CA2120918A1

CA2120918A1 - Flow directed catheter

Info

Publication number: CA2120918A1
Application number: CA002120918A
Authority: CA
Inventors: Wendy J. Zenzen; Uriel Hiram Chee
Original assignee: Individual
Current assignee: Target Therapeutics Inc
Priority date: 1993-02-25
Filing date: 1994-02-24
Publication date: 1994-09-01
Also published as: EP0637935A4; FI945001A0; NO944047D0; FI945001A; IL108755A0; JPH07505559A; AU6274894A; US5336205A; NO944047L; WO1994018886A1; NZ262835A; AU672686B2; EP0637935A1; TW240173B

Abstract

An infusion catheter (100) with an elongate tubular body having proximal and distal ends and a lumen extending between the ends through which a diagnostic, therapeutic, or vaso-occlusive agent can be delivered, is disclosed. The elongate tubular body is formed of a relatively stiff tapered proximal segment (122), a relatively flexible and strong distal segment (120), and a transition section (124) that is less flexible than the distal segment but more flexible than the proximal segment. The infusion catheter is directed to the target site by means of the flow of blood to that site.

Description

WO 94/18~86 PCrlUS94/02249 -1- 2l2o9l8 FLOW DIRECTED C.ATHETER

Field of_~Q Invention The present invention i in the general field of surgical in~truments and relates ~pecifically to infusion catheter~ that are uqed in cardiovascular and endovascular pro~edure~ to deliver diagnostic, therapeutic or vasoocclu3ive agents to a target site (the target site being accessible by a tortuou~ path through the vasculature). The invention also relates to the process of using the infusion catheter.

Background Catheters are being used increasingly as a means for dalivering diagnostic or therapeutic agent~ to internal target 8ite8 that can be acceQsed through the circulatory system. ~here are a number of general approaches for placing catheters within ves els in the body that are difficult to acces~. In one such techuique, a torqueable guidewire i8 alternately rotated and advanced to the target 8ite. With the w~re in place, the catheter i8 then advanced along the wixe u~til the distal end of the catheter i~ positioned at the target site. An example of this technique i~ de3cribed in U.S.
Patent No. 4,884,579. A major draw~ack to this approach ' i8 the time-consuming nature of rotating and advancing the guidewire and catheter through the vasculature.
A second technique for ad~ancing a catheter to a target site is to employ a highly flexible catheter having an inflatable, but pre-punctured balloon at its WO ~/l~UK PCT~4/OZ~9 212091~ ~
distal end. In use, the balloon is partially inflated, and carried by blood flow into the target site. During placement, the balloon is continually inflated to replenish fluid leaking from the balloon. Thi~
S technique, too, has major drawbacks including the ~act that the catheter material is so floppy that it cannot be pushed without buckling, and instead must be ad~anced using injected fluid to inflate the balloon in order to propel the catheter to the target site. Additionally, 10 there i8 a significant risk of rupture of a vessel by a balloon that has been overinflated.
In order to addre~s some of the above described problems, another approach has involved the use of flexible catheters that can be directed to a target site 15 as a result of the blood flowing to that site. In 1991, Target Therapeutics released a product known as the "ZEPHYR" flow-assisted infusion catheter. The product was designed to be introduced into the ~asculature through a guiding catheter and then allowed to be 20 directed by the blood flow to a target site. The catheter comprised segments of different materials, a proximal segment made of nylon, and middle and distal segments made of a block copolymer of polyamide. The product proved to be unsuccessful in achieving its 25 desired function as it was not flexible enough to navigate the tortuous vessel pathway and not strong enough to withstand the required injection pressure.
~ The present invention is an infusion catheter j assembly useful for the delivery of diagnostic, 30 therapeutic or vasoocclusive agents to remote portions of the vascular system, particularly to diagnose or treat arteriovenous malformations (AVMs). The invention also 3 includes a process for placing the infusion catheter at the target site and a process for delivering a i ,, Wos4/1~6 PCT~S94/0~9 212091~
diagnostic, therapeutic or vasoocclusive agent to the target site.

