WO2022263299A1

WO2022263299A1 - Solution-based denaturing of chronic clot through a weeping balloon

Info

Publication number: WO2022263299A1
Application number: PCT/EP2022/065784
Authority: WO
Inventors: Ryan Michael SOTAK
Original assignee: Koninklijke Philips NV
Current assignee: Koninklijke Philips NV
Priority date: 2021-06-16
Filing date: 2022-06-10
Publication date: 2022-12-22
Anticipated expiration: 2023-12-16

Abstract

A balloon angioplasty device (10) includes a balloon angioplasty catheter (12) including a porous balloon (14); and an inflation device (20) comprising an acidic working fluid (16) and configured to inflate the porous balloon disposed inside a vascular obstruction using the acidic working fluid. The porous balloon has a porosity effective for the acidic working fluid to leak outside the inflated porous balloon disposed inside the vascular obstruction.

Description

SOLUTION-BASED DENATURING OF CHRONIC CLOT THROUGH A WEEPING

BALLOON

FIELD

[0001] The following relates generally to the catheter arts, catheter balloon arts, vascular therapy arts, percutaneous transluminal angioplasty (PTA) arts, and related arts.

BACKGROUND

[0002] Chronic venous disease or insufficiency is a condition in which clots form in the venous circulation system, especially in the lower extremities. In healthy patients, venous clots may resolve by action of natural lytics (which dissolve the fibrin comprising the young clot) being released into the circulation and normal activity. The longer a thrombus persists in the vein, the more difficult its removal becomes and the more likely that it will cause harm, especially if it develops into an embolus.

[0003] If a clot persists in a vein longer than about 30 days, it is reclassified as chronic clot because its composition has changed from primarily fibrinous to primarily crosslinked collagen, like a scar in the vein. Once developed, a chronic clot often will reduce venous blood flow to little or nothing causing significant symptoms. A chronic clot attaches to a vein wall via tendrils called synechiae, and is very rubbery, elastic, and tough.

[0004] Because of its physical properties, a chronic clot is difficult to remove or remodel to re-establish blood flow using conventional interventional techniques like angioplasty ballooning, debulking, and stenting. Attempts to stent a chronic clot often results in 1ST (in-stent thrombus) or re-occlusion. Conventional techniques like laser ablation are expensive and of uncertain effectiveness. Surgical removal of a chronic clot is a highly invasive procedure that can be damaging to surrounding tissues and still result in vessel scarring.

[0005] The following discloses certain improvements to overcome these problems and others.

SUMMARY

[0006] In some embodiments disclosed herein, a balloon angioplasty device includes a balloon angioplasty catheter including a porous balloon; and an inflation device comprising an acidic working fluid and configured to inflate the porous balloon disposed inside a vascular obstruction using the acidic working fluid. The porous balloon has a porosity effective for the acidic working fluid to leak outside the inflated porous balloon disposed inside the vascular obstruction.

[0007] In some embodiments disclosed herein, a balloon angioplasty method includes positioning, with a catheter, a porous balloon in a vascular obstruction; inflating the porous balloon to perform balloon angioplasty on the vascular obstruction using a working fluid; and leaking the working fluid out of the inflated porous balloon whereby the working fluid chemically softens the vascular obstruction.

[0008] In some embodiments disclosed herein, a balloon angioplasty device includes a balloon angioplasty catheter including a porous balloon; and an inflation device comprising an acidic working fluid and configured to inflate the porous balloon disposed inside a vascular obstruction using the acidic working fluid. The acidic working fluid is effective to soften collagen of a vascular obstruction within which the porous balloon is inflated. The porous balloon has a porosity effective for the acidic working fluid to leak outside the inflated porous balloon disposed inside the vascular obstruction.

[0009] One advantage resides in providing a percutaneous transluminal angioplasty (PTA) procedure that is effective for remodeling chronic clots.

[0010] Another advantage resides in providing a PTA therapy device that combines pressure applied by an inflated porous balloon and acidic fluid leaking from the porous balloon to remodel a clot by a combination of physical force and weaking of chemical bonds of crosslinked collagen of the clot.

