Patent ID: 12214147

DETAILED DESCRIPTION

Angioplasty Catheter System

The various components and features of the angioplasty balloon catheter system of the present invention are next described with reference toFIGS.1through11.FIG.1illustrates a perspective view of an angioplasty balloon catheter in accordance with the present disclosure. InFIG.1, the balloon catheter10includes, from left to right, a catheter tip12, an inflatable member or balloon13, an elongated tubular member or catheter shaft15, a kink protection sleeve16, and a manifold17, that in turn comprises an inflation port18and a guide wire port19. The elongated member15extends from the catheter tip12or distal end of the catheter to the guide wire port19or proximal end of the catheter. The elongated tubular member further15includes at least one lumen that is in fluid communication with the inflatable member13mounted adjacent to the distal end12of the catheter10. In the implementation shown inFIG.1the catheter shaft15includes two internal lumens: (1) a first lumen intended as an inflation lumen connected to the inflation port18; and (2) a second lumen intended as a guide-wire lumen connected to the guide-wire port19. The angioplasty catheter is shown in an over-the wire configuration, wherein a guidewire11extends from an opening at the distal end or tip12of the catheter through an opening at the guidewire port19at the proximal end.

OTW/RX Configuration

FIG.2illustrates a cross-lateral view of a dual-lumen configured inflatable member of an angioplasty balloon catheter of the present disclosure for use in over-the-wire (OTW) configuration. InFIG.2, the balloon catheter system10ofFIG.1is shown in an over-the-wire configuration20, wherein the catheter shaft15comprises a dual-lumen consisting of a guide wire lumen25and an inflation lumen26. The guide wire lumen25is disposed along the entire length of the catheter10, and extends from an opening at the catheter tip12or distal end through the balloon13to an opening at the guide wire port19at the proximal end of the catheter. This particular guide-wire lumen configuration enables over-the-wire (OTW) operation of the catheter, meaning that the angioplasty balloon catheter can be slideably mounted onto a guide-wire11and translated in either direction along an entire indwelling portion of the guide-wire lumen during insertion of a portion of the catheter shaft into a patient's blood vessel. The OTW configuration therefore may utilize up to the complete usable length of the catheter, which spans from the distal end of the kink-protection sleeve16to the distal end or catheter tip12of the catheter.

FIG.3illustrates a cross-lateral view of a dual-lumen configured inflatable member of an angioplasty balloon catheter of the present disclosure for use in rapid-exchange (RX) configuration. InFIG.3, the balloon catheter system10ofFIG.1is shown in a rapid-exchange configuration30, wherein the catheter shaft15comprises a single lumen29that distally extends into a dual-lumen portion consisting of a guide wire lumen25and an inflation lumen26. The guide wire lumen25extends from an opening at the catheter tip12or distal end to a guide wire port27located proximal to a most proximal lobe22of the balloon13, and therefore extends at least partially through the elongated member15. The guide wire port27may further include a ramp-like surface28to aid in guiding a guidewire11through the opening27. In comparison to the previously shown OTW configurations ofFIG.1andFIG.2, the RX configuration30ofFIG.3does not require that an additional guidewire port19is present at manifold17. Thereby, the guide-wire lumen configuration enables rapid-exchange (RX) operation of the catheter10, meaning that the balloon catheter can be slideably mounted onto a guide-wire11and translated in either direction such that the guidewire passes along a portion of the guide-wire lumen25during insertion of a portion of the shaft into a patient's blood vessel. The RX configuration30therefore may utilize a shorter usable length of the catheter, which spans from the distal end of the guide wire port27to the distal end or catheter tip12of the catheter. As a result, the RX configuration enables using guidewires of considerably smaller length in comparison to the OTW configuration. In RX operation, the guide-wire11is partially exposed alongside the catheter shaft, when located within an indwelling portion, whereas in OTW operation, the guide-wire11is fully shielded by the catheter shaft, when located within the indwelling portion.

Shown both inFIG.2andFIG.3, the inflation lumen26extends from the inflation port18adjacent to the proximal end of the catheter10to an opening24connected to an interior space or lumen23of a first lobe22of the balloon13. The interior lumen23of the first lobe22of the balloon13in turn is shown fluidly connected to one or more adjacent lobes via one or more waist portions21. Thereby, therapeutic and diagnostic liquids as well as gases, including contrast-agent and saline formulations, drug-formulations, air, and other such liquids and/or gases, may be transferred, under positive pressure inside the inflation lumen or at the inflation port, respectively, from the inflation port18through the inflation lumen26to one or more lobes22of the inflatable member13, resulting in an inflation of the catheter balloon. The various liquids and/or gases are transferred, under negative pressure inside the inflation lumen26or at the inflation port, respectively, from the inflated balloon13back through the inflation lumen and out through the inflation port18, deflating the catheter balloon. “Positive pressure” and “negative pressure” designate pressures which are larger than, or smaller than, respectively, the pressure around balloon13.

Inflatable Member Configuration

FIGS.4-10illustrate cross-sectional views of an inflatable member of the angioplasty balloon catheter in accordance with the present disclosure. InFIG.4, an inflatable member13is shown partially affixed to a catheter shaft15of the angioplasty balloon catheter10. The inflatable member13is formed from at least two lobes32,34, spaced apart by one or more waist portions44,45. The waist portion44has a lower base length33and an upper base length37, and two legs91,92. In turn, a (mantle) length39of the inflatable member13is provided through the sum of the individual lengths36, and38of the at least two lobes32,34, and the individual length37(L) of the one or more waist portions44,45, respectively. Further, the upper base of the waist portion44of the inflatable member13exhibits a first, radial distance or depth40relative to the lower base of the waist portion44, and the lower base of the inflatable member13exhibits a second, radial distance or depth41relative to a rotational axis (indicated as a dash-dotted line) of the inflatable member13. Consecutively, the sum of the first and second distances, or depths40,41of the waist portion44yield an outer radius42(R) of the inflatable member13. The one or more waist portions44of the at least two or more lobes32,34of the inflatable member13can exhibit one or more length37(L) that is adapted to a specific intended use or clinical indication, in particular including the controlled, and sequential cracking of a lesion, and/or the intramural delivery of drugs. In the case of drug delivery applications, the one or more length37(L) of the one or more waist portion44,45of the at least two or more lobes32,34of the inflatable member13can preferably be adapted to a length aspect of the lesion, and the length selected from at least a set of ranges that includes 0-240 mm, 5-10 mm, 10-30 mm, 30-60 mm, 60-90 mm, 90-120 mm, 120-150 mm, 150-180 mm, 180-210 mm, and 210-240 mm. In the case of controlled lesion cracking, the one or more length37(L) of the one or more waist portion44,45of the at least two or more lobes32,34of the inflatable member13can preferably be adapted to a diameter aspect of the lesion, and the length selected from at least a set of ranges that includes 0-20 mm, 1-2 mm, 2-4 mm, 4-6 mm, 6-8 mm, 8-10 mm, 10-12 mm, 12-14 mm, 14-16 mm, 16-18 mm, and 18-20 mm. Because the angioplasty catheter of the current disclosure is directed to the combined intended uses of drug delivery and controlled lesion cracking, a combination of both of the above sets of ranges can be desired, and thus, the one or more waist portions44of the at least two or more lobes32,34of the inflatable member13can exhibit one or more length37(L) selected from the above two sets of ranges that are each adapted to a length and diameter aspect of the lesion. Of the above two sets of length ranges, the smaller, diameter-aspected length range constitutes the preferred range. Therefore, as a specific feature of the inflatable member of the present disclosure, the waist portion44can preferably exhibit a length37(L) not greater than two times the radius42(R) of the inflatable member. The upper base length37of the waist portion44,45therefore can be designed to not dimensionally exceed an outer diameter43of the inflatable member in a pressurized state. Specific technical effects of the segmentation of the inflatable member into the at least two or more lobes via one or more waist portions will be further described in reference toFIGS.12-20.

In the above provided example, the distal and proximal end of the inflatable member13are each affixed to a portion of the catheter shaft15to form a fluid-tight space or interior lumen23between the inner surface of the inflatable member and the outer surface of the catheter shaft. In reference to the description ofFIGS.2-3, an inflation lumen26extends from the inflation port18adjacent to the proximal end of the catheter10to an opening24that is connected to the interior lumen23of the first, or most proximal of the at least two lobes32,34of the inflatable member13. Because in this implementation the waist portion44is not adhered to the catheter shaft15, as opposed to the waist portion45, the interior lumen23of the inflatable member13in turn fluidly connects to the one or more adjacent lobes32via the one or more waist portions44. In alternate implementations, one waist portion45, or more waist portions44,45can be provided not attached to the wall of the catheter shaft15to fluidly connect between the one or more lobes32,34. Therefore, the one or more waist portion44,45of the inflatable member13of the balloon catheter10is one or more of: attached, partially attached and not attached to the elongated member15.

For enabling angiographic visibility, radiopaque markers31,35are attached to the catheter shaft15at shaft locations that indicate a lobe position, and/or demarcate the proximal and distal ends or mantle surface of the inflatable member13. In reference toFIG.1, the inflatable member13of the present disclosure may include a plurality of lobes, for example the inflatable member or balloon may have 2 to 20, 2 to 15, 2 to 10, 3 to 8, 4 to 6 and 2 to 4 lobes. Further, the number of lobes can be selected from an odd or even number. The actual number of lobes can be governed, among others, from a set of balloon lengths and diameters suitable and effective for treating complex lesions.

