable for delivery within a 1.5-60 F sheath). The elongated body is preferably shaped as shaft (rod or tube) and is fabricated from any bio-compatible material, including, for example, alloys such as stainless steel, Nitinol or polymers such as Polyimide (PI), Polyether Block Amide (PEBA)--Pebax. The elongated body is preferably axially rigid in order to facilitate lodging of the distal portion (carrying the projections) into the occlusion and yet flexible enough to facilitate navigation through torturous vessels while ensuring safety (e.g. blood vessels in the brain). Rigidity of the elongated body (catheter) is same range as catheters commonly used for navigating biological vessels such as blood vessels.
Each projection includes a leaf-like structure connected to a stem portion having a higher axial rigidity than the leaf-like structure. Any number of projections can be carried on the elongated body depending on the biological vessel, occlusion size and type and function of the device. A typical number of projections can range from 1-20 or more.
The axial rigidity of the stem portion can be preferably anywhere from 0.1-100 grams (e.g. 10-90, 20-80, 30-70, 40-60) or more depending on the occlusion location, occlusion type and size, leaf like structure and material the stem is constructed from. The axial rigidity of the leaf like structures can preferably be anywhere from 0.0-50 grams (e.g. 5-40, 10-30, 20-25) or more depending on the occlusion location, occlusion type and size, leaf like structure and material the leaf is constructed from.
The leaf-like structure can be of any shape and size suitable for collection of occlusion material. The leaf-like structures can be oval-shaped, rectangular/polyangular-shaped, spiral, a combination of several shapes including simple or complex shapes with fractal characteristics.
Typical dimensions for the leaf-like projections can be 0.2-30 millimeter in length, 0.05-20 millimeter in width, 0.03-3 millimeter in thickness, with a single side surface area of 0.01-600 millimeter.sup.2.
The internal surface (facing towards the elongated body) of the leaf-like structure is preferably concave in order to increase the surface area thereof and the drag/resistance force exerted on the internal surface by the thrombus mass. Such a concave configuration also increases the ability of the projections to collect (scoop) the occlusion material. The exterior surface of the leaf-like structure is preferably convex to facilitate delivery within the vessel and lodging of the projections into the occlusion while folded in a "close configuration" (arrow like) due to the drag forces exerted on the leaves-like by the occlusion material when the projections are advanced into the occlusion. Although such a configuration is preferred, internal and external surfaces having alternative contours (e.g. flat on both sides) are also envisaged herein. Each leaf-like structure can also fold in half lengthwise to further improve penetration into the occlusion material.
The internal surface of the leaf-like structures can also include projections (nanometers to millimeters in height) to increase the surface area and enhance interaction between the leaf-like structures and the occlusion material. Such projections can be simple protrusions or branching, "fractal-like" protrusions which significantly increases the surface area in contact with the thrombus material. The protrusions can project at an angle of 90 degrees or less from the surface and take the form of individual cones, hairs, spines or the like. The protrusions can also be arranged as overlapping scales or as continuous ridges. The protrusions can also form a Gecko-like surface (Menguc and Sitti "Gecko-Inspired polymer Adhesives", Polymer Adhesion, Friction, and Lubrication, First Edition).
The internal surface of the leaf-like structures can also include depressions (e.g. pores, channels). In any case, the protrusions or depressions can be an order of magnitude smaller than the size of the leaf-like structure (e.g. protrusions in a leaf-like structure 10 mm long can be 1 mm in length).
The protrusions/depressions can be arranged in a fractal-like order with a parent protrusion/depression surrounded by scaled-down protrusions/depressions. For example, a 10 mm long leaf-like structure can include 1 mm long primary protrusion surrounded by several "sub-protrusion" that are 0.1 mm in length (and so forth).
Such structuring of the internal surface of the leaf-like structures can improve complete retrieval of the thrombus in its in-situ form and thus can minimize the risk of embolism as a result of particles "escaping" from the thrombotic mass.
The distal portion (tip) of the leaf-like structure is preferably curved inward in order to minimize trauma/damage to the vessel when the device is navigated within the blood vessels. To further decrease trauma and irritation to the vessel wall, the tips can be fabricated from a very soft material (softer than the rest of the leaf-like structure).
