阅读说明：本技术 循环扩张组织治疗程序及相关联的系统 (Cyclic dilated tissue treatment procedures and associated systems ) 是由 M·J·伯德诺 M·A·舒米德尔 E·E·肖 B·C·肖特 A·玛莎 M·B·德纳多 F 于 2019-09-26 设计创作，主要内容包括：本公开总体涉及利用扩张元件的治疗程序,比如与闭塞和治疗剂递送设备、系统和方法相关联的那些扩张元件。在一些更具体的示例中,治疗程序包括在预选频率分布下的扩张-收缩循环,该频率分布构造成为治疗特定状况,比如动脉导管的钙化。(The present disclosure relates generally to therapeutic procedures utilizing expansion elements, such as those associated with occlusion and therapeutic agent delivery devices, systems, and methods. In some more specific examples, the treatment procedure includes a dilation-constriction cycle at a preselected frequency profile configured to treat a particular condition, such as calcification of an arterial duct.)

1. A method of treating a blood vessel having a nominal (starting) diameter at a treatment site within a mammalian body, the method comprising:

providing a device comprising a stent element mounted on a catheter, the stent element configured to expand and contract at a first frequency of 0.1 to 10 Hz;

orienting the expansion element at the treatment site; and

cycling the expansion element at the treatment site at the first frequency between a first diameter that is greater than the nominal (starting) diameter and a second diameter that is less than the first diameter;

thereby, the nominal (starting) diameter of the treatment site is increased after the treatment and the removal of the expansion element.

2. The method of claim 1, wherein the expandable element is a drug-coated balloon, wherein the result of circulating the drug-coated balloon comprises increasing the efficacy of drug delivery to the treatment site.

3. The method of any of the preceding claims, wherein the expansion element cycles according to a frequency configured to treat the treatment site.

4. The method of any of the preceding claims, wherein the expansion element is cycled according to a treatment procedure, wherein the treatment procedure comprises a varying strain rate, strain percentage, number of cycles, expansion amplitude, expansion frequency, change in expansion element volume, change in expansion element pressure, or change in expansion element diameter.

5. The method of any of the preceding claims, wherein the expansion element has a compliance configured to treat a desired vessel diameter.

6. The method of any of the preceding claims, wherein the expansion element is configured to radially expand in the absence of a localized shear load on the vessel.

7. The method of any of the preceding claims, wherein the expansion element is longitudinally flexible.

8. The method of any of the preceding claims, wherein the expansion element comprises a drug coating, a scoring element, a cutting element, a topographical feature, or a stent attached to a balloon.

9. The method of any of the preceding claims, wherein the expansion element is cycled at the first frequency using a pressurized source.

10. A method of treating a tissue site within a patient, the tissue site having a nominal size, the method comprising:

delivering one or more expansion elements of a medical device to the tissue site, the medical device configured to expand and contract the one or more expansion elements;

operating the medical device according to a treatment procedure such that the one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expanding and contracting between a first size and a second size larger than the first size by an increasing cyclic expansion curve, the increasing cyclic expansion curve comprising increasing values of the second size from an initial value larger than the nominal size and subsequent values larger than the initial value; and

removing the one or more dilation elements from the tissue site, thereby increasing the nominal size of the tissue site after removal of the one or more dilation elements.

11. The method of claim 10, wherein the one or more expansion elements comprise an endoluminal balloon.

12. The method of claim 10 or 11, wherein the tissue site is one of a blood vessel, a heart valve, or a respiratory conduit.

13. The method of any one of claims 10 to 12, wherein the treatment frequency is varied during the treatment procedure.

14. The method of any one of claims 10 to 12, wherein the treatment frequency is constant during the treatment procedure.

15. The method of any of claims 10-14, wherein the treatment procedure is performed using a single expansion element.

16. The method of any one of claims 10-14, wherein the treatment procedure is performed using a plurality of expansion elements, the method further comprising performing a first portion of the treatment procedure using a first expansion element of the plurality of expansion elements and performing a second portion of the treatment procedure using a second expansion element of the plurality of expansion elements, the first expansion element having a first nominal expansion size and the second expansion element having a second nominal expansion size.

17. The method of any one of claims 10 to 16, wherein the treatment procedure comprises changing a characteristic of the one or more expansion elements during the treatment procedure, the characteristic comprising a volume, a pressure, or a diameter of the one or more expansion elements.

18. The method of any of claims 10-17, wherein the treatment procedure is configured to be performed and the method is associated with a medical procedure comprising sinus rhinoplasty, kyphoplasty, rhinoplasty, or skin dilation.

19. The method of any one of claims 10 to 18, wherein the one or more expansion elements comprise a compliant balloon.

20. The method of any one of claims 10 to 19, wherein the one or more expansion elements comprise a non-compliant balloon.

21. The method of any of claims 10-20, wherein the medical device is coupled to a pressure modulator, the pressure modulator includes a power source connected to a pressurization source and a controller for controlling the pressurization source, the pressurization source is coupled with the one or more expansion elements to pressurize and depressurize the one or more expansion elements, and the controller includes a processor for causing the pressurization source to operate the one or more expansion elements according to the treatment procedure.

22. The method of claim 21, wherein the power source, the pressurized source, and the controller are held in a housing.

23. The method of claim 22, wherein the housing is configured to be retained in a hand of a user.

24. The method of any of claims 10 to 23, wherein the pressure modulator comprises a pressurized source comprising a piston driver, a screw driver, an air compressor, an air reservoir, a servo motor, a piezoelectric motor, or a pressurized reservoir.

25. The method of any of claims 10-24, wherein the expansion element comprises a scoring feature, a drug coating, a cutting feature, a controlled topography feature, or an off-axis expansion feature.

FIELD

The present disclosure relates generally to therapeutic procedures utilizing expansion elements, such as those associated with occlusion and therapeutic agent delivery devices, systems, and methods. In some more specific examples, the present disclosure provides a dilation-constriction cycle at a preselected frequency profile configured to treat a particular condition, such as calcification of an arterial duct.

Background

Intervention with a dilating element engaged with tissue at a treatment site may be beneficial for a variety of diseases and physiological disorders or conditions. Vascular diseases such as arteriosclerosis, arterial occlusion, preventive intervention of blood vessels, phlebitis, intimal hyperplasia, plaque, vessel dissection, peripheral arterial disease, aneurysm disease, stenosis, restenosis and skin dilation are just some examples of diseases/treatments that may benefit from intervention, including the use of an expansion element such as a catheter balloon to actively engage tissue. Improvements in tissue response, including vascular elastic response, associated with such treatments have yet to be realized.

International publication No. WO 2017/168145 relates to a medical device for assisting in the division, destruction or disintegration of calcified or otherwise hardened material within blood vessels of the human or animal body which otherwise prevents or inhibits stent placement procedures or passage of guidewires, catheters and other devices through the blood vessels. The apparatus includes a catheter having a lumen extending between a distal end and a proximal end of the catheter and a displaceable element at the distal end of the catheter configured to be displaced axially and/or radially relative to the catheter when driven by pressure fluctuations within the lumen. A pressure pump is coupled to the proximal end of the catheter and is configured to apply a baseline pressure to the catheter lumen. A pressure modulation source is also coupled to the proximal end of the catheter, the pressure modulation source being configured to modulate a baseline pressure in the lumen of the catheter with one or more pressure pulses, and preferably with a series of pressure pulses.

International publication No. WO 2016/134225 relates to a system and method relating generally to rotational atherectomy. More particularly, a method for methodically softening and otherwise disrupting calcifications located within atherosclerotic plaques, lesions or occlusions and/or within the walls of biological conduits or lumens. Softening and/or breaking of calcification in the exemplary artery wall is accomplished in conjunction with abrading to remove any occlusions located on the inner surface of the exemplary artery and thus within the lumen of the artery. This result is achieved by using at least one eccentric head that during high speed rotation within an exemplary lumen is found to produce a combination of low frequency orbital motion and/or high frequency beat frequency, the low frequency orbital motion comprising a force applied against the lumen wall, accompanied by the same deflection and/or high frequency beat frequency, also accompanied by a force applied on the lumen wall and the same deflection.