[0011] Another advantage resides in providing a vascular therapy device to treat a chronic clot without damaging surrounding tissues.

[0012] Another advantage resides in providing PTA with chemical assistance by way of acidic fluid applied by a porous balloon that washes out to revert ambient blood to normal slightly basic pH after treatment with the acidic fluid, thereby quickly terminating the softening effect of the acidic solution and “setting” the collagen-rich clot in its remodeled shape.

[0013] A given embodiment may provide none, one, two, more, or all of the foregoing advantages, and/or may provide other advantages as will become apparent to one of ordinary skill in the art upon reading and understanding the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS [0014] The disclosure may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the disclosure. [0015] FIGURE 1 diagrammatically illustrates a balloon angioplasty device in accordance with the present disclosure.

[0016] FIGURE 2 diagrammatically illustrates a method of performing a balloon angioplasty method as disclosed herein using the device of FIGURE 1.

DETATEED DESCRIPTION

[0017] The following relates to percutaneous transluminal angioplasty (PTA), sometimes also referred to as balloon angioplasty. In PTA, a catheter with a deflated balloon is delivered along a guidewire to the clot. The balloon is then inflated, optionally using a fluid with a radiopaque contrast medium to enable observation of the balloon inflation in fluoroscopy imaging. The force of the inflated balloon remodels the clot by pressing it against the blood vessel wall so as to provide a larger opening for blood flow.

[0018] However, this procedure is often ineffective with chronic clots, in which the clot persists for around a month or longer and transforms to primarily crosslinked collagen, which is rubbery, elastic, and tough. PTA is generally ineffective at remodeling a collagen-rich clot to enlarge blood vessel lumen, because the tough crosslinked collagen resists deformation. Furthermore, to the extent that it does deform, the crosslinked collagen deforms elastically under the force of the expanded balloon, and then elastically reverts to (close to) its original shape after removal of the balloon force.

[0019] In some embodiments disclosed herein, the conventional balloon used in PTA is replaced with a weeping (i.e., porous) balloon, which is porous so as to allow leakage of the fluid used to inflate the weeping balloon into the vasculature. In one example, the weeping balloon is made of expanded Polytetrafluoroethylene (ePTFE) in which the expansion pressure introduces liquid flow through the pores in the ePTFE balloon. Alternatively, laser cutting or another approach can be used to provide a weeping balloon with suitable porosity for leaking out a portion of the inflation fluid.

[0020] In addition, the working fluid for inflating the weeping balloon is an acidic solution.

Normal venous blood has a slightly basic pH of typically around 7.3 -7.4. On the other hand, collagen in a slightly acidic pH solution softens and is more easily remodeled to enlarge the blood lumen.

[0021] Advantageously, the disclosed approach combines outward physical force provided by the weeping balloon with weakening of the chemical bonds of the collagen by the acidic solution applied to the collagen by the weeping balloon. The acidic solution is applied directly to the collagen-rich clot by way of the weeping balloon, thereby avoiding injecting a high concentration of the acidic solution into the bloodstream. Once the balloon is deflated, the weeping of the acidic solution ceases and blood flow quickly reverts the ambient blood to normal slightly basic pH, thereby quickly terminating the softening effect of the acidic solution and “setting” the collagen-rich clot in its remodeled shape providing an enlarged vessel lumen. Thus, the disclosed approach overcomes both the toughness of the collagen-rich clot by way of chemically weakening the chemical bonds of the collagen, and the elasticity of the collagen-rich clot by providing plastic (rather than elastic) deformation of the collagen and by removing the acidic solution simultaneously with the removal of the outward physical force to prevent the collagen from rebounding to its original shape.

[0022] As a further advantage, from an operator standpoint, no change in the usual PTA procedure is required other than using a catheter with a weeping balloon in place of a catheter with the usual angioplasty balloon and using a modified acidic working fluid at the desired pH, and possibly adjusting the inflation pressure and time to enhance effectiveness of the combined action of the pressure and the acidic solution.