The inward curving tips can also facilitate hooking of the projections into the occlusion material.
(i) Delivery and penetration of occlusion material--when the present device is advanced in a distal direction the contour of the external surface and elasticity of the leaf-like structures enable folding of the projections which reduces the profile of the device and also streamlines the outer surface of the folded projections. This enhances delivery and minimizes disruption of the occlusion (which can lead to release of embolic particles).
(ii) Engagement/anchoring of occlusion material--when the present device is pulled in a proximal direction, drag forces are applied to the inner surfaces of the leaf-like structures and cause the projections to open. This increases the cross sectional area of the device and its surface interaction with the occlusion. In addition, exposure of the inward curving tips to the occlusion material, increases penetration and lodging of the projections in the occlusion material. The stem portion prevents the projections from flipping over thereby ensuring that a pulling force at the handle/proximal part of the device is efficiently converted to engagement/anchoring force.
(iii) Dislodgement of occlusion material--the pulling force at the handle/proximal part of the catheter is also efficiently converted to a proximal movement of the catheter-occlusion complex. The projections can be designed such that the forces applied thereby are matched to the type and location of occlusion. The forces applied by the projections on the occlusion are a function of the occlusion material, size and the properties of the occlusion and the vessel surrounding it, thus minimizing unnecessary force and distortion of the thrombus natural configuration.
(iv) Removal of occlusion--the increased surface area, and the multiple contact areas (at plurality of projections), as well as the unique scoop-like shape of the internal surface of the leaf-like structures facilitate collection of dislodged material. The occlusion material is trapped by the device (projections) creating a catheter-thrombus complex that can be removed as one piece.
The present invention is described in greater detail hereinbelow with reference to the embodiment shown in FIGS. 1-4.
Referring now to the drawings, FIGS. 1-4 illustrate one embodiment of the present invention which is referred to herein as device 10.
Projections 18 are preferably arranged as single or pairs (arrangements including 3, 4, 5, 6 or more projections are also possible) around distal portion 20, with each single or pair rotated 0-180 degrees from an adjacent single pair. FIG. 4 is a frontal view of device 10 showing two pairs of projections 18 arranged with a 90 degree rotational offset between pairs.
FIGS. 2-3 illustrate one pair of projections 18 in greater detail. Each projection 18 includes a stem portion 22 which is attached to a leaf-like structure 24. As is mentioned hereinabove, the axial rigidity of stem portion 22 is greater than that of leaf-like structure 24. Such increased axial rigidity can be achieved by fabricating stem portion 22 from a more rigid material, by making stem portion 22 thicker than leaf-structure 24 or by providing stem portion 22 with a rigidifying strut (e.g. Nitinol/stainless steel strut co-molded with stem portion 22). In the embodiment shown in FIGS. 1-4, stem portion 22 includes a thickened portion 26 which serves to both increase rigidity thereof and limit the angle of stem portion 22 with respect to the longitudinal axis of elongated body 12, such that outward deployment of projections 18 is limited to a preset angle .alpha. (FIG. 2) set by portion 26. Portion 26 is also rigid enough to prevent projections 18 from flipping over (angling towards the distal direction).
As is shown in FIGS. 2-3, leaf-like structure 24 includes an inward curving tip 34 for minimizing damage or irritation to the vessel wall when device 10 is pushed and pulled within the vessel. Inward curving tip 34 also functions to facilitate lodging of projections 18 into occlusion material (e.g. thrombus material) when device 10 is pulled in a proximal direction.
As is shown in greater detail in FIG. 3, leaf-like structures 24 are preferably concave (C) at an internal surface thereof and convex (X) on the opposite surface. When in proximal movement after engaged to the thrombus mass the concave shape of the inner surface allows a higher surface contact area and higher drag forces. In addition, leaf-like structure 24 scoops the occlusion material dislodged from the vessel wall.
When moving distally and penetrating the thrombus mass the convex shape produces less drag forces. The concave shape also allows projections 18 to fold into a compact streamlined configuration for delivery into the vessel and occlusion. Additional hydrodynamic streamlining of projections 18 may be effected by providing the outer surface thereof with one or more bumps/protrusions/channels etc. Projections 18 can be individually attached to elongated body 12 via gluing or mechanical couplers. Preferably, projections 18 are attached to elongated body 12 via a fixed or swivel coupler or via molding. For example, two stem portion 22 can be co-molded with a cylindrical coupler 32 (FIG. 3) which can be fitted around elongated body 12 and fixedly attached thereto or allowed to swivel. Leaf-like projections can then be glued or mechanically coupled to the distal end of stem portions 22--or just molded as one piece from the same material.