Us patent 4,439,186 relates to an expansion device for dilating or occluding blood vessels and other body lumens using a catheter having a dilating element. The expansion element is a balloon-type expansion element having a non-linear pressure-volume relationship. A pressure source is provided which supplies a pulsating pressure to the expansion element to cause the element to alternately expand and contract.

EP 0774163 relates to a stent expansion system comprising a balloon catheter, a portion of the tubular shaft of which is sequentially squeezed between a plunger reciprocating in a box and a saddle provided in a cover tightly fitted on the box. The pressurized fluid medium supplied to the bladder is pulsed by the squeezing and releasing action provided by the plunger and saddle.

Improvements in tissue response to dilation therapy remain to be realized. It is believed that none of the above approaches effectively address the preselected cyclic treatment process, including simulating or otherwise utilizing complex elastic material (e.g., stress relaxation) responses, such as those due to the Marlins effect, which is a particular aspect of mechanical response in filled rubber.

SUMMARY

Various inventive aspects described herein relate to systems, methods, and associated expandable intraluminal devices (e.g., balloons) for achieving improved tissue response to augmentation or other tissue expansion procedures. For example, the present disclosure provides concepts relating to periodic strain curves for use with expandable intraluminal devices to achieve improved histological response. Although the primary example is provided in the context of vascular therapy (e.g., balloon catheter manipulation on calcified vessels), it should be understood that the term "intraluminal" and applicability of the described methods and related systems apply to a variety of situations, including, but not limited to, the following therapies: peripheral arterial disease, arteriovenous fistula, venous disease, kyphoplasty, sinus thickening, skin dilation, valve disease (e.g., calcification), or others.

In certain examples, the systems and methods referenced above utilize concepts associated with the Marins effect that describe the type of hysteresis applicable to complex rubber materials, where the strain curve for a particular material depends on the maximum load previously encountered by that material. The various inventive concepts of the present disclosure utilize the theory that mechanisms similar to the marins effect translate into certain types of tissue, including diseased tissue, which can be utilized to achieve tissue softening/relaxation by the presence of residual strain/elongation that serves to break up, destroy or disintegrate calcified or other hardened substances in blood vessels within a human or animal body following an expansion cycle and/or enhanced treatment.

A first example ("example 1") relates to a method of treating a blood vessel having a nominal (starting) diameter at a treatment site within a mammalian body, wherein the method comprises providing a device comprising a stent element mounted on a catheter, the stent element configured to expand and contract at a first frequency of 0.1 to 10 Hz. The method also includes orienting the expansion element at the treatment site and cycling the expansion element at the treatment site at a first frequency between a first diameter that is greater than the nominal (starting diameter) and a second diameter that is less than the first diameter. According to the method, after treatment and removal of the expansion element, the nominal (starting) diameter of the treatment site is increased.

According to another still further example ("example 2") with respect to example 1, the expansion element is a drug-coated capsule, and one or more of the following occurs as a result of the treatment: increased drug absorption at the treatment site, reduced drug loss at the treatment site, reduced total amount of drug required for treatment at the treatment site, increased drug transfer efficiency of drug-coated capsules at the treatment site, and/or reduced drug wash-off from the treatment site.

According to yet another example ("example 3") further to any of the preceding examples, the expansion element is cycled according to a frequency configured to treat any one or more of: specific vessels, vascular disease states in the below-knee vessels, vascular disease states in the above-knee vessels, arterial venous circuits, coronary vessels, medial and/or endoluminal calcification lesions and/or vessels, venous valvular disease, kyphoplasty and fistula maturation (AV circuit).

According to yet another example ("example 4") further to any of the preceding examples, the expansion element cycles according to a treatment procedure in which one or more of: strain rate, percent strain, number of cycles, amplitude of expansion, frequency of expansion, change in volume of the expansion element, change in pressure of the expansion element, and change in diameter of the expansion element.

According to yet another example ("example 5") further to any of the preceding examples, the expansion element has a compliance configured to treat a desired vessel diameter.

According to yet another example ("example 6") which is further to any of the preceding examples, the expansion element is configured to radially expand in the absence of a local shear load on the vessel.

According to yet another example ("example 7") further to any of the preceding examples, the expansion element is longitudinally flexible.

According to yet another example ("example 8") further to any of the preceding examples, the expansion element includes any one or more of the following features: drug coating, scoring elements, cutting elements, topographical features, and stents attached to the balloon.

According to yet another example ("example 9") further to any of the preceding examples, the expansion element is cycled at the first frequency using one or more of: a hand-held battery-powered catheter system, squeeze bulb, piston pump, screw drive, and air modulator.

Another example ("example 10") relates to a method of treating a tissue site in a patient, the tissue site having a nominal size, the method comprising delivering one or more expansion elements of a medical device to the tissue site, the medical device configured to expand and contract the one or more expansion elements. The method also includes operating the medical device according to the treatment procedure such that the one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expanding and contracting between a first size and a second size larger than the first size via a gradual cyclical expansion curve that includes values of the second size increasing from an initial value larger than a nominal size and subsequent values larger than the initial value. The method further includes removing the one or more dilation elements from the tissue site, thereby increasing a nominal size of the tissue site after removing the one or more dilation elements.

According to yet another example ("example 11") which is further relative to example 10, the one or more expansion elements comprise an endoluminal balloon.

According to another further example ("example 12") with respect to any one of examples 10 or 11, wherein the tissue site is one of a blood vessel, a heart valve, or a respiratory tract.

According to yet another example ("example 13") with respect to any of examples 10 to 12, the treatment frequency varies during the treatment procedure.

According to yet another example ("example 14") with respect to any one of examples 10 to 12, the treatment frequency is constant during the treatment procedure.

According to yet another example ("example 15") further to any of examples 10 to 14, the treatment procedure is performed using a single dilation element.

According to yet another example ("example 16") further to any of examples 10 to 14, the treatment procedure is performed using a plurality of expansion elements, the method further comprising performing a first portion of the treatment procedure using a first expansion element of the plurality of expansion elements, the first expansion element having a first nominal expansion dimension, and performing a second portion of the treatment procedure using a second expansion element of the plurality of expansion elements, the second expansion element having a second nominal expansion dimension.

According to yet another example ("example 17") further to any of examples 10 to 16, the treatment procedure includes changing one or more of a volume, a pressure, and a diameter of the one or more expansion elements during the treatment procedure.

According to yet another example ("example 18") further to any of examples 10 to 17, the treatment procedure is configured to be performed, and the method is associated with one of a sinus rhinoplasty, a kyphoplasty, a rhinoplasty, or a skin dilation.

According to yet another example ("example 19") further to any of examples 10 to 18, the one or more expansion elements comprise a compliant balloon.

According to yet another example ("example 20") further to any of examples 10 to 19, wherein the one or more expansion elements comprise a non-compliant balloon.

According to yet another example ("example 21") which is further relative to any of examples 10-20, the medical device is coupled to a pressure modulator, the pressure modulator including a power source connected to a pressurization source and a controller for controlling the pressurization source, the pressurization source coupled with the one or more expansion elements to pressurize and depressurize the one or more expansion elements, and the controller including a processor for causing the pressurization source to operate the one or more expansion elements according to a treatment procedure.

According to yet another example ("example 22") that is further relative to example 21, the power source, the pressurization source, and the controller are held in a housing.

According to yet another example, which is further relative to example 22, the housing is configured to be retained in a hand of a user.

According to yet another example ("example 24") further to any of examples 10 to 23, the pressure modulator includes a pressurization source including one or more of a piston driver, a screw driver, an air compressor, an air reservoir, a servo motor, a piezoelectric motor, and/or a pressurization reservoir.