Summary of the In~ention This invention is an infusion catheter fQr placement within a tortuous, small vessel pathway and a method for delivery of an agent to a target site. The infusion catheter is directed to the target site by means of the flow of blood to that ~ite. The infusion catheter has an elongate tubular body having proximal and di~tal ends and a lumen extending between the ends through which the diagnostic, therapeutic, or vasoocclusi~e agent can be delivered.
The elongate tubular body is formed of a relatively stiff tapered proximal segment, a relatively flexible and strong distal se$ment, and a transition section between the proximal and distal segments that is less flexible than the distal segment but more flexible than the proximal segment. The distal segment has a burst pressure of at least about 195 psi and is made of a material that will show a force of about lx10-4 or les~
when ten centimeters of the material i8 deflected 10 from horizontal.
A further aspect of the in~ention i8 a method for accessing a target site. A guiding catheter is inserted into the vasculature. An infusion catheter is then inserted into the guiding catheter. A ~tylet may optionally be used to ~traighten the soft, flexible distal end of the infusion catheter for easy in~ertion into the guiding catheter. If the ~tylet is used, it is removed once the infusion catheter is inside the guiding catheter. The infusion catheter is then pushed out of the guiding ca~heter into the ~asculature. The blood flow in the vasculature directs the infusion catheter to the target site.

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W094/1~C PCT~S94/0~9 212091~
Yet another aspect of the invention is a method for delivering a diagnostic, therapeutic or vasoocclusive agent to a target site. The infu~ion catheter i9 inserted into the vasculature by means of a guiding catheter. The infusion catheter is positioned at the target site a~ a result of the blood flow to the target site. The diagnostic, therapeutic or va~oocclusive agent is then injected through the catheter lumen and infused into the target site.
Brief Description of the Drawing~
FIG. 1 is a diagram that shows an infusion catheter constructed according to a preferred embodiment of the present invention.
FIG. 2 is a diagram that shows the distal end on one embodiment of the infusion catheter of the present invention wherein the distal end is formed in an "S n shaped configuration.
FIG. 3 is a diagram that shows an infusion catheter, stylet and guiding catheter as~embly.
FIG. 4 is an illustration of a portion of a tortuou~ path in a soft ti~sue, and the method of guiding the infusion catheter along this path.
FIG. 5 i~ a graph showing the pounds of force corresponding to the angle that the distal segment material of the inventive catheter is deflected a3 compared to the di~tal segment material of a prior art catheter.

Detailed De~cription of the Invention FIG. 1 shows an infu~ion catheter 100 constructed according to a preferred embodiment of the invention. The catheter 100 has an elongate tubular body 102 with proximal 104 and distal 106 ends and an inner lumen 108 extending between the end~. The elongate WO 94/18886 PCI~/US94/02249 -5- 21209'1~

tubular body 102 is comprised of three segments; a relatively flexible and strong distal ~egment 120, a relatively stiff tapered proximal segment 122 and a transition section 124 between the proximal and distal segments that is less flexible than the distal segment 120 but more flexible than the proximal segment 122.
The elongate tubular body 102 has a relatively flexible and strong distal segment 120 such that the catheter can easily navigate a tortuous ve~sel pathway.
~3y relatively flexible is meant that a force of about lx10-4 pounds corresponds to a deflection of the material that is 10 from horizontal, or only about sx1o~4 pounds of force to deflect the material about 80 from horizontal. By relatively strong is meant that the material has a burst pressure of greater than 195 psi, more preferably the burst pressure is between about 195 and 220 psi.
The flexible distal segment 120 has an open end which allows for the infusion of diaynostic, therapeutic or vasoocclusi~e agents into the target site. The s flexible distal 9egment 120 is made of a polymer that is ~! ' springy and biologically compatible such as polyurethane, a block copolymer of polyamide, polyvinyl chloride, or silicone or blends of the above. The flexible distal segment 120 carries one or more radiopaque bands 130 or may be doped with a radiopaque material such as barium sulfate, bis~th trioxide, bismuth subcarbonate, tungsten, tantalum or the like 80 that the location of the distal region of the catheter within the vessel may be visualized radiographically. The distal segment 120 makes up between about 5 and 25~ of the total length of the tubular member and i8 between about S and 40 cm long, preferably between about 10 and 20 cm long. The inner diameter of the distal segment 120 is between about 0.25 and O.S0 mm, more preferably between about 0.25 and 0.35 7~3~