[0023] In some embodiments disclosed herein, the acidic solution and its concentration, the inflation pressure, and the inflated balloon dwell time can be determined based on preclinical and/or clinical tests. For example, bovine or other animal vasculature having a clot or equivalent collagen-rich occlusion can be connected to a flow of blood or another fluid with similar pH (e.g., a saline solution), which can serve as a test platform for optimizing the inflation pressure, time, and acidic solution pH to remodel the occlusion. Additionally or alternatively, as the acidic solution used in a clinical PTA procedure can still contain radiopaque contrast agent, the operator may optionally directly observe effectiveness of the modified PTA procedure disclosed herein, for example by increasing dwell time by a small amount if the balloon is observed via fluoroscopic imaging to be continuing to expand at the end of the recommended dwell time. As another example, if the operator observes the PTA is not achieving the desired remodeled lumen size, the operator may optionally increase the pressure and/or increase the acidic pH of the working fluid to increase the efficacy of the PTA procedure in real time.

[0024] In some embodiments disclosed herein, after the dwell time is complete, the balloon is deflated and then reinflated with a basic solution such as saline to more quickly “set” the remodeled collagen-rich clot. However, it is generally expected that the natural flow of blood with its slightly basic pH will set the remodeled clot with sufficient rapidity.

[0025] The disclosed device can be implemented in the venous system, both in the peripheral venous system and in main vein vessels, but is also applicable for arterial clots as well. [0026] With reference to FIGURE 1, an illustrative balloon angioplasty (i.e., PTA) device

10 is diagrammatically shown. As shown in FIGURE 1, the device 10 is disposed adjacent an obstruction O within a blood vessel V of a patient. Typically (although not-necessarily) the obstruction O is a clot, such as a chronic clot that is rich in crosslinked collagen. The device 10 includes a balloon angioplasty catheter 12 with a porous balloon 14 attached to an end thereof adjacent or near the obstruction O. An inflation device 20 is configured to inflate the porous balloon 14 disposed inside the vascular obstruction O. The inflation device 20 comprises an acidic working fluid 16 and a pump or other mechanism to deliver the acidic working fluid 16 at a pressure sufficient to overcome the ambient blood pressure in the blood vessel V in order to inflate the porous balloon 14 and apply outward mechanical pressure against the obstruction O.

[0027] The porous balloon 14 has a porosity effective for a leaked portion 16L of the acidic working fluid 16 to leak outside the inflated porous balloon 14 when the porous balloon 14 is disposed inside the vascular obstruction O and inflated with the working fluid 16. In some embodiments, the porous balloon 14 comprises expanded Polytetrafluoroethylene (ePTFE) which has some porosity created during the manufacturing process. In other embodiments, the porous balloon 14 has pores or openings 18 comprising laser-cut openings in the porous balloon 14. The pressure on the porous balloon 14 is used to allow the acidic working fluid 16 to overcome surface tension on the ePTFE surface of the porous balloon 14 and allow transport of the acidic working fluid 16 through the pores 18. These are merely illustrative examples of porous balloons suitable for use as the porous balloon 14.

[0028] The acidic working fluid 16 is effective to soften collagen of the vascular obstruction O within which the porous balloon 14 is inflated. In some nonlimiting illustrative embodiments, the acidic working fluid is an aqueous solution of an acid that has an acidic pH of less than 7 0 In some nonlimiting illustrative embodiments, the acidic working fluid 16 has a pH value of 6.0 or less. In a particular example, the acidic working fluid 16 could comprise an aqueous solution of Phosphoric, Citric, Acetic, Histidine Lactic, Tromethamine Gluconic, Aspartic, Glutamic, Tartanic, Succinic, Malic, Fumaric acids, or similar acidic solutions compatible with the vascular system. The acidic working fluid 14 delivers hydrogen ions (H⁺) to the obstruction O by the following reaction:

2H2O 0₂ + 4H⁺ + 4e .