According to yet another example ("example 25") with respect to any of examples 10-24, the expansion element includes one or more of a scoring feature, a drug coating, a cutting feature, a controlled topography feature, and/or an off-axis expansion feature.

The foregoing examples are merely examples and are not to be construed as limiting or otherwise narrowing the scope of any inventive concept that is otherwise provided by the present disclosure. While multiple examples are disclosed, still other examples will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative examples of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive in nature.

Drawings

The accompanying drawings are included to provide a further understanding of the disclosure, are incorporated in and constitute a part of this specification, illustrate embodiments, and together with the description serve to explain the principles of the disclosure.

Fig. 1 illustrates a system for treating a tissue site within a patient according to some examples.

Fig. 2 illustrates a medical device of the system of fig. 1 for treating tissue within a patient according to some examples.

Fig. 3 illustrates a dilation element of a medical device of the system of fig. 1, according to some examples.

Fig. 4 illustrates a dilation element of a medical device of the system of fig. 1, according to some examples.

Fig. 5A-5C illustrate a testing device of the system according to fig. 1, according to some examples.

Fig. 6-11 illustrate various treatment procedures or portions thereof according to some examples.

Those skilled in the art will readily appreciate that the various aspects of the disclosure may be implemented by any number of methods and apparatuses configured to perform the intended functions. It should also be noted that the drawings referred to herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of the disclosure, and in this regard, the drawings should not be construed as limiting.

Detailed Description

Some inventive concepts provided by the present disclosure relate to a predetermined, periodic (e.g., low frequency) dilation-constriction therapy procedure and associated system for tissue treatment. In some examples, such treatment procedures and related systems include catheter-based balloon treatment of calcified plaque, which utilizes concepts similar to the marlins effect exhibited in filled rubber materials. The inventors have demonstrated the basis of these theories using methods such as Finite Element Model (FEM) analysis and cadaver vascular response testing, which indicate that such treatment procedures may result in more efficient pressure transfer to diseased tissue (e.g., calcified areas) and improved therapeutic ability through tissue softening/relaxation responses. Such stress transfer may, for example, help to enhance treatment to break up, destroy or disintegrate calcified or otherwise hardened material within a blood vessel of a human or animal body, or to provide other treatment as desired.

This disclosure is not intended to be read in a limiting sense. For example, terms used in the present application should be read broadly in the context that those skilled in the art should ascribe the meaning of such terms.

With respect to imprecise terms, the terms "about" and "approximately" are used interchangeably to refer to measured values that include the stated measured value and also include any measured value that is reasonably close to the stated measured value. As understood and readily determined by one of ordinary skill in the relevant art, measurements that are reasonably close to the measurement deviate from the measurement by a relatively small amount. For example, such deviations may be due to measurement errors or fine adjustments made to optimize performance. The terms "about" and "approximately" can be understood to be +/-10% of the stated value if it is determined that such reasonably minor differences would not be readily ascertainable by one of ordinary skill in the relevant art.

Examples of Automation systems

Fig. 1 illustrates a system 1000 for treating a tissue site within a patient according to some examples. As shown in fig. 1, the system 1000 includes a medical device 1100 and a pressure modulator 1102 connected to the medical device 1100. As shown, the pressure modulator 1102 includes a pressurization source 1104, a controller 1106, and a power source 1108. In some examples, the pressure modulator 1102 is automated or partially automated, and the power source 1108 is electrical (e.g., a battery), the controller 1106 is electronic (e.g., a microprocessor-based system), and the pressurized source 1108 is actuated by the controller 1106 according to the therapy program 1110. As shown in fig. 1, the medical device 1100 is transitionable between a collapsed state and an expanded state or size. In some examples, the pressure modulator 1102, or a portion thereof, is housed in a hand-held housing unit. In other examples, the pressure modulator 1102, or portions thereof, is suitably held by a suitable portable or stationary housing (see, e.g., fig. 5A and 5B).

Some methods of treating a blood vessel having a nominal (starting) diameter at a treatment site within a mammalian body include providing a device as described above (e.g., a device including a dilation element), such as medical apparatus 1100, mounted on a catheter. The expansion member is configured to expand and contract at a first frequency (e.g., 0.1 to 10Hz) according to a treatment procedure. In some examples, the expansion element is oriented at the treatment site and cycled at a first frequency to a first diameter that is greater than a nominal (starting) diameter of the treatment site and then to a second diameter that is less than the first diameter (e.g., greater than, equal to, or less than the nominal (starting) diameter of the treatment site). In this manner, the nominal (starting) diameter of the treatment site is increased after the treatment procedure and removal of the expansion element.

In some examples, a method of treating a tissue site (e.g., a blood vessel) having a nominal size within a patient includes delivering one or more expansion elements of a medical device 1100 to the tissue site, the medical device 1100 configured to expand and contract the one or more expansion elements. The medical device 1100 is operated according to a treatment procedure such that the one or more expansion elements expand and contract between a first size and a second size (greater than the first size) through a gradual cyclical expansion curve at a treatment frequency having a desired value (e.g., from 0.1Hz to 10 Hz). In some examples, the cyclic expansion procedure includes increasing a value of the second dimension of the one or more expansion elements from an initial value that is greater than a nominal dimension of the tissue site and a subsequent value that is greater than the initial value. In some methods, the one or more dilation elements are removed from the tissue site, thereby increasing a nominal size of the tissue site after the one or more dilation elements are removed.

Examples of Manual systems/operations

In various examples, a user (not shown) actuates one or more medical devices and/or pressure regulation systems according to a treatment procedure using manual techniques (e.g., via a manual pressurization system). As a non-limiting example, a physician may choose to manually operate a syringe or other pressurizing system to selectively cycle one or more expansion elements at a desired frequency according to the treatment procedures described herein.

Examples of medical device features

Fig. 2 illustrates a medical device 1100 for treating tissue within a patient according to some examples. As shown, the medical device 1100 includes a dilation member 10 and a catheter 15. In various embodiments, the catheter 15 has a cylindrical form and includes a longitudinal axis 17, a proximal end 18, a distal end 19, and a cover lumen 32 that optionally extends from the proximal end 18 to the distal end 19. The expansion element 10 includes an expandable member or expandable member 20 positioned on the distal section 16 of the catheter 15. As shown, expandable member 20 includes: a body section 21, which may be substantially cylindrical along a working length (W); two opposing legs 22; and a shoulder/tapered portion 23 which may be integrally connected to the body section 21 and the two opposing leg portions 22. Body section 21, legs 22 and shoulder/tapered portion 23 define the overall length of expandable member 20 from proximal end 24 to distal end 25.

Medical device 1100 has a first segment S1 that extends from distal end 19 of catheter 15 to proximal end 24 of expandable member 20, S1. Medical device 1100 also has a second section S2 that extends from proximal end 24 of expandable member 20 to proximal end 18 of catheter 15 at second section S2. The medical device 1100 also has a third section S3 corresponding to the length of the catheter 15, the third section S3 extending within the cover lumen 32 of the catheter 15 from the distal end 19 of the catheter 15 to the proximal end 18 of the catheter 15.

Examples of expansion element features

In some embodiments, expandable member 20 of expansion element 10 comprises a thermoplastic polymer material comprising polyurethane, PET, PEBAX, Polytetrafluoroethylene (PTFE), polyamides such as nylon 12, nylon 11, nylon 9, nylon 6/9, nylon 6/6, and combinations thereof.

The expandable member 20 of the expansion element 10 may comprise, for example, a non-compliant, substantially inelastic balloon. In such examples, expandable member 20 may comprise a material such as nylon, polyethylene terephthalate (PET), polycaprolactam, polyester, polyether, polyamide, polyurethane, polyimide, ABS copolymer, polyester/polyether block copolymer, ionomer resin, liquid crystal polymer, and rigid rod polymer configured to allow expandable member 20 to expand to a selected diameter when sufficiently pressurized and remain at or near the selected diameter under further pressurization until burst pressure is reached.