Generally, in an unpressurized state, the at least two lobes32,34of the inflatable member13are provided each folded and pleated, such that subsequent pressurization of the inflatable member individually unfolds each of the two or more lobes. Preferably a number of pleats of the at least two lobes32,34of the folded and pleated inflatable member13in an unpressurized state is an uneven number equal or greater than three.

Further, a flap length of the at least two lobes32,34of the folded and pleated inflatable member13is preferably selected from at least a range of lengths from about a ratio between 0.25 to 0.75, and more preferably, from a ratio of 0.5 to 0.66 of the radius42of the inflatable member, wherein the maximum flap length of the inflatable member is determined by the first depth40of the waist portion44,45, thereby reducing a torsional load that is transferred between the inflatable member and an area to be treated (65,66). The second depth41relative to a rotational axis of the at least two lobes32,34of the folded and pleated inflatable member13is preferably selected from a remainder of the above ratio, that is preferably 0.25 (1-0.75) to 0.75 (1-0.25), and more preferably 0.34 (1-0.66) to 0.5 (1-0.5) of the radius42of the inflatable member. Further, the second depth41is preferably not exceeding a ratio greater than 0.5 relative to a nominal diameter43of the inflatable member in a pressurized state. In additional implementations, at least one of the number of pleats and one of the flap length of the at least two lobes32,34of the folded and pleated inflatable member13in an unpressurized state are varied.

Preferably, a length39of the inflatable member13is selected from at least a set of ranges that includes 0-240 mm, 5-10 mm, 10-30 mm, 30-60 mm, 60-90 mm, 90-120 mm, 120-150 mm, 150-180 mm, 180-210 mm, and 210-240 mm. In addition, a length36,38of the at least two lobes32,34of the inflatable member13is selected from at least a set of ranges that includes 0-240 mm, 1-5 mm, 5-10 mm, 10-30 mm, 30-60 mm, 60-90 mm, 90-120 mm, 120-150 mm, 150-180 mm, 180-210 mm, and 210-240 mm. Further, the length36,38of the at least two lobes32,34of the inflatable member13can include multiple, different lengths.

Preferably, a diameter43of the at least two lobes32,34of the inflatable member13is selected from at least a set of ranges that includes 0-20 mm, 1-2 mm, 2-4 mm, 4-6 mm, 6-8 mm, 8-10 mm, 10-12 mm, 12-14 mm, 14-16 mm, 16-18 mm, and 18-20 mm. In addition, a diameter43of the at least two lobes32,34of the inflatable member can include multiple, different diameters.

Based on the foregoing, at least one of the length and one of the diameter of the at least two lobes32,34can be varied.

Further, the inflatable member13of the balloon catheter10can comprise a distal predilatation portion and a proximal dilatation portion. In the above, the predilatation portion can consist of at least four lobes, each length36,38selected from a range of not greater than 1-10 mm, preferably 1-5 mm; and each diameter43in an unpressurized state selected from a range of not greater than 0.5-2 mm, preferably 1-2 mm; and the dilation portion can consist of at least four lobes, each length36,38selected from a range of greater than 1-10 mm, preferably 1-5 mm; and each diameter43in a pressurized state selected from a range of greater than 0.5-2 mm, preferably 1-2 mm.

In additional implementations, the lengths36,38and radii41,42, or diameters43of the at least two or more lobes, and the lengths37and depths40,41of the one or more waist portions can be selected from the same, similar or different, lengths, radii, or depths, and either lobes and/or waist portions can be spaced at equal, similar or different distances from one another, depending on their specific use.

In the provided examples ofFIGS.1-4, the dual lumens of the inflatable member13are arranged in a side by side (or parallel) configuration. In alternate implementations, more than two lumens can be present, and the lumens provided in parallel and/or co-axial arrangement, as well as combinations selected therefrom. Such examples will be shown inFIGS.5-7.

For further illustration,FIG.5shows an implementation of the inflatable member13with a coaxial dual-lumen configuration.FIG.5differs from the previous dual-lumen configuration shown inFIG.4, in that the inflation lumen26of the catheter shaft15is coaxially formed around the guide wire lumen25, and extends distally beyond the proximal end of the inflatable member13to its distal end or tip12. Further, one or more waist portion45of the at least two or more lobes32,34is attached to the wall of the catheter shaft15, and additional openings48,49situated in the first, or most proximal lobe34, and additional openings46,47situated in the second or most distal lobe32individually extend the inflation lumen26into each fluid-tight space present between the inner surface of each lobe and outer surface of the catheter shaft. Thereby, the inflatable member13including the at least two lobes32,34is in fluid communication with the inflation port18via the inflation lumen26. The coaxial dual-lumen configuration ofFIG.5can be particularly advantageous over a parallel arrangement, when an individual inflation/deflation of each lobe is desired, or when additional lumens for separately administering therapeutic and diagnostic liquids are needed.

For comparative purposes,FIG.6illustrates an alternative implementation of a parallel dual-lumen configuration that is similar to the dual-lumen configuration shown inFIG.4. However, the dual-lumen configuration differs in that the inflation lumen26extends distally beyond the proximal end of the inflatable member13to the distal end or catheter tip12, and one or more waist portion45of the at least two or more lobes32,34is attached to the wall of the catheter shaft15. The catheter shaft further includes at least two openings46,48that individually extend from the inflation lumen26through the wall of the catheter shaft15into each fluid-tight space present between the inner surface of each lobe32,34and the outer surface of the catheter shaft. Thereby, the inflatable member13including the at least two lobes32,34is in fluid communication with the inflation port18via the inflation lumen26. The parallel dual-lumen configuration ofFIG.6can be particularly advantageous over the dual-lumen configuration shown in FIG.4, when an individual inflation/deflation of each lobe is desired, or when an increased stiffness of the inflatable member13is needed.

FIG.7provides an alternative implementation of a coaxial triple-lumen configuration that is similar to the coaxial dual-lumen configuration shown inFIG.5. InFIG.7, however, the triple lumen configuration comprises a central guide wire lumen25, an inflation lumen26, and an additional drug perfusion lumen51, wherein the inflation and drug perfusion lumen are separate lumens that are not in fluid communication with each other, and coaxially formed around the guide wire lumen. An additional insert beneath lobe32shows a vertical, dashed line at a position ‘A’ along a length of the elongated member15, and a corresponding vertical cross-section ‘A-A’ that further illustrates the coaxial triple-lumen configuration. As evidenced from the horizontal and vertical cross-sections, the drug perfusion lumen51extends from a drug perfusion port located at the manifold17(not shown) into a drug release opening50located in the waist portion77of the at least two lobes32,34of the inflatable member13. Thereby, the triple lumen configuration enables the inflation/deflation of the at least two lobes32,34and the perfusion of therapeutic and diagnostic liquids, or agents, into the waist portion45/77at substantially the same, similar or different stages of the treatment procedure. For example, prior to administering treatment to a desired target area, the lobes32,34of the inflatable member13can be inflated to prevent blood flow through the target area, so as to prevent the inadvertent release of therapeutic liquids into the blood stream of the patient, followed by the targeted delivery of therapeutic liquids into the waist portion45/77that is located in the target treatment area. After a desired therapeutic treatment time window has elapsed, residual therapeutic agents can be withdrawn into the drug perfusion lumen51, and the lobes32,34of the inflatable member13deflated to restore blood flow to the target treatment area. In the implementation ofFIG.7, the waist portions45,77are shown adhered to the catheter shaft15, however, the waist portions can also be provided non-adhered (44,77), adhered (45), or partially adhered to the shaft (44,45), as exemplarily illustrated inFIG.4. In an alternate implementation, the inflation lumen26can simultaneously be a drug perfusion lumen, and the inflation port18can simultaneously be a drug perfusion port. In additional implementations, individual coaxial lumens can be adhered, partially adhered or non-adhered to each other along a length of the lumen. Such means may serve to reinforce or stabilize a position of one or more of the coaxial lumens with respect to the elongated member. For example, the coaxial lumen configuration can include stabilization welds, preferably along a proximal lumen portion of the elongated member. In addition, the various openings and ports at the elongated member and/or waist portion used for exchanging guidewires, and for transferring of therapeutic and diagnostic liquids, and/or gases can be provided structurally reinforced.

Summarizing the aforementioned constructional aspects and features of the balloon catheter in accordance to the present disclosure, the balloon catheter10at least comprises:an elongated member15having a proximal end19, a distal end12, and at least one lumen25,26extending at least partially through the elongated member; andan inflatable member13affixed to the elongated member adjacent to the distal end and in fluid communication with the at least one lumen26, the inflatable member having a radius R (42) and including at least two lobes32,34, the at least two lobes separated from each other by one or more waist portion44,45;wherein in an unpressurized state, the at least two lobes32,34of the inflatable member13are provided each folded and pleated, such that subsequent pressurization of the inflatable member individually unfolds each of the two or more lobes.

Further, the balloon catheter10comprises:a catheter tip12;a kink-protection sleeve16; anda manifold19.