WO ~/18UK PCT~S94/0~9 mm. The outer diameter of the distal segment is between about 0.S0 and 0.80 mm, more preferably between about O.60 and 0.70 mm. The wall thickness of the distal segment 120 is between about 0.1 and 0.3 mm.
S The proximal segment 122 of the elongate tubular body 102 is relatively stiff such that it can be easily pushed thus eliminating the need for guidewire support. The proximal segment 122 i9 made of a polymeric or metallic material that is relatively stiff and biologically compatible such as nylon, polyvinyl chloride, polyethylene terephthalate or other polyester elastomers or a braided shaft (a polymer outer core with a metallic mesh inner core). The proximal segment 122 comprises a tapered proximal section 134 for attachment to the proximal end fitting 150 and a distal section 132.
The proximal section 134 of proximal segment 122 makes up between about 60~ and 80% of the total length of the tubular member 102 and i8 between about 90 and 130 cm long, preferably between about 100 and 120 cm long. The largest inner diameter of the proximal section 134 (at the proximal end 104 of the tubular member 102) is between about 0.40 and 0.60 mm, more preferably between about 0.45 and 0.55 mm. The outer diameter of the proximal section 134 at the proximal end 104 of the tubular member 102 is between about 0.8 and 1.2 mm. The wall thickness of the proximal section 134 of prox;mal segment 122 is between about 0.1 and 0.4 mm, more preferably between about 0.2 and 0.3 mm.
The distal section 132 of proximal segment 122 makes up between 10 and 20~ of the total length of the tubular body 102 and is between about 20 and 40 cm long, preferably between about 20 and 30 cm long. The inner diameter of the distal section 132 of proximal segment 122 is between about 0.20 and O.S0 mm, more preferably between about 0.25 and 0.35 mm. The outer diameter of WO g4/18886 PCT/USg4102249 -7- ~ 120~ ~8 the distal section 132 of proximal segment 122 i9 between about 0.60 and 0.90 mm, more preferably between about 0.60 and 0.70 mm. The wall thicknes~ of the di~tal ~ection 134 of proximal ~egment 122 is between about 0.1 and 0.3 mm.
The tran~ition section 124 of the elongate tubular body 102 is less stiff than ~he proximal segment 122 but more stiff than the distal segment 120. A
suitable material that i8 biologically compatible i~ a polymer such as polyurethane, a block copolymer of polyamide, polyvinyl chloride or ~ilicone with greater durometer (i.e. that is stiffer) than the flexible distal segment 120. The transition section 124 may be radiopaque and thus ob~ervable in the event that the catheter becomes lodged in a particular portion of the vasculature or buckle~, and as such the polymeric material is doped with a radiopaque material such as barium sulfate, bismu~h subcarbo~ate, bismuth trioxide, tung~ten, tantalum or the like. The tran~ition section 124 makes up between about 10 and 20~ of the total length of the tubular member 102 and i8 between about 20 and 40 cm long, preferably between about 25 and 35 cm long. The transition section 124 may be of constant diameter or may be tapered. m e inner diameter of the transition section 2S 124 i8 between about 0.20 and 0.50 m~, ~ore preferably between abou~ 0.20 and 0.35 mm. The outer diameter of the transition section 124 i~ between about 0.50 and 0.90 mm, re preferably between about 0.60 and 0.70 mm. The wall thickness of the transition section 124 i9 between about 0.1 and 0.3 mm.
The proximal ~egment 122, transition ~ection 124 and di~tal ~egment 120 are joined at junctions 140 and 142, respectively. The junctionQ are formed by flaring, overlapping and heat fusing the materials of the proximal segment 122 and transition ~ection 124 and the WO g4/18886 PCTIUS94/02249 transition section 124 and distal segment 120. The distal segment 120, tranQition section 124 and distal ~ection 132 of proximal segment 122 may all have approximately the same out~ide diameter or the transition section 124 and the distal section 132 of the proximal ~egment-122 may be tapered.
A standard proximal end fitting 150 is attached to the proximal section 134 of the proximal segment 122 by heat fusion with reinforcing tubing.
FIG. 2 shows one embodiment of the distal segment 120 of the catheter wherein the tip 160 of the catheter is shaped with ~3team such that the diatal end 106 points to the wall of the ve~sel rather that straight into the path of blood flow for ease of manipulation through the tortuous vessel pathway. The particular embodiment shown i~ an "S" shape, but the tip may be any shape that allows for access to the particular vasculature being treated. In this way, if the catheter becomes lodged against the ves~3el wall, the infusion of liquid through the catheter propels the distal end 106 of the catheter away from the vessel wall. A~ the ~tiff proximal segment 122 is pushed, the distal segment 120 will be carried by the blt~od flood to the target site.
The catheter described above is useful in 2S delivering diagnostic, therapeutic, or vasoocclusive agent~ to deep tissue.
FIG. 3 shows a catheter as~embly 200 for placing the infusion catheter 100 at the target site~ An appropriate guiding catheter 202 i~ inserted into the 30 vasculature using standard placement techniques. A
rotating hemo~tatic valve 204 i~ connected to the guiding catheter luer adapter 206. The guiding catheter 202 is continuou~ly flushed with saline. The thumb-screw of the valve 204 is opened and the infusion catheter 100 is 35 inserted through the rotating hemostatic ~ralve 204.