Projections 18 can be fabricated from a single material or from two or more materials. For example, in the embodiment shown in FIGS. 1-4, projections can be molded from a single material (e.g. silicone, teflon, nylon and any other elastomer, metal alloys such as Nitinol or elastomer with combination with metal alloys such as Nitinol), with the differential rigidity provided by varying the durometer of the material (e.g. molding stem portion 22 from a different structure, a silicone having a higher Shore A value or increased thickness, or by using a different material or a combination of different materials).
As is mentioned hereinabove, the embodiment of device 10 of FIGS. 1-4 is configured for use in clearing obstructions in a blood vessel, preferably a small brain artery that is 0.5-7 millimeter in diameter. As such, elongated body 12 of device 10 is preferably 10-200 centimeter in length, 0.5-7 millimeter in diameter when in closed configuration, while projections 18 are preferably 0.2-30 mm in length. The length of leaf-like structures is preferably 0.1-30 mm and the width (at the widest thereof) is preferably 0.05-20 mm. Stem portion 22 is preferably 0.1-20 mm in length and 0.02-20 mm in width (at the base).
Projections 18 can be folded against elongated body 12 to an overall diameter of 0.5-7 millimeter. When folded, device 10 can be packed into a 1.5-60 F sheath for delivery through an access site. Once pushed out of the sheath, projections 18 are folded outward to a position constrained by stem portion 22 (or vessel wall) while distal portion 20 is advanced to the site of occlusion. Since leaf-like structure 24 includes a non-traumatic tip 34, advancing device 10 in the distal direction (towards occlusion) does not traumatize or irritate the vessel wall. Once in position, pulling on handle/proximal catheter part 14 deploys projections 18 to angle a as limited by stem portions 22 or the vessel wall. In the deployed position, leaf structures 24 are displaced up to 90 degrees (or more) from the longitudinal axis of elongated body 12 (as limited by stem portion 22) to nearly contact or contact the wall with tip 34 angling inward to eliminate trauma and irritation to vessel wall.
The flexible nature of the leaves-like permits the device to automatically adapt to the caliber of the blood vessel in which device 10 is situated.
Stem portion 22 and/or leaf-like structure 24 can also be configured such that when folded against elongated body 12, the longitudinal axis of leaf like structure 24 is angled with respect to the longitudinal axis of elongated body 12 (FIGS. 6A-B). This increases the exposure of the internal surface to the biological fluid in the vessel and to the occlusion material and increases drag and likelihood of deployment when device 10 is pulled in a proximal direction.
FIGS. 6A-B illustrate alternative angulations of projections 18. As is shown in
FIG. 6A, projections 18 can be angled laterally (angle range 0-90 degrees) relative to the device main long axis (yaw). This will prevent full symmetry and overlapping of the leaves when in closed configuration and in backward (proximal) movement. The lack of symmetry exposes the inner surface area of leaf-like structures 24 to the occlusion to initiate opening of projections 18. A device 10 having such projections 18 is shown in FIG. 7A.
A roll angle can also be added such that each leaf-like structure 24 has an "angle of attack" (FIG. 6B) relative to the movement vector (angle range 0-90 degrees) i.e. to the anterior edge of leaf-like structures 24 relative to movement of device 10. The angle of attack in the forward motion (when device 10 is pushed towards occlusion) will have hydrodynamic features and a curve design that will ensure an ability to optimally penetrate and minimally disrupt the thrombus structure.
When the device is pulled proximally, the angle of attack (which is the opposite edge) can be shaped in a more acute curve structure in order to allow optimal drag forces of the thrombus on each leaf-like structure 24 thereby ensuring opening of projections 18. Projections 18 can also be configured to spiral around elongated body 12 as is shown in the example of FIG. 7B.