In addition, the manifold19of the balloon catheter10comprises:an inflation port18; anda guide-wire port19,27-28.

Further, the elongated member15of the balloon catheter10comprises:an inflation lumen26, anda guide-wire lumen25, the guidewire lumen extending at least partially through the elongated member (27).

In the above, the guide wire lumen25of the elongated member15of the balloon catheter10connects the catheter tip12to the guide-wire port19,28, and the inflation lumen26is in fluid communication with the inflatable member13.

In one implementation, the inflation lumen26simultaneously is a drug perfusion lumen, and the inflation port18simultaneously is a drug perfusion port.

Based on the foregoing, the elongated member15of the balloon catheter10is configured as a dual-lumen shaft and a dual-lumen configuration of the elongated member is selected from a group consisting of a parallel arrangement, a coaxial arrangement and a combination of coaxial and parallel arrangements.

In an alternate implementation, the manifold19of the balloon catheter10further comprises a drug perfusion port, and the elongated member15further comprises a drug perfusion lumen51. In the alternate and the preceding implementation, the one or more waist portion77of the inflatable member13comprises at least one drug release opening50, wherein the at least one drug release opening50is in fluid communication with a drug perfusion lumen26,51within the elongated member15.

In the alternate implementation, the elongated member15is configured as a triple-lumen shaft and a triple-lumen configuration of the elongated member is selected from a group consisting of a parallel arrangement, a coaxial arrangement and a combination of coaxial and parallel arrangements.

Structural Reinforcement Elements

FIGS.8-10provide additional alternative implementations of the inflatable member13in accordance to the present disclosure. InFIG.8, the inflatable member13is based on the dual-lumen configuration shown previously inFIG.4, and includes at least two or more lobes32,34and one or more waist portions44,45. However, in comparison toFIG.4, the one or more waist portions44,45are not partially or fully adhered to the catheter shaft15, and include one or more additional structural element52that is disposed within the waist portions44,45, respectively. In reference toFIG.4, the one or more structural element52is configured to retain the lower base(s) of the one or more waist portions44,45, such that when the inflatable member13is pressurized, the waist portions44,45are retained at a pre-determined depth41relative to a rotational axis of the inflatable member13. The depth of the lower base is defined by a diameter of the structural element52, whereas the at least two lobes32,34of the inflatable member are free to expand to a diameter43, as exemplarily referenced inFIG.4. The one or more structural element52thereby reinforces at least one or more lower base(s) of the one or more waist portions44,45, and aids in stabilizing the inflatable member13such, that when the inflatable member13is pressurized, the axial stability or compliance of the inflatable member is further improved, particularly in the case when the one or more waist portions44,45are not adhered to the catheter shaft15. In this example, the one or more structural element52therefore aids in securing a waist portion to an inflatable member13and/or the catheter shaft15. Additional reinforcement of the one or more lower base(s) of the one or more waist portions44,45through attachment to the catheter shaft15, or provision of additional one or more structural element(s)52disposed in the one or more waist portions44,45of the inflatable member13can be particularly advantageous when an additional axial and radial stabilization or compliance of the inflatable member is desired, or radial expansion of the waist portion needs to be suppressed.

In further implementations, the one or more structural member52can be provided fixedly attached to an outer surface of the inflatable member13or disposed between multiple layers that in turn form a wall or outer surface of the inflatable member13. It is also contemplated that the structural member52can be provided not fixedly attached to the inflatable member, instead the structural member52is disposed within the waist portion44,45, wherein a geometrical shape of the inflatable member fixates the position of the structural member52within the waist portions44,45. The structural element52that serves as a means for reinforcement of the at least one of the one or more waist portions is selected from a group consisting of a fiber, a seam, a thread, a ring, a tubing, an adhesive, a crosslinked polymer, a point-like, a line-like, a helical, a circular, a cylindrical, a semi-circular, an arced, layered or interwoven attachment to the elongated member and combinations formed therefrom. Further, the structural element52can be provided in the form of a rigid, ductile, elastic, and/or spring-like material, and the material additionally be provided in the form of a solid, semi-solid, mesh-like or porous material, and/or suitable combinations selected therefrom. Materials preferably suitable for use as a structural element include those constructed of a material having a mechanical strength equal to or higher than that of the material(s) of which the inflatable member is formed from, for example the structural element may be constructed of a thermoplastic or thermoset polymer, a non-crosslinked or crosslinked polymer, an adhesive, ceramics, radiopaque materials and material compositions, and metals including stainless steel, nitinol, cobalt chromium or the same or similar biocompatible materials. In one preferred example, the structural element is made of the same material the balloon is formed from. In this case, the structural element can be either integrally formed with the balloon during the manufacture of the balloon or the structural element may be directly attached to the balloon using adhesive attachment mechanisms, chemical attachment mechanisms or other physical attachment processes such as laser welding, ultrasound welding, friction welding, plasma welding, thermal bonding, thermal forming or any suitable combination formed therefrom. In another example of the present disclosure, the structural element30is integrally formed by photo-crosslinking of the balloon material at the desired location(s) of the structural element(s)52. In a further example, the balloon is formed of a multilayer material and the structural element52is disposed between several layers of the balloon during manufacture. Preferably, the structural element52is a cylindrical portion of a heat-shrinkable tubing material which is placed over the balloon body and heat treated until mechanical and/or dimensional stability is reached. In general, the structural element52is one of a fiber, a seam, a thread, a ring, a tubing, an adhesive, a polymer, a point-like, a line-like, a helical, a circular, a cylindrical, a semi-circular, an arced, layered or interwoven attachment, preferably with a constant width and thickness. Preferably, the structural element has a varying width over its circumference, in other words, the structural element is asymmetric.

For further illustration,FIGS.9-10provide several alternative implementations of an inflatable member in accordance to the present disclosure. In these examples, the inflatable member13further comprises one or more structural elements disposed in the one or more waist portions of the at least two or more lobes. InFIG.9, the inflatable member comprises a series of six lobes53,54,55,56,57and58, that are equidistantly spaced apart by a series of five waist portions, each reinforced with an asymmetric structural element59. The structural elements of this example are formed from a series of shrink tubing, each cut to an isosceles trapezoid form. These asymmetric shrink tubing pieces are then placed over each waist portion of the inflatable member13, and heat-shrunk to form an inflatable member in accordance to the present disclosure, as shown. In this example, the asymmetric structural elements are arranged in the same orientation along the length of the inflatable member. Thereby, upon pressurization, the unidirectional orientation and arrangement of the asymmetric structured elements leads to a continuously curved shape of the inflatable member that facilitates enhanced bending modes, if so desired. It is further contemplated, that the above example is not limited to the exact disposition of the structural element, for example, instead of shrink tubing any other of the aforementioned structural elements can be equivalently implemented in an asymmetric form.

In comparison,FIG.10illustrates an inflatable member comprising a series of four lobes53,54,55, and56that are equidistantly spaced apart by a series of three waist portions, each reinforced with an asymmetric structural element60. InFIG.10, however, the asymmetric structural elements60are alternatingly arranged, reversing their orientation every other element along the length of the inflatable member. Thereby, upon pressurization, the bi-directional orientation of the asymmetric structural elements leads to a meandering/undulating shape of the inflatable member that facilitates enhanced bending modes, if so desired. Alternative implementations include placing asymmetric structural elements in a spiraling or helical orientation along the length of the inflatable member, or other specific arrangements and orientations that in turn facilitate other suitable bending modes of the inflatable member, as desired for a specific use. Such reinforced inflatable members of the present disclosure can be suitable for facilitating an enhanced adaption of the inflated balloon portion to the natural vessel anatomy, and may further prevent undesired straightening and distension of a diseased vessel portion.

By providing an inflatable member in accordance to the present disclosure, additional bending modes of the inflatable member are enabled, that further enhance 3D plaque modulation of a lesion. Thereby, the angioplasty balloon catheter can suitably exhibit an even more enhanced, directional capability to controllably inflate in the obstructed or diseased vessel portion, wherein the application of focalized pressure to the lesion results in a controllable fracture of the lesion at preferably multiple locations, which in turn facilitates an efficient and selective modulation, modification, and/or fracture of target lesions at substantially lower pressure ranges compared to conventional angioplasty catheters. As a result, trauma can be reduced and a safe and clinically more effective treatment of the patient can be performed.

Summarizing the above constructional aspects and features of the balloon catheter10in accordance to the present disclosure, the one or more waist portion44,45of the balloon catheter10can include one or more structural element52. In turn, the one or more structural element52reinforces at least one or more of the one or more waist portions44,45. In the various implementations, the one or more structural element52of the balloon catheter10serves as a means for reinforcement of at least one of the one or more waist portions44,45and is selected from a group consisting of a fiber, a seam, a thread, a ring, a tubing, an adhesive, a crosslinked polymer, a point-like, a line-like, a helical, a circular, a cylindrical, a semi-circular, an arced, a layered, and a interwoven attachment to the elongated member and combinations formed therefrom. Further, the one or more structural element52of the balloon catheter10is preferably asymmetric, and can be arranged in a unidirectional orientation relative to a length axis of the inflatable member13, in a bidirectional orientation relative to a length axis of the inflatable member13and/or arranged in an alternating combination of unidirectional and bidirectional orientation relative to a length axis of the inflatable member13.