In some examples, expandable member 20 may include a compliant, relatively elastic balloon. In such examples, expandable member 20 may comprise materials such as, for example, polyurethane, latex, and elastomeric organosiloxane polymers such as silicone, configured to allow expandable member 20 to continuously increase in diameter as pressure on the balloon increases. The compliant, relatively elastic expandable member 20 may be preferred for deployment around bends such as within a patient's vasculature, as the more elastic expandable member 20 may mitigate undesirable straightening forces during deployment. However, a compliant, relatively elastic expandable member 20 may be more susceptible to uneven deployment than a non-compliant, generally inelastic expandable member 20.

In still other examples, expandable member 20 comprises a semi-compliant balloon. In such examples, expandable member 20 incorporates both compliance and non-compliance in one or more portions (e.g., layers, sections, or sections) of the material. In addition, the base layer(s) of the bladder may be characterized by a first compliance, while the cover layer(s) of the bladder may have a second, different compliance. While described in connection with compliant and non-compliant examples, any material or configuration that allows expandable member 20 to expand in a predictable manner within a patient, including combinations of the properties of the material or configuration in compliance and non-compliance, is within the scope of the present disclosure. An example of a balloon that provides low straightening forces is disclosed in U.S. patent publication No. 2014/0276406 entitled "Conformable balloon devices and methods," and may also be adapted for use as expandable member 20 according to various embodiments.

The working length (W) of expandable member 20 may be from about 10mm to about 400mm, from about 10mm to about 250mm, or from about 10mm to 150 mm. Similarly, expandable member 20 can have a nominal diameter of from about 1mm to about 100mm, from about 1mm to about 60mm, or from about 2mm to 30 mm. For example, expandable member 20 can have a nominal diameter of about 2mm to about 10mm and a working length (W) of about 10mm to about 200mm, or a nominal diameter of about 6mm to about 25mm and a working length (W) of about 15mm to about 150 mm. It should be understood that expandable member 20 can have any suitable size and dimensions as desired for any suitable clinical application.

In various embodiments, expandable member 20 is attached or mounted to catheter 15 at leg 22 such that catheter 15 is in fluid communication with expandable member 20. For example, the catheter 15 may include one or more lumens, one of which may be in fluid communication with a lumen of the expandable member 20, optionally through an aperture in the catheter, for supplying inflation fluid to inflate the expandable member 20 in a tubular structure, such as the vasculature of a patient.

In some examples, the expansion element 10 further comprises a covering 27, such as the covering 27 described in application sequence No. 15/711,189 filed by the applicant on 21.9.2017 or 14/132,767 filed by the applicant on 18.12.2013 and published as US 2014/0172066.

For example, in some embodiments, the cover 27 includes a porous layer, such as, but not limited to, a porous fluoropolymer layer. According to certain embodiments, the porous fluoropolymer layer may include, but is not limited to, perfluoroelastomers and the like, Polytetrafluoroethylene (PTFE) and the like, and expanded fluoropolymers and the like. Non-limiting examples of expanded fluoropolymers include ePTFE, expanded modified polytetrafluoroethylene, and copolymers of expanded polytetrafluoroethylene. For example, an extruded ePTFE tube, a spirally wound ePTFE tube, or a cigarette-shaped wound ePTFE tube.

Various expanded PTFE mixtures, expanded modified PTFE, and expanded PTFE copolymers have been disclosed in the art, such as U.S. patent No. 5,708,044 to Branca; U.S. patent No. 6,541,589 to Baillie; U.S. patent No. 7,531,611 to Sabol et al; U.S. patent No. 8,637,144 to Ford; and U.S. patent No. 8,937,105 to Xu et al. U.S. publication No. US20160143579 discloses additional embodiments and methods of making embodiments suitable for use herein.

According to various embodiments, the multiple regions of the covering 27 (e.g., the first, second, and third regions) distributed along the first and second sections S1, S2 of the medical device 1100 are configured to move longitudinally in the distal direction over the expandable member 20 during the entire deployment of the expansion element 10 within the tubular structure of the patient, such that repeated inflation of the expandable member 20 may cause different regions of the covering 27 to apply multiple treatments or multiple functional surfaces to the tubular structure without removing the expansion element 10 from the body lumen in which it is positioned.

In some embodiments, cover 27 comprises a porous layer to which one or more coatings may be applied. One or more coatings can include therapeutic agents that can be applied to an area of covering 27 such that the therapeutic agent coating substantially covers the working length (W) of expandable member 20. Alternatively, one or more therapeutic agent coatings may be applied to a portion of covering 27 such that the therapeutic agent coating substantially covers the working length (W) of expandable member 20 and is disposed on at least one of opposing leg regions 22 and/or shoulder/tapered regions 23. The same therapeutic agent coating may be disposed on one or more areas of covering 27, one or more different therapeutic agent coatings may be disposed on one or more areas of covering 27, no coating may be disposed on one or more areas of covering 27, and/or the therapeutic agent coating may include one or more radiopaque elements, as described in further detail herein.

In some embodiments, the outer surface of the cover 27 and/or expandable member 20 may have a surface texture and/or surface features (see, e.g., fig. 3 and 4). The surface texture and/or surface features may be part of the covering 27 and/or the area of the expandable member 20 such that the surface texture and/or surface features extend along the working length (W) of the expandable member 20. Alternatively, the surface texture and/or surface features may be part of the covering 27 and/or the area of the expandable member 20 such that the surface texture and/or surface features extend along the working length (W) of the expandable member 20 and are disposed on at least a portion of the opposing legs 22 and/or shoulders/tapered portions 23. The same surface texture and/or surface features may be provided on one or more areas of covering 27, one or more surface textures and/or surface features may be provided on one or more areas of covering 27, no surface texture and/or surface features may be provided on one or more areas of covering 27, and/or the surface texture and/or surface features may include one or more radiopaque elements, as described in further detail herein.

The expansion member 10 may further include a cylindrical sheath 37 disposed around a portion of the cover 27 along at least a portion of the second section S2 of the medical device 1100. In some embodiments, the sheath 37 wraps around the entire circumference of the cover 27 and covers the entire length of the cover 27 disposed along the second section S2 of the medical device 1100. In other embodiments, the sheath 37 wraps around a portion of the circumference of the cover 27 and/or covers a portion of the length of the cover 27 disposed along the second section S2 of the medical device 1100. The sheath 37 can protect a therapeutic agent coating (e.g., a drug coating or a densified coating) on the outer surface of the covering 27 positioned beneath the sheath 37 during placement of the expansion member 10 in the tubular structure of the patient. The sheath 37 can also maintain a portion of the covering 27 positioned beneath the sheath 37 at the delivery diameter during use of the expansion element 10. In some embodiments, sheath 37 is bonded to a region of catheter 15 by an adhesive. For example, the sheath 37 may be coupled to a handle or hub at the proximal end 18 of the catheter 15. In other embodiments, sheath 37 is not bonded to catheter 15.