The size shape and properties of projections 18 can be configured according to the blood vessel and occlusion properties. There are two type of thrombus occlusions, a `red` thrombus (fresh, acute whole blood thrombus) and a `white` thrombus (relatively chronic embedded with cholesterol and calcium). Projections 18 of device 10 have rigidity properties at a range matching the viscosity ranges of the thrombus.
In cases where delivery is effected through a catheter or guide tube (guiding catheter), delivery and navigation of device 10 can be effected without a guidewire.
In any case, handle 14 (or proximal portion of elongated body 12) is used to guide device 10 (whether over a wire or not) through the vessel and position distal portion 20 at a site of occlusion.
Use of device 10 in clearing a thrombus in a blood vessel is described in greater detail below with reference to FIGS. 5A-D.
Markers 31 can be mounted on ends of foldable arms 33 (e.g. Nitinol, platinum, other metal alloy or polymer wires) extending radially outward from elongated body 12 (FIG. 2). When distal portion 20 is positioned outside of the occlusion, markers arms 33 extend out and thus when visualized (fluoroscopy) markers 31 are a predetermined distance apart (e.g. several millimeters). When distal portion 20 is positioned inside an occlusion, markers arms 33 fold against elongated body 12 and thus when visualized (fluoroscopy) the distance between markers 31 is reduced.
Marker material (e.g. iridium or platinum) can also be included in the material used to fabricate projections 18 or leaf-like structures 24 in order to facilitate identification thereof by a surgeon.
In any case, the markers assist the clinician in determining the correct placement of device 10 within a blood vessel and indicate when distal portion 20 enters an occlusion and projections 18 are lodged therein.
Device 10 of the present invention can be used to clear any type of occlusion in any vessel. FIGS. 5A-D illustrate use of device 10 in clearing a thrombus in an artery.
A guide catheter or guidewire is advanced from an access site (e.g. in a femoral artery) to the carotid artery under angiography. Device 10 is then inserted over-the-wire or through the guide catheter and navigated to the site of the thrombus (FIG. 5A). The surgeon then advances the distal end of device 10 into the thrombus (FIG. 5B) until the distal end of device 10 reaches the distal end of the thrombus (as visualized via the radio-opaque markers described above). The surgeon then applies a gentle pulling force on device 10 to open projections 18 and lodge and engage/anchor them within the thrombus. The device is then pulled along with the trapped thrombus (FIG. 5C).
Several prototypes of the device of the present invention were constructed by mounting 4 pairs of 30 mm long and 8 mm wide silicone projections (10 mm stem portion and 20 mm leaf like structure) on a stainless-still rod 1 millimeter in diameter. Two types of projections were tested, `soft` projections fabricated from 70 Shore silicone (FIG. 8B) and reinforced projections fabricated from 70 Shore silicone and including a 20 mm plastic strut fixed to the stem portion and a portion of the leaf-like structure of each projection (FIG. 8A). Two configurations of projections were tested, pairs arranged with a 90 degree rotational offsets, and pairs arranged with a 45 degree rotational offset.
The total diameter of the device was 25 mm when the projections were in the open configuration (FIG. 8A) and 10 mm when in the closed configuration (FIG. 8B).
Fresh human venous blood was drawn from cubital fossa vein and was mixed for 10 seconds with human thrombin (BioPharm Laboratories, LLC, Bluffdale, Utah, USA) at a ratio of 25 IU to 10 ML whole blood and was incubated for 60 minutes at room temperature inside cylindrical transparent tubes having the following dimensions:
Each device prototype (FIG. 9) was advanced into the tube to penetrate the proximal clot mass until the distal tip of the device reached the distal (end) of the clot mass (FIG. 10).
(i) four with the "enforced" catheter prototype: 3.times.25 millimeter thrombus diameter and 1.times.20 millimeter thrombus diameter; and
(ii) two with the "soft" catheter prototype: 2.times.20 millimeter thrombus diameter
It was observed that while penetrating the clot mass, the projections folded into a closely packed configuration (FIG. 11).
The device prototypes were then pulled in the proximal direction dislodging the clot mass and collecting it out of the tube (FIG. 12).
An 80 Kg female swine was anesthetized and a mid-line laparotomy was conducted to expose the retro peritoneal space and allow aortic puncture. A 16 F introducing sheath was delivered into abdominal infra-renal aorta using the Seldinger approach.