Manufacturing Aspects

Concerning the general construction aspects of the angioplasty catheter system of the present disclosure, the catheter components can be manufactured from biocompatible, polymeric, metallic and ceramic materials. For example, the catheter components, including the inflatable member, can be manufactured from aliphatic, semi-aromatic and aromatic polyamides (PA); polyether ether ketones (PEEK); polyethers; polyimides (PI); linear and nonlinear, branched or non-branched, low molecular weight, medium molecular weight, or high molecular weight; low density, medium density, or high density polyolefins, including polyethylene (PE, LD-PE, HD-PE) and polypropylene (PP), silicones, thermoplastic elastomers, such as polyurethanes (TPEs) and fluoroelastomers, for example FEP or PTFE, polycarbonates (PC), polyesters such as polyethylene terephthalate (PET) and combinations, including blends and copolymers of any of these materials, such as polyether block amides (PEBA), for example.

Further, the catheter components, including the inflatable member, can be fabricated in a single layer, dual-layer, or in multi-layer configuration. In the instance of dual-layer or multi-layer configurations, certain catheter elements, including for example the shaft or the inflatable member, may utilize the same material for each layer or may utilize different materials for each layer. The multiple layers may be glued, melted or fused together with or without an adhesive, or by employing a co-extrusion or welding process. Alternatively, the multiple layers are not required to be attached, glued or welded together; instead, the multiple layers may be allowed to move independently. Additionally, the elastic modulus, durometer or hardness of the materials selected for each layer or component of the catheter system can be varied to beneficially alter the performance aspects of the individual catheter components.

In addition, the chemical functionality and/or physical polarity of the catheter materials can be changed to enhance interfacial adhesion between the differing layers and/or to provide surfaces and/or inner lumen with an increased lubriciousness or changed surface energy when in contact with guide wires, therapeutic and diagnostic liquids, or functional coatings, for example. These chemical and physical treatments or alternations may include for instance chemical additives that can introduce another chemical functionality to the interfacial surface, when added to an exemplary base polymer formulation intended to form one or more layers of the catheter component, for example, including functional groups such as carboxy- and/or amino groups, which can effectively enhance the underlying polarity of the layer and the substrate, thus facilitating enhanced adhesion and mechanical fixation strength in between one or more layered structures of catheter components.

Other surface modifications, such as coatings and/or plasma techniques can be employed for further changing the chemical and/or the mechanical properties of the materials, layers or components of the angioplasty catheter system, wherein the modification of the catheter materials may affect the polarity, surface energy and/or friction coefficient of layers and/or surfaces of the catheter components. Still, other suitable techniques may incorporate additives, adhesives and/or filling agents, which can introduce other beneficial properties to the catheter materials. For example, the components of the catheter system may incorporate radiopaque elements embedded within polymeric materials to selectively increase fluoroscopic visibility at desired locations. Alternatively, or supplementary, the components of the catheter system may incorporate dyes or pigments at select locations to provide visible color-indications to a treatment provider. Additionally, the shaft may incorporate fluoropolymer-based filler particles/fibers to permanently decrease the frictional coefficient as compared to an untreated base-polymer formulation or activatable, single-use coatings. Furthermore, the catheter components, including the shaft and inflatable member can be provided reinforced and may contain metal or polymer-based strands, fibers, wires, braids, meshes and/or fabrics embedded as layers, sections or regions into the base-material.

Concerning the constructional characteristics of the inflatable member, the materials utilized in the construction can be selected, configured and formulated such, that the balloon responds in specific ways to the application of external pressure. By way of construction, the elongated tubular member responds to the application of pressure by two distinct growth mechanisms, namely by a change of axial length and radial diameter. This characteristic change of the balloons' dimensional characteristics during application of pressure is generally referred to as dimensional compliance. Particularly with respect to the target vessel diameter of the treated lesion, the radial compliance, often termed ‘balloon compliance’ as listed on the product label (or recorded as ‘compliance curve’), describes the way of which the diameter of the balloon is going to respond to the application of pressure. The change in axial (longitudinal) dimensions is accordingly referred to as axial compliance. By choice of materials, the dilation elements or balloons can be embodied as compliant balloons, semi-compliant and non-compliant balloons. Compliant medical balloons may expand by 100% or greater upon inflation. Non-compliant dilation balloons expand very little, if at all (<7%), when pressurized from a nominal diameter to a rated burst pressure. Semi-compliant balloons exhibit a moderate degree of expansion (≥7-12%), when pressurized from its nominal or operating pressure (e.g. the pressure at which the balloon reaches its nominal diameter) to its rated burst pressure (e.g. the undesirable pressure threshold at which the balloon can be subject to rupture or burst). Other than by choice of materials and constructional aspects, the desired compliance characteristics of the inflatable member can favorably be controlled through the manufacturing process.

The inflatable members of the present disclosure can be manufactured using known manufacturing methods such as balloon blowing, blow molding, thermoforming, dip molding, or any other manufacturing methods suitable for the manufacture of balloons. It shall be understood to one of ordinary skill in the art that conventional balloon manufacturing techniques can be utilized within the manufacture of balloons of the present disclosure. For example, the materials of the balloon may be subjected to mechanical processes before, during or after the manufacture of the balloon. For instance, when a blowing process is utilized for the manufacturing process, the tubular member from which the balloon is to be formed can be stretched before, during or after the blowing process. Yet still, the temperature as well as the inflation pressure or other parameters can be changed during the manufacturing process to affect the properties of the manufactured balloon.

For further illustration,FIG.11AandFIG.11B provide cross-sectional views of a waist portion of the inflatable member manufactured by balloon blowing and/or thermoforming in accordance with the present disclosure. InFIG.11A, characteristic wall thickness proportions of an inflatable member manufactured by a single stage balloon blowing process are shown. The inflatable member includes a proximal and a distal end, each having a first wall thickness61, at least two or more lobes32,34, each having a second wall thickness62, and one or more waist portions44, each having a third wall thickness63. InFIG.11AandFIG.11B, the first wall thickness61is exemplarily determined as the average of one or more wall thickness at the proximal and distal end (neck/cone) of the inflatable member13. The second wall thickness62is exemplarily determined as the average of one or more (mantle) wall thickness across the lengths36, and38of the at least two lobes32,34, and the third wall thickness63is determined as the average of one or more wall thickness across the waist portion length37of the one or more waist portions44,45, respectively. As a result of the single stage balloon blowing process, the first wall thickness61exceeds the second wall thickness62, and the third wall thickness63exceeds the second wall thickness62. Thereby, application of a single stage balloon blowing process results in an inflatable member, wherein the wall thickness63at the waist portion44is typically higher than the wall thickness62of the at least two or more lobes32,34of the inflatable member. This particular single stage manufacturing process can therefore be advantageous for such situations, where a reinforced waist portion with decreased flexibility is desired. The decreased flexibility at the waist portion is particular beneficial in reducing an amount of axial load that is transferred between the inflatable member and an area to be treated65,66.

Preferably, however, it can be desired that the inflatable member of the present disclosure exhibits a third wall thickness63at the one or more waist portions44, that does not exceed the second wall thickness62at the least two or more lobes32,34. The inventors of the current disclosure have found that the above feature can be achieved by combining a balloon blowing process with a consecutive thermoforming process. For further illustration,FIG.11Bprovides characteristic wall thickness proportions of an inflatable member manufactured by a two stage process consisting of a first stage balloon blowing and second stage thermoforming process. InFIG.11B, the inflatable member includes a proximal and a distal end, each having a first wall thickness61, at least two or more lobes32,34, each having a second wall thickness62, and one or more waist portions44, each having a third wall thickness63. As a result of performing a first stage balloon blowing and a second stage thermoforming process, the first wall thickness61exceeds the second wall thickness62, and second wall thickness62exceeds the third wall thickness63. Thereby, application of a two stage process consisting of a first stage balloon blowing and second stage thermoforming process results in an inflatable member, wherein the wall thickness63at the waist portion44is thinner than the wall thickness62of the at least two or more lobes32,34of the inflatable member. This particular two-stage manufacturing process can be advantageous for such situations, where a thinned out waist portion44with increased flexibility is desired. The increased flexibility at the waist portion is particular beneficial in enhancing a magnitude of variable directional forces70,73conveyed onto a portion66of the area to be treated. These particular effects will further be described in reference toFIGS.12-13, andFIGS.17-18.

In additional implementations, a flexibility at the one or more waist portions of the at least two or more lobes can be varied, for example provided as a set of increased and decreased flexibilities, which, when combined, result in a favorable combination of improved axial stability and increase of the magnitude of variable directional forces created at the waist portions.

Summarizing the additional constructional aspects and features of the balloon catheter according to the disclosure, the inflatable member13of the balloon catheter10further includes:a proximal and a distal end, each having a first wall thickness61;at least two lobes32,34, each having a second wall thickness62, andone or more waist portions44,45, each having a third wall thickness63.

In one implementation, the first wall thickness61of the inflatable member of the balloon catheter10exceeds the second wall thickness62, and the second wall thickness exceeds the third wall thickness63, thereby increasing flexibility at the one or more waist portion44,45, and enhancing a magnitude of variable directional forces70,73conveyed onto a portion66of the area to be treated65.