In various embodiments, the sheath 37 may comprise a polymer tube or a tube comprising other suitable materials including, but not limited to: thermoplastics such as, but not limited to, polymethylmethacrylate (PMMA or acrylic), Polystyrene (PS), Acrylonitrile Butadiene Styrene (ABS), polyvinyl chloride (PVC), modified polyethylene terephthalate (PETG), Cellulose Acetate Butyrate (CAB); semi-crystalline commercial plastics including Polyethylene (PE), High Density Polyethylene (HDPE), low density polyethylene (LDPE or LLDPE), polypropylene (PP), polymethylpentene (PMP); polycarbonate (PC), polyphenylene oxide (PPO), Modified polyphenylene oxide (Modified PPO), polyphenylene oxide (PPE), Modified polyphenylene oxide (Modified PPE), Thermoplastic Polyurethane (TPU); polyamides, such as nylon 11 and nylon 12, polyoxymethylene (POM or acetal), polyethylene terephthalate (PET, thermoplastic polyester), polybutylene terephthalate (PBT, thermoplastic polyester), polyimide (PI, Imidized plastic), polyamide-imide (PAI, Imidized plastic), polybenzimidazole (PBI, heat Imidized plastic); polysulfones (PSU), Polyetherimides (PEI), Polyethersulfones (PES), Polyarylsulfones (PAS); polyphenylene Sulfide (PPS), Polyetheretherketone (PEEK); a fluoropolymer comprising Fluorinated Ethylene Propylene (FEP), Ethylene Chlorotrifluoroethylene (ECTFE), ethylene-tetrafluoroethylene copolymer (ETFE), Polychlorotrifluoroethylene (PCTFE), polyvinylidene fluoride (PVDF), Perfluoroalkoxy (PFA), or combinations, copolymers or derivatives thereof. Other commonly known medical grade materials include elastomeric silicone polymers, polyether block amides (e.g., polyether block amides)). Specifically, the polyamide may include nylon 12, nylon 11, nylon 9, nylon 6/9, and nylon 6/6. In certain embodiments, PET, nylon, and PE may be selected for medical balloons used in coronary angioplasty or other high pressure applications. The specific choice of material depends on the desired characteristics/intended application of the capsule.

Fig. 3 and 4 illustrate additional or alternative features of the expansion member 10 for use with a medical device 1100. Fig. 3 illustrates another expansion member 101 of a medical device 1100 positioned on a catheter 106 according to some embodiments. The expansion member 101 optionally includes features similar to those described in connection with the expansion member 10, as additional or alternative features to the expansion member 101, and vice versa.

As shown, the expansion element 101 includes an expandable member or an expandable member 102. As shown in fig. 3, the first region 114 of the cover 104 may include at least one aperture 120. The first region 114 of the cover 104 can constrain a region of the expandable member 102 during inflation. The constraining action of the first region 114 of the cover 104 causes the expandable member 102 to inflate at the aperture 120 in the first region 114 of the cover 104. As shown in fig. 3, the portion of expandable member 102 that is inflated through aperture 120 of first region 114 of cover 104 has a diameter shown as "D1". As shown in fig. 3, a first region 114 of cover 104 positioned over expandable member 102 has a diameter "D2". The aperture 120 may include an opening or weakened location in the first region 114 of the cover 104. In this regard, the opening may be a hole, a cut, or any other discontinuous section of material of the first region 114 of the cover 104. For example, the hole may be formed by piercing the first region 114 of the cover 104. Alternatively, the aperture 120 may comprise an area of the first region 114 in which a region of material has been removed or otherwise weakened such that the weakened region at least partially deforms or detaches in response to inflation of the expandable member 102 and allows inflation beyond the first inflation state. The apertures 120 may be formed by any suitable means, including cutting, stamping, laser cutting, perforating and/or perforating/piercing and/or the like. In various embodiments, the first region 114 of the cover 104 may comprise a mesh structure.

In some embodiments, the therapeutic agent can be disposed on an inner or outer surface of expandable member 102 or a portion of covering 104, or disposed inside expandable member 102. For example, a coating including a therapeutic agent can be coated on the outer surface 108 of expandable member 102. When expandable member 102 protrudes through aperture 120, the therapeutic agent may be released at a localized portion of the body lumen. The therapeutic agent may include liquid or solid forms. The liquid form may have a desired viscosity suitable for the desired treatment. In some embodiments, the expansion member 101 can also have a coating comprising a therapeutic agent disposed on, within, configured to temporarily fill, or otherwise be integral with one or more of the first region 114, the second region 116, and the third region 118 of the covering 104.

The expandable member 102 may comprise any suitable compliant expandable member. As described above, the compliant expandable member may include a polymeric material. Example materials for the compliant expandable member include elastomers, such as polyurethane and silicone, natural rubber or latex products, synthetic rubber, such as nitrile butadiene, or other synthetic or naturally occurring polymeric materials. In various embodiments, the expandable member 102 may not be fully compliant, but more compliant than the first region 114 of the covering 104, and flexible enough to expand to a diameter larger than the diameter of the constrained first region 114 and thereby create the protrusions 122 of the expandable member 102 at a given pressure. Thus, a semi-compliant or non-compliant expandable member may be used. Optionally, the first region 114 of the cover 104 may include apertures that vary in size. Increasing the size of the aperture may allow for a wider (or "bolder") protrusion. By combining varying hole sizes with tapered cover profiles, the "scraping" effect of the assembly may be enhanced from proximal to distal, and vice versa, due to the different projection heights of expandable member 102.

In some embodiments of the present disclosure, the first region 114 of the covering 104 may include a wall having an area that is of reduced or less compliance as compared to other, more inflatable areas of the wall. Other areas are essentially "holes" that allow the underlying expandable member 102 to expand outward relative to the areas of reduced or less compliance of the first region 114 of the covering 104. The more inflatable region may include an upper inflation limit. The reduced compliance region may be formed by laser densification or by absorption with a polymer that reduces compliance in the absorption region. In an embodiment, the reduced compliance region has substantially the same thickness as the more inflatable region. Similarly, with other embodiments described herein, the first region 114 of the covering 104 may be formed via tape wrapping or extrusion, and may comprise ePTFE or any other material whose compliance may vary at discrete locations.

In various embodiments of the present disclosure, first region 114 of covering 104 may include any dimensionally-constrained form that acts to constrain expandable member 102 along various contact points. Alternatively, the first region 114 of the covering 104 may comprise a more non-compliant form than the expandable member 102, such that the expandable member 102 is constrained along the various contact points. Thus, the first region 114 of the covering 104 can be constructed of any material that does not significantly deform beyond the first expanded state during expansion of the expandable member 102.

With the described components, the compliance of at least a portion of the covering can be accommodated and/or the pattern of holes can be accommodated along at least a portion of the covering to control the topography of the expandable member assembly. For example, the pattern of apertures may include many small apertures to obtain a "fine-textured" pattern, or may include fewer larger openings to obtain a more "coarse-textured" pattern. As can be appreciated, any possible pattern of apertures or combination of patterns of apertures is contemplated herein. For example, a first region of the cover may include a pattern of grid-like holes and a second region of the cover may include a diamond pattern.

In other embodiments of the present disclosure, the expandable member extending through the covering may define ridges and grooves that run, for example, parallel to the longitudinal axis of the expandable member. In one embodiment, these provide blood perfusion between the expandable member and the vessel wall when the expandable member is expanded during treatment. In some embodiments, the first region 114 of the cover 104 may not have the aperture 120. In some embodiments, the first region 114 of the covering 104 may include only a therapeutic agent coating, such as, but not limited to, a drug coating.

Fig. 3 depicts a first region 114 of the covering 104 surrounding the expandable member 102 in an expanded profile. As shown in fig. 4, expandable member 102 can be deflated and first region 114 of cover 104 can be everted into the cover lumen of catheter 106 and can be pulled by an actuator (not shown) toward proximal end 112 of catheter 106. When the first region 114 of the cover 104 is pulled through the cover lumen of the catheter 106, the second region 116 of the cover 104 moves from its position around the catheter 106 and becomes positioned around the expandable member 102. The second region 116 of the cover 104 can have a different surface topography than the first region 114 of the cover 104.

In some embodiments, as shown in fig. 4, the second region 116 of the cover 104 can include a plurality of scored portions 124. Upon expansion, as shown in fig. 4, the scored portion 124 will partially separate from the surface 126 of the cover 104 and will form an outwardly extending protrusion. The ruptured portion of the cover 104 resulting from the rupture of the score 124 forms holes 128 in which the expandable member 102 may be at least partially exposed. In various embodiments, one or more of the scores 124 may be formed as through cuts in the material of the second region 116 of the cover that will not have to be broken in order to achieve the desired effect.