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WO 94/1~886 PCT/IJS94/02249 21~ 9 :~CC3 Optionally, aq shown in FIG. 3, a teflon-coated stainless steel stylet 208 is first inserted into the infusion catheter 100 in order to prevent kinking of the infusion catheter 100 within the valve 204. The distal end 106 of the infusion catheter 100 iq advanced proximal to-the tip of the guiding catheter 202. The stylet 208 is then remo~ed from the infusion catheter 100. Once the stylet 208 is removed, the infusion catheter 100 is pu~hed out of the guiding catheter 202. The infusion catheter 100 is gently guided by the flow of blood in the ~asculature to the target site. Optionally, gentle pushing and pulling and injection of saline or contrast medium through the catheter lumen 108 may aid in the placement of the catheter at the target site.
FIG. 4 shows the method of inserting the infusion catheter into a tissue region which is reached by a tortuous path. The figure shows a region of ~oft tissue 300, such as in the region of the brain, containing a target site 302. Initially the guiding catheter, indicated at 202 is fed from a ~ascular access region~ The infusion catheter 100 i~ inserted into the guiding catheter 202 and then pushed out of the end of the guiding catheter. ~lood flow in the vessel then directs the infusion catheter 100 to the target site 302.
Once the infusion catheter i8 placed at the target si~e, a ~yringe may be connected to the proximal end fitting lSO and the diagnostic, therapeutic or ~asoocclusive agent may be infused through the catheter lumen 108 and into the target site. The injected agent may include radiopaque agents for viewing blood vessel anatomy and blood flow characteristics in the target region, vasoocclusi~e agents which can be u3ed to produce small-artery ~asoocclusion in the tis~ue region supplied by the target vessel, and pharmacological agents, such as anti-tumor drug3 or sclerosing agent~ ~uch as alcohols, W094/l~UK PCT~4/OZ~9 2 1 2 0 ~ 18 -lo-which are effective againct identified disease states at the target site. Vasoocclu~ive agents useful in the treatment of arteriovenou~ malformations include polymer~
that are activated in the pre~ence of polar solvent~ such 5 as water and include material~ ~uch as n-butylcyanoacrylate. Other types of vasoocclusive agent useful in the treatment of arteriovenous malformations include polymer solutions that coagulate by di~fusion of the solvent when in contact with blood. Polyvinyl 10 acetate dissolved in dimethylsulfoxide is one ~uch agent.
Alternatively, vasoocclusive coils 304 may be injected into the infusion catheter and delivered to a target site to occlude the blood flow at that site.
The following Examples are intended to 15 illustrate the invention but not to limit it in any manner.