In another implementation, the first wall thickness61of the inflatable member exceeds the second wall thickness62, and the third wall thickness63exceeds the second wall thickness, thereby decreasing flexibility at the one or more waist portion44,45, and reducing an amount of axial load that is transferred between the inflatable member and an area to be treated (65,66).

The inflatable members shown and described with regard toFIGS.1-11have been designed to be utilized to perform angioplasty procedures in accordance to the present disclosure. Unlike conventional angioplasty catheters comprising single-membered angioplasty balloons, the angioplasty catheters of the current disclosure comprise an elongated member having a proximal end, a distal end, and at least one lumen extending at least partially through the elongated member; and an inflatable member proximally affixed to the elongated member adjacent to the distal end and in fluid communication with the at least one lumen, the inflatable member having a radius R and including at least two lobes, the at least two lobes separated from each other by one or more waist portion, wherein in an unpressurized state, the at least two lobes of the inflatable member are provided each folded and pleated, such that subsequent pressurization of the inflatable member individually unfolds each of the two or more lobes. Through provision of an inflatable member according to the criteria set forth above and below, the inflatable members of the present disclosure can provide a novel combination of a concerted radial expansion and simultaneous longitudinal bending mode, that enables delivering focalized pressure to a lesion, and thereby, resulting in a controllable fracture of the lesion at preferably multiple locations. Because the inflatable member of the current disclosure can be utilized at comparatively lower pressures compared to conventional angioplasty balloons, a substantially atraumatic, three dimensional plaque modulation is achieved. For further illustration, the specific technical effects are next described with reference toFIGS.12-20.

FIG.12is a graphical representation of lesion-fracturing effects observed when applying an inflatable member of the present disclosure to a calcified lesion. InFIG.12, an inflatable member comprising at least two lobes32,34, and one or more waist portions44are depicted. The inflatable member is shown in contact to a lesion66that is situated in a blood vessel65. In reference toFIG.4, upon pressurization of the inflatable member13, the position (of the lower base) of the waist portion44is shifted to a second position44′ and the inflatable member pushed into the lesion. In the pressurized state, the at least two or more lobes32,34of the inflatable member13controllably convey opposing axial and equidirectional radial loads or forces between the lobes and an area to be treated (65,66), resulting in a specific stress distribution profile that is indicated as a dash-dotted line inFIG.12. The stress distribution along the mantle surface of the inflatable member changes from a maximum radial stress state directly above the at least two or more lobes32,34to a radial stress relief zone directly above the waist portion44. As a result, variable directional forces, indicated by black arrows, are created through concerted interaction between the axial and radial force components present at the waist portion. In turn, these directional forces are projected onto a portion66of the area to be treated65that is situated around the waist portion44. The directional forces create additional cleavage planes67,68that favorably fracture the lesion66. In other words, because the variable directional forces conveyed between the lobes and around the waist portion differ from the radial forces conveyed by the lobe portions of the inflatable member and an remainder of the area to be treated, a variable pressure differential is induced between the lobes and waist portion of the inflatable member that, when conveyed to an area to be treated, results in the preferential formation of lesion fractures around the waist portion of the inflatable member. The directional forces are variable in magnitude and direction depending on the pressurization state of the inflatable member. Due to the concerted action of radial expansion, and simultaneous longitudinal bending, focalized pressure is delivered to the lesion, and thereby, results in a controllable fracture of the lesion at multiple locations situated around the waist portion. In other words, a segmentation of the inflatable member at the at least two or more lobes induces a ‘pressure interference’ that results from the combination or overlay of the axial and radial force components at the waist portion of the inflatable member in a pressurized state. In turn, stress inflection points are controllably formed, that induce a ‘segmental inflection’ of the lesion, enabling pressure to be directionally projected into the lesion and away from the vessel wall, and thereby, facilitating an atraumatic and controlled lesion cracking.

FIG.13illustrates a cross-lateral view of dimensional relationships of an inflatable member of the present disclosure characterizing a controlled direction of forces at different pressurization regimes, in accordance with the present disclosure. InFIG.13, the outline of an inflatable member comprising at least two lobes32,34, and one or more waist portions44is depicted at a lower pressurization regime that is indicated as a black, continuous line, and at a higher pressurization regime that is depicted as a dashed line. The rotational axis of the inflatable member in turn is indicated as a dash-dotted line. Application of pressure, from an unpressurized or lower pressurization state to a pressurized or higher pressurization state, shifts the upper base of the waist portion44from a distance or depth40relative to the lower base of the waist portion44to a depth40′, and shifts the lower base from a distance or depth41above the rotational axis of the inflatable member to a depth41′. Further, the lengths of the upper base37and the lower base33are compressed to the lengths37′ and33′; and an angle76that is formed between the legs91,92of the upper and lower base is changed to angle76′ upon pressurization. Application of pressure, from an unpressurized or lower pressurization state to a pressurized or higher pressurization state, changes the direction and magnitude of the directional force70(resulting from the vectorial addition of radial force component71, and axial force component72) and directional force73(resulting from the vectorial addition of radial force component74, and axial force component75) so that new directional forces70′ and73′ result. As becomes apparent from the change of magnitude and direction of the variable directional forces70, and73, upon pressurization, radial stress around the waist portion is directed away from the vessel wall and focalized into the lesion at an angle about perpendicular to the legs91,92of the upper and lower base of the waist portion44. As a specific effect of the variable directional forces conveyed between the lobes, waist portion and lesion, at different stages of pressurization, fracture planes are created along the direction of the directional forces that result in a controllable fracture of the lesion at multiple locations67,68situated around the waist portion44. At the same time concentrated radial stress is directed away from the vessel wall65. The inventors now have found, that the above described effect of lesion fracture around the waist portion of the inflatable member can be maximized, when the waist portion44of the inflatable member has a length37(L) not greater than two times the radius42(R) of the inflatable member. In addition, the inventors have found, that decreasing or increasing, respectively changing the wall thickness63at the waist portion44in relation to the wall thickness62of the at least two or more lobes32,34of the inflatable member changes a magnitude and direction of the variable directional forces70, and73in a pressurized state. For example, decreased wall thickness63results in enhancing a magnitude of variable directional forces70,73conveyed onto a portion66of the area to be treated65and further, results in a decrease of the angle76formed between the legs91,92, thereby increasing a corresponding incident angle that exists between the directional forces70,73. This surprisingly infers that the change of wall thickness63allows for controlling the angle at which the variable directional forces are focalized into the lesion, and thereby provides for an additional means to reliably control the depth, direction, location and number of lesion fractures. For further illustration, the specific technical effect of the segmentation of the inflatable member into the at least two or more lobes via one or more waist portions will be further described with reference toFIGS.14-19.

FIGS.14A-14Dare stress distribution diagrams resulting from forces applied to an obstructed vessel portion utilizing an inflatable member with variable waist portion lengths, in accordance with the present disclosure.FIG.14Ais a graphical representation of forces applied to a calcified lesion66by a single-membered, standard angioplasty balloon13. The graphical representation shows the cross section of an angioplasty balloon13, and the calcified lesion66with stress zones denoted in van Mises stress (MPa) over unit lengths (see legend). As shown inFIG.14A, the conventional angioplasty balloon provides a generally uniform force to the lesion along its entire length. Because the stress is homogenously distributed, and because there is an absence of stress concentrator sites, conventional angioplasty catheters require the use of comparably high pressures to fracture a lesion. Further, these limitations contribute to a lack of uniform lesion fracture, such that the depth, direction, location and number of the lesion fracture(s) cannot be reliably controlled and/or an adequate patency of the vessel cannot be reliably achieved.

FIGS.14B to14D, are graphical representations of forces applied to a lesion utilizing an inflatable member design ofFIGS.2-8. Accordingly, in the provided examples, the inflatable member13includes at least two or more lobes32,34and one or more waist portions44. InFIGS.14B,14C and14D, the waist portion length37of the inflatable member is varied from 2, 4 and 6 mm, as indicated by dashed lines, whereas the lengths of lobes36,38each remain identical at 20 mm, and the diameter43of the inflatable member each remains identical at 6 mm. As can be observed from the stress distribution profiles generated around the waist portion, the change of stress intensity resulting from the overlay of directional forces, is dependent on the waist length, and is maximized when the waist portion44of the inflatable member has a length37(L) not greater than two times the radius42(R) of the inflatable member. Because the variable directional forces conveyed between the lobes and around the waist portion differ from the radial forces conveyed by the lobe portions of the inflatable member and a remainder of the area to be treated, radial stress is directed away from the vessel wall above the waist portion. The stress intensity around the waist portion is therefore lower than that of a conventional angioplasty balloon. Further, because a stress gradient is induced between the lobes and waist portion of the inflatable member, stress concentrator sites or inflection points are generated, that in turn result in the preferential formation of lesion fractures around the waist portion of the inflatable member, in analogy to the description provided inFIG.13.