A thrombus measuring approximately 2 cm in length and 5 mm in diameter was prepared from autologous whole blood incubated with Barium (10 cc whole blood to 1 g of Barium sulfate) for two hours at room temperature using a method previously described by Kan L, et al. A novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy devices. AJNR Am J Neuroradiol. 2010 October; 31(9):1741-3). The thrombus was introduced into the sheath and delivered into the left internal iliac artery under fluoroscopy (FIG. 13A).
An occlusion of the left internal iliac artery was demonstrated via angiography (FIG. 13B).
A prototype catheter was fabricated using a 70 Shore silicone mixed with 10% radio opaque Barium sulfate. The prototype length was 42 mm with a diameter in its neutral configuration measured 5 mm. The prototype included 8 pairs of 5 mm long leaf-like projections.
The catheter was navigated over a guidewire and into the occluded vessel and thrombus under fluoroscopic guidance. Approximately one minute following engagement between the catheter head and the thrombus, the catheter was gently pulled back (proximately) under fluoroscopy and retrieval of the thrombus material was observed. The catheter with engaged thrombus material were pulled into the introducing sheath (FIGS. 13C-E) and then removed from the artery (FIG. 13F). The thrombus material was visualized engaged to the catheter head outside the body (FIG. 13G).
A control angiography demonstrated that the occlusion was removed and that blood flow was restored to the left internal iliac artery with no filling defects. A moderate yet smooth narrowing of the vessel was demonstrated as a result of a moderate vasospasm which resolved later (FIG. 13H).
A pig study was conducted in order to demonstrate the safety feature of the present device during artery passage and to compare device safety with Nitinol spiral-shaped stent retriever commonly used in thrombectomy procedures.
An 81 Kg female swine was anesthetized and a mid-line laparotomy was conducted and the retro peritoneal space was exposed to allow aortic puncture. The Seldinger's technique was used to deliver a 16 F introducing sheath into the abdominal infra-renal aorta to enable subsequent arterial access and catheterizations of the target vessels. The anatomy of the distal aorta, iliac and femoral arteries was demonstrated via angiography (FIGS. 14A and 14C) and the internal diameter (ID) of the target arteries was measured using standard calibrated techniques. The following arteries were used for the procedures:
(i) Right External Femoral artery (distal) (T1); average ID 4.2 mm--present device
(ii) Right Internal (Deep) Femoral artery (T2); average ID 4.0 mm--nitinol based device
(iii) Left Internal (Deep) Femoral artery (T3); average ID 4.2 mm--present device
(iv) Left External Femoral artery (distal) (T4); average ID 4.2 mm--nitinol based device
The present device was fabricated from a 70 Shore silicone and was 5 mm in diameter with projections in the open (neutral) configuration; the recommended target vessel ID: 4.0-5.0 mm. The Nitinol based device: was 6 mm diameter in the open configuration; recommended target vessel ID: 3.0-5.5 mm.
The present device was guided over the wire through a 16 F introducer and into the target vessels (T1 and T3) under fluoroscopy using standard catheterization technique. Three consecutive forward and backward passes were made in the target vessels.
The Nitinol based device was guided through a 16 F introducer and into the target vessels (T2 and T4) under fluoroscopy using standard catheterization technique. Three consecutive backward passes were made in the target vessels while the device was in an open configuration. Forward repositioning of the device was made following re-sheathing of the device into a micro-catheter.
The target vessels were surgically removed, flushed and fixed in formaldehyde, and marked with proximal and distal markers.
The excised vessels were sent to a pathology laboratory for Histological analysis primarily of the endothelial layer and the internal elastic lamina of all samples.
A control angiography was performed following catheterization of each target vessel. Minimal to mild vasospasm was observed in arteries T1, T3 (present device, FIGS. 14B and E) and a severe vasospasm was observed in arteries T2, T4 (Nitinol device, FIGS. 14C and F).
The excised blood vessels appeared to be within normal ranges. Occasional foci of hemorrhage were present in the adventitia. A semi-quantitative histological assessment was employed. Samples were evaluated for endothelial erosion, fibrin deposition, thrombus formation, continuity of the internal elastic lamina (IEL), medial lesions (tearing, necrosis, and inflammation) and lesions in adventitia. The specific parameters were scored as shown in Table 1 below (unless otherwise indicated): 0=Absent, 1=Minimal, 2=Mild, 3=Moderate or 4=Severe.