Examples 20 Example 1 - Compari~on of Burst PressurQs - Prior art catheter~, in particular the "ZEPHYR~
catheter first marketed in 1991 were tested for burst pressure as were the inventive catheters. Pressure was applied by injecting liquid with pressures in the range 25 of O to burst in 25-30 psi increments into the proximal ,r end fitting of the catheter- The prior ~rt catheter s burst at the distal end when approximately 141 p~i of pressure was applied. This value was a mean value for - the catheters tested and therefore, statistically, 99.73%
30 (3 sigma) of the values for burst pressure for the prior '7' art catheters lie between about 97 and 185 psi- The catheter~ of the present invention burst at the distal end when a mean value of 207 pci of pressure was applied.
99.73S (3 sigma) of the values for burst pressure for the 35 inventive catheters, therefore, lie between about 195 and ,~,,.

-11- 2121)918 220 p8i; The inventive catheters, therefore proved to be ~tronger than the prior art catheters.

Example 2 - Testing of Distal End Flexibility The flexibilities of the distal ends of the prior art "ZEPHYR" catheter and the inventive catheters were compared using a Tinius Olsen bending stiffness tester. The results are graphically described in FIG. 5.
10 centimeter portions of the distal segments of each catheter were placed on the steel plate of the Olsen stiffnesq tester. The material was deflected to different positions and the corre~ponding pounds of force recorded. When the inventive catheter was deflected 10, the stiffness tester ~howed a force of 7xlO-5 pounds, when it was deflected 50 the force was 3.~x10-4 pounds, and when the deflection was 80, the force was 4.9x10-4 pounds. The prior art catheter was deflected 10 and the stiffness te~ter showed a force of 7.5x10-3 pounds, when it was deflected 50 the force wa~ 8.Sx10-2 pounds, and when the deflection was 80, the ~orce was 1.23xlO-1 pounds. The inventive catheter, therefore, proved to be much more flexible than the prior art catheter. Upon calculation of the slope of the lineq shown in FIG. S, for the inventive catheter, a 1 deflection corresponds t 25 to 10-5 pounds of force, and for a prior art catheter, a ~$ 0.3 deflection correspond~ to 10-5 pounds of force.
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While preferred e~bodiments of the i~vention ; have been described herein, it will be recognized that a 30 ~ariety of changes and modifications can be made without departing frcm the invention.

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Claims

Claims 1. A catheter that can be guided by the blood flow within a vessel, said catheter comprising an elongate tubular member having proximal and distal ends and an inner lumen extending between these ends, said member comprising:
(a) a relatively stiff tapered proximal segment;
(b) a relatively flexible and strong distal segment; and (c) a transition section between said proximal and said distal segments that is less flexible than the distal segment but more flexible than the proximal segment;
wherein said distal segment has a burst pressure of at least about 195 psi and is made of a material which will show a force of about 10-4 pounds or less when ten centimeters of the material is deflected 10° from horizontal.

2. The catheter of claim 1 wherein the burst pressure of the distal segment is between about 195 and 220 psi.

3. The catheter of claim 1 wherein the distal section is made of a material that further will show an additional force of about 10-5 pounds or less for each 1°
of deflection of the material from horizontal.

4. The catheter of claim 1 wherein the proximal segment is made of a polymeric material selected from the group consisting of nylon, polyvinyl chloride, polyethylene terephthalate or other polyester elastomer or of a polymer outer core with a metallic mesh inner core.