FIGS.15A-15Dare stress distribution diagrams resulting from different magnitudes of forces applied to an obstructed vessel portion utilizing an inflatable member in accordance with the present disclosure. InFIGS.15A-15D, the inflatable member13includes at least two or more lobes32,34and one or more waist portions44. In the provided example, the waist length37is 4 mm, the lengths of lobes36,38are 20 mm, and the diameter43of the inflatable member is 6 mm. InFIGS.15A-15D, forces applied to the lesion66at different inflation pressures are varied from between 15 to 60 N, in 15 N increments each. As can be observed from the stress distribution profiles generated around the waist portion, the change of stress intensity resulting from the overlay of directional forces is dependent on the inflation pressure or force applied to the lesion. Because the variable directional forces conveyed between the lobes and around the waist portion differ from the radial forces conveyed by the lobe portions of the inflatable member and a remainder of the area to be treated, radial stress is directed away from the vessel wall. The radial stress intensity around the waist portion is therefore lower than that of a conventional angioplasty balloon. Further, because a stress gradient is induced between the lobes and waist portion of the inflatable member, stress concentrator sites or inflection points are generated, that in turn result in the preferential formation of lesion fractures around the waist portion of the inflatable member, in analogy to the description provided inFIGS.13-14.

FIGS.16A-16Dare polariscope images illustrating the stress distribution in a lesion resulting from different amounts of pressurization of the inflatable member in accordance with the present disclosure. In each of theFIGS.16A-16D, an inflatable member13includes at least two or more lobes32,34, and one or more waist portions44. In the provided examples, the waist length37of the inflatable member is 3 mm each, and the diameter at nominal pressure (16 bar) is 3 mm each, whereas the lengths of lobes36,38are each 80 mm. From left to right, in each of theFIGS.16. A-16D, the inflatable member is in direct contact with a model lesion66, and held in a pressurization state of 4, 6, 8 and 12 bar of pressure. A principal stress line78is observed in each of the images as a dark isochromatic line that incrementally bends away from the vessel wall and into the model lesion, at increasing inclinations, as the pressure is incrementally increased in 2 bar steps. The principal stress lines78are oriented in the same direction as the direction of the cleavage planes67,68, as exemplarily referenced inFIG.12. In turn, stress concentrator sites, or stress inflection points are controllably generated at the waist portion44, visible as an alternation of regions of dark and light contrast, that in turn favorably fracture the lesion66, as desired. In the provided example, when the pressure is increased, the principal stress lines bend away from the vessel wall and into the lesion at angles that correspond to the angles76,76′ ofFIG.12. Hence, as a specific technical effect of the segmentation of the inflatable member into the at least two or more lobes via one or more waist portions, variable directional forces are created, that when conveyed between the lobes, waist portion and lesion, at different stages of pressurization, create cleavage planes along the direction of the variable directional forces, that in turn result in a controllable fracture of the lesion at multiple locations situated around the waist portion.

FIGS.17A-17DandFIGS.18A-18Dare polariscope images illustrating the stress distribution in a lesion resulting from different amounts of pressurization of inflatable members manufactured by balloon blowing, and balloon blowing and thermoforming, respectively, in accordance with the present disclosure. InFIGS.17A-17D, the inflatable member has been manufactured by a single-stage balloon blowing process. In the example ofFIG.17A-17D, when the inflatable member is manufactured by a single-stage balloon blowing process, a second wall thickness (62) exemplarily ranges from about 0.020-0.025 mm, and a third wall thickness (63) exemplarily ranges from about 0.025-0.050 mm. Thereby, in reference toFIG.11A, the first wall thickness (61) of the inflatable member exceeds the second wall thickness (62), and the third wall thickness (63) exceeds the second wall thickness (62). In comparison, inFIGS.18A-18D, the inflatable member has been manufactured by a first-stage balloon blowing process and a second stage thermoforming process. Thereby, in reference toFIG.11B, the first wall thickness (61) exceeds the second wall thickness (62), and the second wall thickness exceeds the third wall thickness (63).

In each of theFIGS.17A-17DandFIGS.18A-18D, an inflatable member13includes at least two or more lobes32,34, and one or more waist portions44. In the provided examples, the waist (or lower base) length37of the inflatable member is 1 mm each, and the diameter at nominal pressure (16 bar) is 3 mm each, whereas the lengths of lobes36,38are each 20 mm. From left to right, in each of theFIGS.17A-17DandFIGS.18A-18D, the inflatable member is in direct contact with a model lesion66, and held in a pressurization state of 4 bar (A), 6 bar (B), 8 bar (C) and 12 bar (D) of pressure. A principal stress line78is observed in each of the images as a dark isochromatic line or fringe that incrementally bends away from the vessel wall and into the model lesion, at increasing inclinations, as the pressure is incrementally increased in 2 bar steps. As can be observed from the direct comparison ofFIG.17A-17DwithFIG.18A-18D, in the case of inflatable members manufactured by a first-stage balloon blowing process and a second stage thermoforming process, additional principal stress lines or fringes are present at equal amounts of pressurization (FIG.18D). This indicates, that at equal amounts of pressurization, the stress distribution profiles for the inflatable members produced by the two different manufacturing processes are different, and further, that a stress loading state when the first wall thickness (61) exceeds the second wall thickness (62), and the second wall thickness (62) exceeds the third wall thickness (63) is higher than a stress loading state, when the first wall thickness (61) exceeds the second wall thickness (62), and the third wall thickness (63) exceeds the second wall thickness. Thereby, a magnitude of variable directional forces70,73conveyed onto a portion66of the area to be treated65is enhanced. As a result, a change of the wall thickness63of the one or more waist portions44,45changes a magnitude and direction of the variable directional forces70, and73, such that the depth, direction, location and number of lesion fractures is reliably controlled.

In alternate implementations, and in reference toFIGS.11A-B, it is further contemplated, that one or more third wall thickness63of the one or more waist portions44,45of the at least two lobes32,34of the inflatable member10can be varied with respect to the first (61) and second wall thickness (62), such that when combined, can result in a favorable combination of improved axial stability and increase of the magnitude of variable directional forces created at the waist portions. For example, a balloon catheter10comprising an inflatable member13having a distal predilatation portion and a proximal dilatation portion can consist of a predilatation portion that is manufactured by a two-stage balloon blowing and thermoforming process, and a proximal dilatation portion manufactured by a single stage balloon blowing process. Thereby, the distal predilatation portion can exhibit a favorable increase of the magnitude of variable directional forces at the waist portions across the length of the distal predilatation portion, and the proximal dilatation portion can exhibit an improved axial stability across the length of the proximal dilatation portion.

FIGS.19A-19Dare polariscope images illustrating the stress distribution in a lesion resulting from a variation of the waist portion length at equal amounts of pressurization of the inflatable member in accordance with the present disclosure. InFIGS.19A-19D, an inflatable member13includes at least two or more lobes32,34, and one or more waist portions44. In the provided examples, the waist portion length37of the inflatable member is varied, from left to right, from 1 mm (A), 2 mm (B), 4 mm (C) and 6 mm (D). The diameter at nominal pressure (16 bar) is 3 mm each, whereas the lengths36,38of the lobes32,34are 20 mm each. In each of theFIGS.19A-19D, the inflatable member is in direct contact with a model lesion66, and held in a pressurization state of 8 bar of pressure. InFIGS.19A and19B, an overlapping or mutual principal stress line78, visible as a dark isochromatic line or fringe that incrementally bends away from the vessel wall and into the model lesion is formed between the adjacent lobes32,34of the inflatable member. InFIGS.19C and19D, such principal stress 78 line is absent. As a result, when the waist portion length L (37) does not exceed two times the radius R (42) of the inflatable member in a pressurized state, principal stress lines can optimally overlap or form between the at least two or more adjacent lobes32,34of the inflatable member, whereas, when the waist portion length exceeds two times the radius R (42) of the inflatable member, such concerted interaction is absent, or only present at higher, and thus less desired states of pressurization. Hence, when one or more of the waist portion44,45of the at least two lobes32,34of the inflatable member13comprises a length L (37) not greater than two times the radius R (42) in a pressurized state, stress inflection points are controllably induced, that [result in a pressure interference and segmential inflection and] result in the preferential formation of lesion fractures67,68at each waist portion44of the inflatable member, thereby maximizing the effect of lesion fracture around the waist portion of the inflatable member.

It has been further found by the inventors that an inflatable member comprising at least two or more lobes and one or more waist portions in accordance with the present disclosure is able to distribute and thereby reduce an amount of torsional load that is generated during unfolding of the at least two or more lobes that can be transmitted between the inflatable member, lesion and surrounding area of treatment, as compared to a conventional single-membered balloon. For further illustration,FIGS.20A-20Bprovide graphical representations of torsional loads applied to a treatment area by a conventional inflatable member (A) versus an inflatable member comprising at least two or more lobes (B) in accordance with the present disclosure. InFIGS.20A-20B, a partially folded and pleated inflatable member13is shown in contact to a lesion66located in a blood vessel65.FIG.17Acomprises a conventional, single inflatable member, whereasFIG.17Bdepicts an inflatable member comprising a distal, middle and proximal lobe and two waist portions according to the current disclosure. In each case, the distal end of the balloon is shown dimensionally constrained and held at a radius42in a partially inflated state, and the proximal end is held unconstrained by the blood vessel and in an inflated state having a radius42′. Further, pleat lines85, indicated as a long-dash line, are shown on the distal and proximal lobes, with each having a starting position79,81in an uninflated state, that when inflated, rotate by an unfolding angle83, and84, respectively.