Scoring and subsequent rupturing of the score may enable the sharp object to be inserted into the body in a substantially unsharpened state, and then provide for deployment (deployment) of the sharp object at a particular time. In addition, scoring and subsequent rupturing may aid in the delivery of the therapeutic agent. For example, a therapeutic agent can be disposed between expandable member 102 and second region 116 of covering 104. The covering 104 can seal the therapeutic agent over the expandable member 102 such that when placed into the body, the therapeutic agent is substantially retained in the space between the expandable member 102 and the covering 104. When the scored portion 124 of the cover 104 is ruptured, the therapeutic agent may be released into a localized portion of the body. In some embodiments, the second region 116 of the covering may remove plaque and/or other deposits from the lumen wall. In some embodiments, a therapeutic coating can be applied to the lumen wall through the first region 114 without removing the medical device 1100 from the lumen prior to removing plaque and/or other deposits from the wall with the scored portion 124 of the second region 116 of the cover 104.

Any of a variety of additional or alternative expansion member features are contemplated, such as, for example, primarily scoring and cutting features, etc., drug coatings, controlled topography features, and/or off-axis expansion features. Further, the expansion element may take any of a variety of forms, including a cage, mesh, stent, oscillating member, and the like.

Examples of expansion elements using varying diameters

To obtain an increasing expansion diameter, in some examples, multiple expansion elements (e.g., balloons) with different nominal sizes (e.g., diameters) are employed as part of a treatment procedure. In particular, a set of expanding elements of increasing nominal diameter may be used one after the other in order to vary the maximum diameter expansion to which the tissue is exposed. In some examples, the medical device 1100 may include a plurality of balloon catheters that may be coupled to the pressure modulator 1104, each balloon catheter including a balloon of varying diameter. In further examples, a single catheter includes multiple dilation elements having different nominal values.

Examples of Using an Adjustable diameter expansion element

To obtain increasing expansion dimensions (e.g., diameters), some examples include the use of expansion elements that incorporate multiple nominal dimensions or stop points that exhibit or otherwise achieve at different expansion forces (e.g., pressures). It will be appreciated that this practice may be used in conjunction with or as an alternative to a plurality of expansion elements (as described above) having different nominal dimensions.

Various diameter expansion features (nominal size limits and characteristics) may be implemented to achieve varying (e.g., increasing) nominal sizes. The base layer or layers forming the capsule or the cover of the capsule may be designed with one or more stopping points in the radial and/or axial direction. For example, U.S. patent application publication No. 2014/0172066, filed on 12/18/2013, describes a capsule device that utilizes an expanded polymer, such as a fluoropolymer material that optionally absorbs an elastomer.

Upon inflation, the balloon may be inflated circumferentially up to a stop point beyond which the force required for inflation is significantly increased. The stop point may be due to a material that incorporates the stored length feature. This "stored length" feature may be incorporated into the base material of the bladder or the cover of the bladder. In some examples, the serpentine shaped fibril microstructure of the fluoropolymer material occupies at least a portion of the stored length characteristics and radial expansion capability. In addition, such balloon devices may also be suitably longitudinally inflated (or longitudinally weakened) to impart or increase longitudinal length under longitudinal stress that may otherwise occur during radial expansion.

In some methods of manufacturing such balloons, construction is by circumferentially wrapping (forming the base or cover layer of the balloon) an elastomeric absorbent expanded polymeric material having a stored length at the delivery diameter. Regardless, in various examples, such a bladder may expand to a first limit or stop point at a first pressure and then expand beyond the first limit to a second limit or stop point at a second, higher pressure. In this way, the nominal size (e.g., diameter and/or length) of the balloon can be adjusted in a stepwise manner. By incorporating additional storage length layer(s) at different diameter(s), multiple stop points can be achieved for any of the expansion elements described herein, as desired.

Various other and/or alternative expansion element configurations and expansion features. For example, any other balloon design such as disclosed in U.S. patent No. 5,752,934 filed on 9/18/1995 and provisional patent application No. u.s.62/661,942 filed on 24/4/2018 by the applicant may be implemented as desired.

Pressurized source examples

The pressurized source 1104 may be coupled to the conduit 15 via the port 26 of the conduit 15. The pressurized source 1104 may be any suitable inflation-deflation device, such as a syringe, an internal insufflator/expander, a pump, or any other means for directing inflation fluid through the catheter 15 and into the expandable member 20. Additional examples may include, for example, one or more of a piston drive, a screw drive, an air compressor, an air reservoir, a servo motor, a piezoelectric motor, and/or a pressurized fluid reservoir. The pressurized source 1104 may include a manual component (e.g., a syringe stopper) coupled to an automated component (e.g., a cylinder, an air compressor, or other suitable component).

Pressurization 1104 may, according to some embodiments, push fluid into a chamber of an expandable member (e.g., expandable member 20) via catheter 15 and withdraw fluid from the chamber to inflate and deflate the expandable member. The pressurized source 1104 may include a fluid reservoir (not shown) or be connected to a separate fluid reservoir (also not shown). To assist in controlling the diameter of the expandable member(s), the catheter 15 and expandable member 20 can be aspirated (removing air and replacing it with fluid) prior to inflating expandable member 1100 with inflation fluid. The inflation fluid used to aspirate the catheter and the expandable member and/or to inflate expandable member 20 may include a contrast agent (e.g., an imaging agent that allows imaging of the expandable member by an imaging modality), or a mixture of a contrast agent and saline.

Controller examples

The controller 1106 optionally includes one or more mechanical timing mechanisms, such as gears, linkages, or other mechanisms, for causing the medical device to cycle in size according to a predetermined treatment procedure. In some examples, the therapy program 1110 and its various features and components can be implemented in one or more computing devices (e.g., personal computers, laptops, servers, controllers) containing one or more processors and memory. For example, the therapy program 1110 may be implemented using firmware, integrated circuits, and/or software modules within one or more computing devices that interact or are combined with each other. In certain embodiments, the methods disclosed herein for the therapy program 1110 and the methods outlined in the figures may be implemented using computer readable instructions/code stored in memory (or other form of storage) for execution by one or more processors.

In some embodiments, the memory includes computer-readable media in the form of volatile and/or nonvolatile memory and may be removable, non-removable, or a combination thereof. Examples of the medium include a Random Access Memory (RAM); read Only Memory (ROM); an Electronically Erasable Programmable Read Only Memory (EEPROM); flashing; an optical or holographic medium; magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices; data transmission; and/or any other medium that can be used to store information and that can be accessed by a computing device, such as, for example, quantum state memory and/or the like. In some embodiments, the memory stores computer-executable instructions for causing the processor of the controller 1106 to implement aspects of embodiments of the system components discussed herein and/or to perform aspects of embodiments of the methods and programs discussed herein.

Computer-executable instructions may include, for example, computer code, machine-useable instructions, and the like, such as program components that are executable by one or more processors associated with the controller 1106, for example. Many different programming environments may be used to program components, including various languages, development kits, frameworks, and/or the like. Some or all of the functionality contemplated herein may also or alternatively be implemented in hardware and/or firmware.

The controller 1106 may be configured to operate the medical device 1100 in accordance with a treatment procedure 1110, or portions thereof, and may be a separate component or included in any other system component, such as the pressurization source 1104, the power source 1108, or the medical device 1100, as desired. The controller 1106 may include or be connected to a separate user interface (not shown). The controller 1106 may include at least one processor (e.g., a microprocessor) that executes software and/or firmware stored in a memory of the controller 1106. The software/firmware code contains instructions that, when executed by the processor, cause the controller 1106 to operate the medical device 1100 in accordance with the therapy program 1110. Controller 1106 may alternatively comprise one or more Application Specific Integrated Circuits (ASICs), Field Programmable Gate Arrays (FPGAs), Digital Signal Processors (DSPs), hardwired logic, or a combination thereof.