[0029] Collagen is known to soften and even eventually dissolve in the presence of acid

(more particularly, in the presence of H⁺ ions) by breaking ionic crosslinks.

[0030] In some embodiments, the acidic working fluid 16 further includes a radiopaque contrast medium, thereby allowing visualization of the porous balloon 14 under fluoroscopic imaging. The acidic working fluid 16 is delivered by an inflation source 20 connected to the porous balloon 14 via a tube 22 feeding into the catheter 12.

[0031] With further reference to FIGURE 2 and continuing reference to FIGURE 1,

FIGURE 2 shows an illustrative embodiment of a balloon angioplasty (i.e., PTA) method 100 diagrammatically shown as a flowchart. At an operation 102, the catheter 12 with the porous balloon 14 at its distal end is inserted into a blood vessel and fed to the illustrative vessel V so that the porous balloon 14 is positioned in the vascular obstruction O. The operation 102 may use any suitable catheter insertion approach, such as initially inserting a guidewire (not shown) and then running the catheter 12 along the guidewire. The insertion process 102 is preferably monitored by real-time fluoroscopic imaging (for example, using a C-arm imaging device, CT scanner, fluoroscope, or other fluoroscopic imaging device, not shown), at least in the region around the obstruction O. At an operation 104, the porous balloon 14 is inflated with the working fluid 16 to perform balloon angioplasty on the vascular obstruction O. The inflation of the porous balloon 14 causes the porous balloon 14 to be pressed against the obstruction O, thereby providing treatment of the obstruction O by outward mechanical pressure. Simultaneously, at an operation 106, the working fluid 16 leaks out of the inflated porous balloon 14 soften the vascular obstruction O. That is, the working fluid leakage 106 occurs inherently due to the pressurization of the porous balloon 14 in operation 104, due to the porosity of the porous balloon 14.

[0032] In an operation 108, the inflation of the porous balloon 14 is maintained at a therapeutically effective pressure for a therapeutically effective time interval. The pressure and time may be predetermined based on preclinical and/or clinical studies, and may in some embodiments be programmed into the inflation device 20 if it is computerized. Optionally, the operator may adjust the pressure and/or increase the time of the operation 108 based on observations made via real-time fluoroscopic imaging. For example, if the inflated balloon size observed via fluoroscopy and a contrast medium component of the working fluid 16 indicates to the operator that the pressure is insufficient to achieve a desired remodeling of the obstruction O, then the operator may adjust a control of the inflation device 20 to increase the pressure. Additionally or alternatively, the operator may increase the acidity of the acidic solution if this is a controllable parameter. For example, if the inflation device 20 forms the working fluid 16 in real-time by mixing a flow of a strong(er) acid and a flow of diluting aqueous solution, then the acidity can be increased by increasing the acid-to-aqueous solution ratio. As another contemplated adjustment, if the programmed inflation time is reached but the operator observes that the balloon is continuing to expand in size (indicating the obstruction O is continuing to be remodeled) then the operator may extend the time until the balloon stops expanding or reaches a target size.

[0033] In an operation 110 performed at the end of the operation 108, the porous balloon

14 is deflated by removing the application of pressurized working fluid by the inflation device 20. This will automatically result in simultaneous cessation of the working fluid leakage 16L that was driven by the pressure in the balloon 14. Blood flow through the blood vessel V then quickly washes the working fluid away from the vicinity of the obstruction O, thus quickly stopping the chemical softening of the collagen bonds and setting the remodeled obstruction. While natural blood flow is generally expected to be sufficient to provide this rapid setting effect, at an optional operation 112, the balloon after deflation via operation 110 may be re-inflated, but this time using a saline fluid (e.g., from the inflation source 20) or some other basic solution. The saline then leaks into the obstruction O. The saline allows the remodeled collagen-rich clot to “settle” more quickly.

[0034] The disclosure has been described with reference to the preferred embodiments.