However, when the two different types of inflatable members are inflated, inFIG.20A, inflation of the conventional, single membered angioplasty balloon creates a torsional load between the fix points79and82, across the entire length of the balloon, whereas inFIG.20Bthe distal lobe generates a torsional load between the fix points79, and83, and the proximal lobe creates a torsional load between the fix points81,82. As a result, inFIG.20B, because the length of individual lobes36of the inflatable member13of the present disclosure is reduced, the torque of the individual lobes is also reduced to the same extent. The total sum of the individual torques of the individual lobes cannot exceed the torque that would be otherwise generated over an entire length of a balloon. Therefore, the inflatable member comprising at least two or more lobes and one or more waist portions in accordance with the present disclosure is able to reduce an amount of torsional load that is generated during unfolding of the at least two or more lobes that can be transmitted between the inflatable member, lesion and surrounding area of treatment. In addition, the torsional load generated by each lobe is interrupted at each waist portion. As a result, the generation of torsional loads of an inflatable member of the current disclosure remains localized at the individual lobes, reducing potential damage that could occur from torsional loading over an entire length of a lesion, as would be the case if a single-membered balloon construction of the same length and diameter were to be used.

Based on the foregoing description, the balloon catheter10according to the current disclosure, comprising:an elongated member15having a proximal end19, a distal end12and at least one lumen25,26extending at least partially through the elongated member; andan inflatable member13affixed to the elongated member adjacent to the distal end and in fluid communication with the at least one lumen26, the inflatable member having a radius R (42) and including at least two lobes32,34, the at least two lobes separated from each other by one or more waist portion44,45;wherein in an unpressurized state, the at least two lobes32,34of the inflatable member13are provided each folded and pleated, such that subsequent pressurization of the inflatable member individually unfolds each of the two or more lobes;demonstrates that, in a pressurized state, a segmentation of the inflatable member into the at least two or more lobes:distributes, and thereby reduces a torsional load79,82that is transferred between the inflatable member and an area to be treated65,66;controllably conveys opposing axial forces72,75between the lobes (at the waist portion), and thereby reduces an amount of axial load that is transferred between the inflatable member and an area to be treated; andcontrollably conveys equidirectional radial71,74forces between the lobes32,34and around the waist portion44that differ in magnitude from the radial forces conveyed by the lobes, and thereby directs away radial stress from a vessel wall65around the waist portion44;characterized in that the combination of the opposing axial72,75and equidirectional radial71,74forces around the waist portion44create variable directional forces70,73that, when conveyed onto a portion66of the area to be treated65, controllably induce stress inflection points that [result in a pressure interference and segmential inflection and] result in the preferential formation of lesion fractures67,68at each waist portion44of the inflatable member.

In the above, the one or more waist portion44,45of the inflatable member13comprises one or more length L (37) selected from at least a set of ranges that includes 0-20 mm, 1-2 mm, 2-4 mm, 4-6 mm, 6-8 mm, 8-10 mm, 10-12 mm, 12-14 mm, 14-16 mm, 16-18 mm, and 18-20 mm. Preferably, the one or more waist portion44,45of the inflatable member13comprises a length L (37) not greater than two times the radius R (42) in a pressurized state, so as to controllably induce stress inflection points that [result in a pressure interference and segmential inflection and] result in the preferential formation of lesion fractures67,68at each waist portion44of the inflatable member.

Further, in a pressurized and lesion-contacting state, the waist portion between the at least two lobes of the inflatable member and an area to be treated65,66forms an impact zone that is substantially shaped as a trapezoid;wherein the trapezoid shape includes:an upper base having a first length37that is equivalent to the length of the waist portion;a lower base having a second length33smaller than the first length;a first depth equivalent to a radial distance40between the upper base and the lower base;a second depth equivalent to a radial distance41between the lower base and a rotation axis of the inflatable member;two legs91,92formed at an angle76that is defined by the (first and second) lengths37,33and radial distances40,41between the lower and upper base,
wherein a sum of the first and second depths40,41are equivalent to an outer radius42of the inflatable member, and wherein the first depth is equivalent to the depth of the waist portion.

Further, in the above, a change of the third wall thickness63of the one or more waist portions44,45changes a magnitude and direction of the variable directional forces70, and73, such that the depth, direction, location and number of lesion fractures is reliably controlled.

With respect to the preceding, a third wall thickness63at the waist portion44,45of the at least two lobes32,34of the inflatable member13of the balloon catheter10of the present disclosure can be varied with respect to the first and second wall thickness, such that at least one of the axial stability and a magnitude and direction of the variable directional forces70, and73is reliably controlled. In other words, the one or more third wall thickness63of the waist portion44,45of the at least two lobes32,34of the inflatable member13of the balloon catheter10of the present disclosure can consist of multiple, different wall thicknesses63, wherein the first wall thickness61of the inflatable member exceeds the second wall thickness62, and the second wall thickness exceeds the third wall thickness63, or wherein the first wall thickness61of the inflatable member exceeds the second wall thickness62, and the third wall thickness63exceeds the second wall thickness.

Static and Pulsatile Modes of Angioplasty Catheter Operation

Conventional modes of operation of current balloon catheters include inflation of the balloon using standard inflation devices. The balloons are manually inflated to a pressure regime between a nominal pressure and below rated burst pressure, held for short dwell time at a static (or constant) pressure, and subsequently, deflated and withdrawn from the patient. Given the limitations of current angioplasty balloon catheter systems and available angioplasty treatment procedures, it is therefore further contemplated, that the angioplasty catheter of the current disclosure is preferably operated with a pulsatile, and/or modulated pressure regime. The pulsatile pressure modulation is intended to enhance and/or facilitate fracture formation within the area of treatment by superimposing a dynamic pressure modulation onto the inflatable member during use. Pulsatile pressure modulation can afford additional benefits through additional generation of vibrational modes acting on the inflatable member and lesion. Depending on the shape of the inflatable member, and the underlying lesion geometry, specific modes can be generated in both inflatable member and lesion, thereby allowing the controlled formation of variable directional forces at the waist portion of the inflatable member and permitting the delivery of focalized pressure to complex lesions without having the limitations or drawbacks of the known angioplasty catheter systems and procedures. The static and pulsatile modes of operation will be next described with reference toFIGS.21-22.

For further illustration,FIG.21provides a perspective view of an angioplasty balloon catheter and adjunct devices for performing an angioplasty treatment in accordance with the present disclosure. InFIG.21, an angioplasty catheter system10is shown inserted into a support catheter400that in turn comprises a manifold88, a hemostatic valve89, a flushing port86, and a support catheter shaft87. The support catheter400can be used in conjunction with the balloon catheter10of the current disclosure to provide for additional substantial structural guidance and support as an external tubular shield that reduces potential vessel damage during transport and maneuvering operations. Further, the support catheter can provide length-adjustability to an inflatable member13of the balloon catheter10, if so desired. The inflatable member13of the angioplasty catheter extends beyond the distal edge of the support catheter shaft, and is routed over a guide wire11, that in turn extends from the tip of the angioplasty catheter balloon12to a guide wire port19. The inflation port18can be operationally coupled to a standard inflation device200, and operated by manual control, or preferably operationally coupled to a pressure generator300that is capable of generating a programmable, pulsatile pressure modulation, as described previously. Accordingly, the pressure generator300suitable for pulsatile pressure modulation may modulate one or more of a phase, an amplitude, a frequency, a pulse, a period, a pressure, and a shape of a pressure profile, when operationally coupled to the inflatable member. Because the pressure generator300is operatively coupled to the inflatable member13of the balloon catheter10via the inflation port18, the pressure generator300is directly in fluid communication with the inflatable member13via the inflation lumen located inside the catheter shaft15. In a preferred implementation, the pressure generator300is a singular device capable of modulating a pressure regime inside the inflatable member13. Alternatively, in one implementation, the balloon catheter10is operatively connected to an inflation device200and the inflation device is coupled to an additional pressure generator300, that in turn overlays a modulated pulsatile pressure profile onto e.g. a static pressure regime generated by the inflation device. In other possible implementations, the pressure generator300is directly integrated into the inflation device. Yet still, the pressure generator can be directly integrated into the inflatable member13, for example in the form of an electrohydraulic or ultrasound emitter. The pressure generator300is preferably selected from a group consisting of: an inflation device, a mechanic pressure transducer, a hydraulic pressure transducer, an electro-hydraulic pressure transducer, an ultrasound transmitter, a lithotripsy emitter, a pump and/or suitable combinations formed therefrom. Pressure generators and/or pumps can include without limitation, rotary pumps, piston pumps, gear pumps, peristaltic pumps, piezo-driven pumps, or in general, any device capable of pulsatile pressure modulation in accordance to the present disclosure.

Summarizing the above, the balloon catheter10according to the disclosure can include a pressure generator300suitable for pulsatile pressure modulation that modulates one or more of a phase, an amplitude, a frequency, a pulse, a period, a pressure, and a shape of a pressure profile when operationally coupled to the inflatable member. In the above, the pressure generator300is selected from a group consisting of: an inflation device, a mechanic pressure transducer, a hydraulic pressure transducer, an electro-hydraulic pressure transducer, an ultrasound transmitter, a lithotripsy emitter, a pump and combinations formed therefrom. Further, the pressure generator300can be provided integrated into the inflation device. Such balloon catheter10, as described in the underlying disclosure, is intended for further medical use in complex lesion treatment and for intramural drug delivery.