TABLE-US-00001 TABLE 1 Semi-quantitative scoring of artery lesion parameters Scored 0 1 2 3 4 Parameter (none) minimal mild moderate severe Endothelial Loss Intact <10% of the 10-40% 40-75% >75% endothelium vessel circumference Internal elastic Normal Focal Focal tear of Tear of IEL Multiple areas lamina disruption of IEL with with of tearing of IEL fibrin hemorrhage IEL deposition and or inflammation and or early thrombus formation Medial Changes Normal Focal Focal Locally Mural tear with severity of lesion piknosis necrosis extensive hemorrhage (pressure with necrosis with inflammation necrosis) hemorrhage, hemorrhage or minimal and moderate leukocyte leukocyte infiltration infiltration Medial Changes Normal <25% of the 25-50% 51-75% >75% (% of vessel vessel circumference) circumference Adventitia, Normal <25% of the 25-50% 51-75% >75% necrosis/tearing vessel circumference
Table 2 below summarizes the histological findings for samples T1-T4
TABLE-US-00002 TABLE 2 Semi-quantitative analysis of pathologic changes in the artery Endo- Media Sample Cut thelium IEL Media circumference Adventitia T1 1 0 0 0 0 0 2 0 0 0 0 0 3 1 0 0 0 0 4 1 0 0 0 0 5 1 0 0 0 0 6 1 0 0 0 0 T2 1 4 0 0 0 0 2 4 0 0 0 0 3 4 1 1 1 0 4 4 1 1 1 0 5 3 0 0 0 0 6 2 0 0 0 0 T3 1 0 0 0 0 0 2 0 0 0 0 0 3 1 0 0 0 0 4 0 0 0 0 0 5 0 0 0 0 0 6 0 0 0 0 0 T4 1 1 0 0 0 0 2 1 0 0 0 0 3 2 0 1 1 0 4 4 0 0 0 0 5 4 0 0 0 0 6 1 0 0 0 0
T1--There was minimal epithelial sloughing in cuts 3 to 6, involving less than 5% of the lumen circumference, with no evidence of thrombus formation. Overall, the artery was within normal ranges.
T2--sloughing of the endothelium was observed in all cuts. In cut 3 there was a single focus of apparent loss of continuity of the IEL with focal piknosis of underlying smooth muscle in the tunica media, and focal pale staining of the cytoplasm, suggesting acute necrosis. In cut 4 there was similar loss of continuity of the IEL with focal piknosis of smooth muscle. However, there was no evidence of leukocyte infiltration, and no fibrin deposition or early thrombus formation. The areas of loss of continuity of the IEL were confirmed on elastica stain. The arterial wall appeared to be within normal ranges in all remaining cuts.
T3--There was minimal epithelial sloughing in cuts 3 to 6, involving less than 5% of the lumen circumference, with no evidence of thrombus formation. Overall, the artery was within normal ranges.
T4--Cuts 1, 2, 3 and 6 were within normal ranges with minimal endothelial sloughing in foci. In cut 4 there was moderate endothelial sloughing with continuity of the IEL and a single focus of piknosis and pale staining of smooth muscle cells, suggesting acute pressure necrosis. There was however no evidence of leukocyte infiltration. Complete endothelial sloughing was observed in cuts 4 and 5.
Catheterization with the present device resulted in intact endothelium (FIG. 15A, arrows), a continuous IEL (FIG. 15B) and only two small foci of endothelium erosion covering less than 5% of the lumen circumference (FIG. 15C, arrows). On the otherhand, catheterization with the Nitinol device resulted in extensive endothelial erosion (FIG. 15D, arrows), loss of continuity of the IEL (FIG. 15E, arrow) and a single focus of endothelial necrosis (FIG. 15F, arrow).
Thus, catheterization using the present device minimally impacted the integrity of the vessel wall, while on the otherhand, catheterization using the Nitinol device resulted in widespread erosion of the intima, pressure necrosis and disruption of the IEL.
Previous Patent US 9,987,026 | Next Patent US 9,987,028