5. The catheter of claim 1 wherein the distal segment is made of a polymeric material selected from the group consisting of polyurethane, a block copolymer of polyamide, polyvinyl chloride, silicone and blends thereof.

6. The catheter of claim 5 wherein the polymeric material of the distal segment is doped with a metallic material selected from the group consisting of barium sulfate, bismuth trioxide, bismuth subcarbonate, tungsten and tantalum.

7. The catheter of claim 1 wherein the transition section is made of a polymeric material selected from the group consisting of polyurethane, a block copolymer of polyamide, polyvinyl chloride, and silicone.

8. The catheter of claim 7 wherein the polymeric material of the transition section is doped with a metallic material selected from the group consisting of barium sulfate, bismuth trioxide, bismuth subcarbonate, tungsten and tantalum.

9. The catheter of claim 1 wherein the distal segment is in an S-shaped configuration.

10. A method for accessing a target site, said method comprising:
(a) inserting a guiding catheter into the vasculature;
(b) inserting the infusion catheter of claim 1 into the guiding catheter; and (c) pushing the infusion catheter out of the guiding catheter into the vasculature such that the blood flow in the vessel directs the infusion catheter to the target site.

11. The method of claim 10 which further comprises inserting a stylet into the infusion catheter in order to insert the catheter into the guiding catheter and further removing the stylet prior to pushing the infusion catheter out of the guiding catheter and into the vasculature.

12. The method of claim 11 wherein the stylet is a teflon-coated stainless steel stylet.

13. A method for delivering a diagnostic, therapeutic or vasoocclusive agent to a target site within the vasculature, said method comprising:
(a) inserting a guiding catheter into the vasculature;
(b) inserting the infusion catheter of claim 1 into the guiding catheter;
(c) pushing the infusion catheter out of the guiding catheter into the vasculature such that the blood flow in the vasculature directs the infusion catheter to the target site; and (d) injecting the diagnostic, therapeutic or vasoocclusive agent through the catheter lumen and into the target site.

14. The method of claim 13 which further comprises inserting a stylet into the infusion catheter in order to insert the catheter into the guiding catheter and further removing the stylet prior to pushing the the vasculature.

15. The method of claim 13 wherein the vasoocclusive agent is n-butylcyanoacrylate and the target site is an arteriovenous malformation.

16. The method of claim 13 wherein the vasoocclusive agent is polyvinylacetate dissolved in dimethylsulfoxide and the target site is an arteriovenous malformation.

17. The method of claim 13 wherein the vasoocclusive agent is a vasoocclusive coil.

AMENDED CLAIMS
[received by the International Bureau on 21 July 1994 (21.07.94);
original claim 1 amended; remaining claims unchanged (1 page)]

1. A catheter that can be guided by the blood flow within a vessel, said catheter comprising an elongate tubular member having proximal and distal ends and an inner lumen extending between these ends, said member comprising:
(a) a tapered proximal segment that is between about 110 and 160 cm long and has a wall thickness of between about 0.1 and 0.4 mm, an outer diameter of between about 0.6 and 1.2 mm, and an inner diameter of between about 0.2 and 0.6 mm;
(b) a distal segment that is between about 5 and 40 cm long and has a wall thickness of between about 0.1 and 0.3 mm, an outer diameter of between about 0.5 and 0.8 mm, and an inner diameter of between about 0.25 and 0.5 mm; and (c) a transition section between said proximal and said distal segments that is between about 20 and 40 cm long and has a wall thickness of between about 0.1 and 0.3 mm, an outer diameter of between about 0.5 and 0.9 mm, and an inner diameter of between about 0.2 and 0.5 mm;
wherein said distal segment has a burst pressure of at least about 195 psi and is made of a material which will show a force of about 10-4 pounds or less when ten centimeters of the material is deflected 10° from horizontal.

2. The catheter of claim 1 wherein the burst pressure of the distal segment is between about 195 and 220 psi.

3. The catheter of claim 1 wherein the distal section is made of a material that further will show an