Modifications and alterations may occur to others upon reading and understanding the preceding detailed description. It is intended that the exemplary embodiment be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims

CLAIMS:

1. A balloon angioplasty device (10), comprising: a balloon angioplasty catheter (12) including a porous balloon (14); and an inflation device (20) comprising an acidic working fluid (16) and configured to inflate the porous balloon disposed inside a vascular obstruction using the acidic working fluid; wherein the porous balloon has a porosity effective for the acidic working fluid to leak outside the inflated porous balloon disposed inside the vascular obstruction.

2. The device (10) of claim 1, wherein the porous balloon (14) comprises expanded Polytetrafluoroethylene (ePTFE).

3. The device (10) of claim 1, wherein the porous balloon (14) has pores (18) comprising laser-cut openings in the porous balloon.

4. The device (10) of any one of claims 1-3, wherein the acidic working fluid (16) is effective to soften collagen of a vascular obstruction within which the porous balloon (14) is inflated.

5. The device (10) of claim 4, wherein the acidic working fluid (16) has a pH value of 6.0 or less.

6. The device (10) of either one of claims 4 and 5, wherein the acidic working fluid (16) comprises an aqueous solution of Phosphoric, Citric, Acetic, Histidine Lactic, Tromethamine Gluconic, Aspartic, Glutamic, Tartanic, Succinic, Malic, or a Fumaric acid.

7. The device (10) of any one of claims 1-6, wherein the acidic working fluid (16) comprises a radiopaque contrast medium.

8. A balloon angioplasty method (100), comprising: positioning, with a catheter (12), a porous balloon (14) in a vascular obstruction; inflating the porous balloon to perform balloon angioplasty on the vascular obstruction using a working fluid (16); and leaking the working fluid out of the inflated porous balloon whereby the working fluid chemically softens the vascular obstruction.

9. The method (100) of claim 8, wherein the working fluid (16) is an acidic working fluid.

10. The method (100) of claim 8, wherein the working fluid (16) has a pH of at least 6.0 or less.

11. The method (100) of any one of claims 8-10, wherein the working fluid (16) comprises a radiopaque contrast medium, and the method further comprises: monitoring the balloon angioplasty using fluoroscopic imaging.

12. The method (100) of claim 11, further comprising: deflating the porous balloon (14) in response to the inflated porous balloon ceasing to expand as observed by the fluoroscopic imaging.

13. The method (100) of any one of claims 8-12, further including: after the leaking, filling the porous balloon (14) with a saline solution; and controlling the pressure of the porous balloon to allow leakage of the saline therefrom.

14. The method (100) of any one of claims 8-13, further including: before the positioning, forming one or more openings (18) in the porous balloon (14) to allow leakage of the fluid (16) therefrom.

15. A balloon angioplasty device (10), comprising: a balloon angioplasty catheter (12) including a porous balloon (14); and an inflation device (20) comprising an acidic working fluid (16) and configured to inflate the porous balloon disposed inside a vascular obstruction using the acidic working fluid, the acidic working fluid being effective to soften collagen of a vascular obstruction within which the porous balloon is inflated; wherein the porous balloon has a porosity effective for the acidic working fluid to leak outside the inflated porous balloon disposed inside the vascular obstruction.

16. The device (10) of claim 15, wherein the porous balloon (14) comprises expanded Polytetrafluoroethylene (ePTFE).

17. The device (10) of claim 15, wherein the porous balloon (14) has pores (18) comprising laser-cut openings in the porous balloon.

18. The device (10) of any one of claims 15-17, wherein the acidic working fluid (16) has a pH value of 6.0 or less.

19. The device (10) of claim 18, wherein the acidic working fluid (16) comprises an aqueous solution of Phosphoric, Citric, Acetic, Histidine Lactic, Tromethamine Gluconic, Aspartic, Glutamic, Tartanic, Succinic, Malic, or a Fumaric acid.

20. The device (10) of any one of claims 15-19, wherein the acidic working fluid (16) comprises a radiopaque contrast medium.