In some examples, the controller 1106 receives information from a plurality of system components (e.g., pressure sensors, current sensors, feedback loops, or any other source of information for components) and feeds the information (e.g., pressure data, drug delivery data, user data) into a control algorithm that determines at least one therapy program parameter that may, in part, control the operation of the medical device 1100. In some particular embodiments, the controller 1106 can receive expansion element data (e.g., balloon pressure, whether measured directly or indirectly by a proxy such as a current change in a motor) from the medical device 1100 and/or the pressurized source 1102 and user data from a user interface (not shown). In certain embodiments, controller 1106 receives user data from a remotely located device (e.g., a server, a doctor's computing/communication device, etc.).

Examples of Power sources

In both the automatic and non-automatic examples, the power source 1108 may include a physical user input, such as a rotating handle (e.g., where a mechanical timing mechanism is used to implement the treatment program). The power source may also be electrical, chemical or electrochemical in nature. In some examples, power source 1108 is a battery housed with the other components of system 1102.

Test system

Fig. 5A and 5B illustrate a test device for evaluating efficacy of a treatment procedure according to various examples. As shown in fig. 5A, in the testing apparatus, the pressurization source 1104 (fig. 1) comprises a microfluidic flow control system including one or more pressure and/or vacuum pumps, such as those sold under the trade name "Elveflow", flow regulators, air filters and air compressors, and syringes for pressurizing the conduits used as the medical device 1100 (fig. 1). Controller 1106 (fig. 1) comprises a laptop PC and power source 1108 comprises an electrical outlet. Fig. 5B is a schematic diagram of various system components for further understanding. Fig. 5C is a block diagram of one design of a controller for controlling a pressurization source, according to some examples. In some embodiments, the pressure sensor is a 4-20mA transmitter that pulls 4mA at 0% and 20mA at 100%. A 499 ohm resistor can be used to convert current to voltage and an RC filter can be used to suppress switching noise from the 24V power supply. Data from the system may be recorded to verify the efficacy of the treatment program and/or to provide a closed feedback loop to the system as desired.

Parameters of a treatment program

As previously mentioned, the treatment procedure, or portions thereof, may be performed manually, or may be automated through the use of mechanical or electronic methods.

In some examples, the treatment procedure includes cycling the expansion element between the expanded state and the contracted state or configuration at a desired frequency (including any range of frequencies). In some examples, the treatment procedure includes cycling the expansion element at a first frequency (e.g., from 0.1 to 10Hz), at a second frequency different from the first frequency (e.g., from 0.1 to 10Hz), at a third frequency different from the first frequency and/or the second frequency, and so on. In addition to varying the frequency, the treatment program may vary primarily in terms of, for example, minimum dilation size/pressure per cycle, maximum dilation size/pressure per cycle, cycle amplitude, cycle frequency, dwell time, and overall program length. Further, for example, the treatment procedure may be configured to treat a particular tissue site and/or type of medication.

The following table lists non-limiting examples of expected pressure ranges, balloon types for the medical device 1100, pressure increments, cycling frequencies, calcium fractions of specific tissue sites for which treatment procedures are to be applied, nominal balloon diameters available for the medical device 1100, and the types of diseases for which treatment procedures are to be constructed/applied. These various parameters can be combined in any desired combination, and each range includes not only the specific ranges listed in the following table, but also any value or range between the values listed in table 1. In other words, table 1 should not be construed as limiting in nature, but rather as an inventive concept within the scope of the present disclosure.

Table 1.

Cyclic expansion/treatment profile for treatment procedure

Each of the following examples relates to a treatment profile for a treatment procedure (or a portion thereof), wherein one or more expansion elements expand and contract at a treatment frequency having a value of 0.1Hz to 10Hz, the one or more expansion elements expanding and contracting between a first dimension D1n at a corresponding first force F1n and a second dimension D2n at a counter stress F2n, the second dimension D2n and the counter stress F2n being greater than the first dimension D1n and the first force F1n, respectively. The first and/or second dimensions and forces may be increased, held constant, or decreased as desired throughout the treatment procedure 1110.

Fig. 6 is an example of a treatment procedure (or a portion thereof) in which one or more dilation elements that dilate and contract between a first dimension D1n and a second dimension D2n that is larger than the first dimension D1n are dilated and contracted at a treatment frequency having a value of 0.1Hz to 10 Hz. In the example shown in fig. 6, a single cycle (n ═ 1) is shown, and the treatment curve includes a second size of hold times or dwell times dwell (n) for three minutes (min), but there are various dwell times ranging from 1 second(s) to 60 minutes (min), including any value at 1 second(s) intervals or any range of values in between. In example 1 shown in fig. 6, the maximum force applied by the associated expansion element ranges from 0 newtons (N) to over 30 newtons (N), although any of a variety of forces may be considered, including any value in the 0.5 newtons (N) interval of the total force N or any range of values therebetween. After the dwell time dwells (n), the expansion element is allowed to contract and return to an extension of, for example, about 0 millimeters (mm).

Fig. 7 is an example of a treatment procedure (or a portion thereof) in which one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expanding and contracting between a first dimension D1n and a second dimension D2n greater than the first dimension D1n via a progressively cycling expansion curve that includes a second dimension D2n that increases in value from an initial value D2n greater than a nominal dimension of the treatment site and a subsequent value D2n +1 greater than the initial value D2n, the expansion elements expanding to the subsequent value D2n +1, where n ranges from 0 to a total number of cycles (3 cycles in example 2 of fig. 7, although any number is contemplated). As shown, the second value increases in extension in increments of about 2mm, accompanied by increasing force values, although any of a variety of incremental increments are contemplated.

For each cycle in example 2 of fig. 7, the treatment profile includes a retention time or dwell time dwell (n) of the second size for 60 seconds(s), although there are various dwell times ranging from 1 second(s) to 60 minutes (min), including any value at 1 second(s) intervals or any range of values in between. For example, after the dwell time dwell (n) of each cycle, the expansion element is allowed to contract and return to an extension of about 0, although in other examples, another cycle begins before the extension returns toward zero (e.g., approaches or moves in that direction).

Fig. 8 is another example of a treatment procedure (or a portion thereof) in which one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expand and contract between a first dimension D1n and a second dimension D2n that is greater than the first dimension D1n via an increasing cyclic expansion curve that includes a second dimension D2n that increases in value from an initial value D2n that is greater than a nominal dimension of the treatment site and a subsequent value D2n +1 that is greater than the initial value D2n, the expansion elements expanding to the subsequent value D2n +1, where n ranges from 0 to total cycles.

As shown in fig. 8, the second value increases in extension/dimension in increments of about 0.25mm with increasing force values, although any of a variety of incremental increases are contemplated.

For each cycle in example 3 of fig. 8, the treatment profile includes a retention time or dwell time dwell (n) of the second dimension for 60 seconds(s), exhibiting an increased amount of force relaxation during dwell time dwell (n) for each cycle. For example, any of a variety of residence times from 0 seconds(s) to 1 second(s) to 60 minutes (minutes) are contemplated, including any value at 1 second(s) intervals or any range of values therebetween. For example, after the dwell time dwell (n) of each cycle, the expansion element is allowed to contract and return to an extension of about 0, although in other examples, another cycle begins before the extension returns toward zero (e.g., approaches or moves in that direction).

Fig. 9 is yet another example of a treatment procedure (or a portion thereof) in which one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expand and contract between a first dimension D1n and a second dimension D2n that is greater than the first dimension D1n via an increasing cyclic expansion curve that includes a second dimension D2n that increases in value from an initial value D2n that is greater than a nominal dimension of the treatment site and a subsequent value D2n +1 that is greater than the initial value D2n, the expansion elements expand to the subsequent value D2n +1, where n ranges from 0 to total cycles.

As shown in fig. 9, the second value increases in extension/dimension in increments of about 0.2mm with increasing force values, although any of a variety of incremental increases are contemplated.

For each cycle in example 4 of fig. 9, the treatment curve does not include a hold time or a dwell time dwell (n) of zero at the second dimension D2n of each cycle. For example, after each cycle, the expansion element is allowed to contract and return to an extension of about 0 immediately or nearly immediately, although in other examples another cycle begins before the extension returns toward zero (e.g., moves near or in that direction).

Fig. 10 is yet another example of a treatment procedure (or a portion thereof) in which one or more dilation elements that dilate and contract between a first dimension D1n and a second dimension D2n that is larger than the first dimension D1n are dilated and contracted at a treatment frequency having a value of 0.1Hz to 10 Hz. A single cycle is shown, although multiple cycles may be employed.

As shown in fig. 10, the second force F2n is maintained relatively constant (e.g., by measuring the inflation pressure on the expansion member using a closed feedback loop) for a desired period of time (e.g., 130 seconds(s), although any force maintenance period is contemplated). During the constant force period F2n (constant), the extension or size is increased by a desired amount (e.g., 0.7 millimeters (mm), although any value is contemplated).

Fig. 11 shows another example of the treatment procedure (or a portion thereof) of example 6, wherein the one or more expansion elements expand and contract at a treatment frequency having a value from 0.1Hz to 10Hz, the one or more expansion elements expand and contract between a first dimension D1n and a second dimension D2n that is greater than the first dimension D1n via an increasing cyclic expansion curve that includes a second dimension D2n that increases in value from an initial value D2n that is greater than a nominal dimension of the treatment site and a subsequent value D2n +1 that is greater than the initial value D2n, the expansion elements expand to the subsequent value D2n +1, where n ranges from 0 to a total number of cycles. In addition, the value of the first dimension D1n is also increasing from an initial value D1n and a subsequent value D1n +1 that is greater than the initial value D1n, where n ranges from 0 to the total number of cycles.

As shown in fig. 1, the second value D2n increases in extension/size in increments of about 0.3mm with increasing force values (increasing cycle to cycle), although any of a variety of incremental increments are contemplated. Similarly, the first value D1n is incrementally increased in extension/dimension with incremental force values (increasing cyclically to cyclically), although any of a variety of incremental increments are contemplated.

For each cycle in example 6 of fig. 11, the treatment profile includes a dwell time dwell (n) for each cycle, exhibiting increased force relaxation during the dwell time dwell (n) for each cycle. For example, after each cycle, the expansion element is allowed to contract and return to an extension of about 0 immediately or nearly immediately, although in other examples another cycle begins before the extension returns toward zero (e.g., moves near or in that direction).

Any of the foregoing treatment profile characteristics may be combined, modified or enhanced with the characteristics of other treatment profiles.

In any example, the second dimension D2n may be constant for each cycle, may be increasing for each cycle, or may be increasing and/or decreasing for alternating cycles. The second dimension D2n can be increasing at a constant rate or a varying rate. The second dimension D2n may be incremented by 10% to 500% as a percentage of the previous second dimension value D2n, including any value within this range or within any range within the range in 0% increments.

In any example, the first dimension D1n may be constant for each cycle, may be increasing for each cycle, or may be increasing and/or decreasing for alternating cycles. The first dimension D1n can be increased at a constant rate or a varying rate. The first dimension D1n may be incremented by 0% to 500% as a percentage of the previous first dimension value D1n, including any value within this range or within any range within the range in 1% increments.

In any example, the dwell time dwell (n) may be constant for each cycle, may be increasing for each cycle, or may be increasing and/or decreasing for alternate cycles. The residence time of the circulation dwell (n) can be varied at a constant rate or at a varying rate. The residence time dwell (n) may vary from 0% to 500% as a percentage of the previous residence time dwell (n), including any value within this range or within any range within the range in 1% increments.

Similarly, in any example, the treatment program may exhibit a relatively constant amount of force relaxation during each dwell time dwell (n), an increasing amount of force relaxation during a subsequent dwell time dwell (n), or a variable amount of force relaxation relative to a previous dwell time dwell (n) according to a particular cycle of the treatment program.

The amplitude change per cycle or the difference between D1n and D2n may be constant for each cycle, may be increasing for each cycle, or may be increasing and/or decreasing for alternating cycles. The amplitude can be varied at a constant rate or a varying rate. The amplitude of each cycle may vary by 0% to 500% as a percentage of the amplitude of the previous cycle, including any value within this range or within any range within the range in 1% increments.

Further, the treatment procedure may be expressed in terms of force (e.g., stress or pressure) rather than size. In any example, the second force F2n may be constant for each cycle, increasing for each cycle, or increasing and/or decreasing for alternating cycles. The second force F2n can be ramped up at a constant rate or a varying rate. The second force F2n may be incremented by 10% to 500% as a percentage of the previous second force value F2n, including any value within this range or within any range within the range in 0% increments.

In any example, the first force F1n may be constant for each cycle, may be increasing for each cycle, or may be increasing and/or decreasing for alternating cycles. The first force F1n can be increasing at a constant rate or a varying rate. The first force F1n may be incrementally increased by 0% to 500% as a percentage of the previous first force value F1n, including any value within this range or within any range within the range in increments of 1%.

In any example, the treatment procedure can include providing a cycle in which the first dimension D1n and the second dimension D2n represent the first diameter and the final diameter. The final diameter is the maximum diameter and represents the final diameter desired in the treatment protocol for that cycle. However, the treatment procedure may include any number of intermediate diameters Dintn greater than D1n and less than D2 n. The treatment regimen may include starting from the first dimension D1n and expanding to a second or final diameter D2, preferably cycling between the first diameter D1n and the intermediate diameter Dintn, up to a second or final diameter D2n, wherein cycling between the first diameter D1n and the intermediate diameter Dintn includes gradually increasing the intermediate diameter Dintn until the second diameter D2n is reached. Particular examples may include cycling from a first diameter D1n to a first intermediate diameter Dint1, back to the first diameter D1n, up to a second larger intermediate diameter Dint2, back to the first diameter D1n, and up to a third larger intermediate diameter Dint3, until the cycle reaches a target, second or final diameter D2 n.

In other embodiments, cycling may include cycling from the first diameter D1n to a first intermediate diameter Dint1, back to the first diameter D1n, up to a second larger intermediate diameter Dint2, back to the first diameter D1n, up to a third larger intermediate diameter Dint3, and back to the second intermediate diameter Dint2 until the cycle reaches the target, second or final diameter D2 n. Within the scope of the present disclosure, combinations of various cycling schemes may include combinations of the cycles disclosed above, wherein after each pressure drop, the diameter may be incrementally increased to first diameter D1n or a previous intermediate diameter Dintn (either an immediately previous intermediate diameter Dintn or any intermediate diameter Dintn that precedes a current intermediate diameter Dintn).

Thus, in some configurations, the target site or vessel to be treated has a starting vessel diameter and a target final vessel diameter, wherein the starting vessel diameter is less than the target final vessel diameter. The second diameter D2n of the expansion member is configured to achieve the target final vessel diameter. In some embodiments, the expansion element includes a stop that limits expansion of the expansion element beyond a predetermined diameter corresponding to a diameter operable to achieve a target final vessel diameter. In some embodiments, the stop may be achieved by selecting a material for the expansion element that is radially compliant as compared to a fully radially compliant expansion element. As previously mentioned, this may also be achieved via the use of a cover.

It will also be appreciated from the foregoing that the number of cycles per treatment program may be selected as desired for the particular treatment to be administered. Any of a variety of other method features can be incorporated into a particular treatment procedure, including the user and/or the system rotating, sliding, or otherwise displacing the relative position of one or more expansion elements of the system.

The invention of the present application has been described above generally and with reference to specific embodiments. It will be apparent to those skilled in the art that various modifications and changes can be made to the embodiments without departing from the scope of the disclosure. Thus, it is intended that the embodiments cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.