Controlled Percutaneous Angioplasty Procedure (C-PTA)

Different types of vascular interventional procedures and devices have been developed over the past decades to render treatment for various manifestations of arteriosclerotic disease. First generation balloon angioplasty procedures (‘plain old balloon angioplasty’, or “POBA”), typically carried out at pressures in the range of 6-8 bar over a period of a few minutes transiently achieve reperfusion of narrowed vessels by increasing luminal vessel diameter predominantly through plaque compression. Second generation angioplasty procedures, typically carried out at higher pressure ranges on the order of about 12-16 bar and over much shortened time periods of usually less than a minute, facilitate reperfusion of narrowed vessels and complex lesions predominantly by breaking up the lesion, followed by compression and/or displacement of the fractured lesion. While both first and second generation balloon angioplasty can suffer from acute elastic recoil, abrupt vessel closures and dissection, elastic recoil is less pronounced in second generation angioplasty procedures, whereas dissections tend to be more pronounced as a result of applying higher pressures. However, balloon angioplasty remains limited due to abrupt vessel closure that necessitates emergency bypass surgery in about 2 to 3% of patients, and restenosis that requires repeat revascularization in 30 to 50% of patients. Newer, next generation balloons including cutting balloons and scoring balloons have so far not been entirely successful in improving procedural efficacy in treating complex lesions, and, given an inherently higher potential for causing vessel trauma, are not likely to exceed post-procedural vessel patency rates of conventional balloon angioplasty catheters. The inventors of the present disclosure have contemplated a novel procedural approach for performing an angioplasty procedure that utilizes a combination of angioplasty balloon catheters of the present disclosure, and adjunct devices capable of performing pulsatile pressure modulation. The combination results in a controlled percutaneous transluminal angioplasty procedure (short: C-PTA), wherein optimized pulsatile pressure profiles are applied over various phases of the treatment procedure in conjunction with the angioplasty catheters of the current disclosure.

For further illustration,FIG.22provides a series of various phases of performing an angioplasty treatment in accordance with the present disclosure. InFIG.22, a diagram500denotes various pressure profiles that can be applied over the course of time of an angioplasty procedure. The Y-axis of the diagram is provided as pressure in bar units, and the X-axis is provided as procedural time in minutes. A first exemplary pressure profile106, indicated as a short dash-dotted line, depicts a pressure profile of a first generation POBA angioplasty procedure, wherein an angioplasty balloon is inflated to a pressure of about 8 bar over the course of about 0.5 to 1 minutes, and held within a lesion to be treated for about up to 3 minutes, followed by deflation and removal from the patient. A second exemplary pressure profile105, indicated as a long dash-dotted line, shows the typical progression of a second generation high pressure angioplasty procedure, wherein an angioplasty balloon is inflated to a pressure of about or exceeding 16 bar, and held within an area of treatment over a relatively short period of about 0.5 to 1 minutes, followed by deflation and removal from the patient. The angioplasty procedure according to the present disclosure separates the treatment procedure into multiple phases, and provides specific pressure profiles or regimes that are tailored to each phase. The phases are indicated on the diagram as letters A-E and demarcated on the X-Axis by dashed lines. The multi-stage angioplasty procedure comprises a series of phases, including a conditioning phase (A), a controlled lesion cracking phase (B), a mobilization phase (C), a lesion modelling phase (D) and an optional or supplemental drug delivery phase (E).

The modulated pressure profiles that are applicable in each phase of the improved angioplasty procedure, are indicated by a dotted line107, and exemplarily performed as follows:

Phase (A): The first, or conditioning phase100, consists of incrementally ramping up the pressure of the inflatable member, exemplarily in 1-3 bar increments, preferably about 2 bar increments, over an exemplarily period of between 1-2 minutes, preferably about 1.5 minutes, to a first pressure plateau, exemplarily between 2-4 bar, preferably about 4 bar. Phase A is intended to slowly unfold and atraumatically inflate the balloon to the dimensions of a target area to be treated, apposing the balloon to the lesion, ‘stretching’ the smooth muscle cells of the vessel wall, and mechanically fatiguing the lesion/plaque, thereby conditioning the lesion and initializing dilation of the lesion. The inflatable member is slowly stabilized or seated in the lesion, and inflated to a low pressure regime (about 2-4 bar) that is atraumatic with respect to potential formation of ruptures, dissections or distensions that are typically observed in high pressure angioplasty procedures. The time period for performing conditioning is selected such that the smooth muscle cells can adequately adapt to the tension exerted by the balloon, and the plaque mechanically is fatigued at the low pressure regime (about 1-2 min).

Phase (B): The second, or controlled lesion cracking phase101, consists of incrementally ramping up the pressure of the inflatable member, exemplarily in 1-3 bar increments, preferably about 2 bar increments, over an exemplarily period of between 1-2 minutes, preferably about 1.5 minutes, from the first pressure plateau, exemplarily of 2-4 bar, preferably about 4 bar to a second pressure plateau, exemplarily of 6-10 bar, preferably about 8 bar. Phase B is intended for performing controlled lesion cracking, using the inflatable member of the current disclosure, wherein the application of focalized pressure to a lesion results in a controllable fracture of the lesion at preferably multiple locations. Segmentation of the inflatable member into the at least two or more lobes induces a ‘pressure interference’ that results from the combination or overlay of the axial and radial force components at the waist portion of the inflatable member in a pressurized state. In turn, stress inflection points are controllably formed, that induce a ‘segmental inflection’ of the lesion, enabling pressure to be directionally projected into the lesion and away from the vessel wall, and thereby, facilitating an atraumatic and controlled, sequential lesion cracking. The applicable pressure regime (about 6-10 bar) is lower by design of the inflatable member of the current disclosure and consistent with the atraumatic pressure regimes of first generation POBA angioplasty catheters, which in turn are lower than second generation and high pressure balloon angioplasty catheters, and yet, suitable for compressing and displacing fibrous plaque, as well as for controllably cracking calcified plaques in complex lesions. As a result of the applied lower pressure regimes, risk of more severe dissections are reduced. The time period for performing controlled lesion cracking is selected such that the lesion/plaque continues to remain adequately mechanically fatigued at the low pressure regime (about 1-2 min).

Phase (C): The third, or mobilization phase102, consists of ramping down the pressure from the second pressure plateau, exemplarily of 6-10 bar, preferably about 8 bar, to a substantially depressurized state of the inflatable member, but without losing intimal contact to a lesion, exemplarily 0-2 bar, preferably about 0 bar, and alternatingly modulating the pressure between about 0 bar and a third pressure plateau, exemplarily of 1-3 bar, preferably about 2 bar, over an exemplary period of about 1-3 minutes, preferably 1.5 minutes. Phase C is intended to mobilize the blood flow to the treatment area and/or diseased vessel portion and to relieve built-up stress in the vessel, by temporarily relaxing and tensioning the vessel diameter. The oscillating motion of the balloon serves to ‘warm up’ respectively ‘activate’ the substantially dormant smooth muscle cells in the vessel wall at a low pressure regime, thereby facilitating increased oxygenation of the cells, and promoting subsequent revascularization of the vessel. The mobilization phase in turn prepares the vessel for the subsequent lesion modelling phase D.

Phase (D): The fourth, or lesion modelling phase103, consists of ramping up the pressure from the third pressure plateau, exemplarily of 1-3 bar, preferably about 2 bar, to a fourth pressure plateau, exemplarily 6-10 bar, preferably about 8 bar, and holding the pressure plateau, exemplarily for a period of 0.5-2 minutes, preferably 1 to 1.5 minutes, followed by ramping up the pressure to a fifth pressure plateau, exemplarily 8-14 bar, preferably about 10 to 12 bar, and holding the pressure plateau for a period, exemplarily of 0.5-2 minutes, preferably 1 to 1.5 minutes, followed by slow deflation to an end pressure of 0 bar over a period, exemplarily of 0.25 to 1 minutes, preferably of about 0.5 minutes. Phase D is intended to finalize the three-dimensional re-modelling of the vessel at a nominal diameter of the inflatable member. The inflatable member that has been seated in the lesion is inflated to its nominal diameter at a nominal pressure, using the compliance characteristics of the balloon to finalize the vessel geometry. The time period for performing modelling is selected such, that the vessel wall including smooth muscle cells can adequately adapt to the nominal diameter of the inflatable member (about greater than 1-2 min), thereby stabilizing the vessel wall including the smooth muscle cells, as well as the vessel diameter and thereby, reducing vessel recoil post modelling phase.

Phase (E): The drug delivery phase104is an optional or supplemental phase carried out prior to, during, or after the series of phases A-D have been completed, using for example an inflatable member as described inFIG.7of the present disclosure. Phase E is intended to further improve the clinical long-term effectiveness of the angioplasty procedure through the administration of therapeutic agents, that can help accelerate healing, prevent inflammation, suppress restenosis of the diseased vessel portion, among other possible indications.

The above described multi-phase angioplasty procedure favorably combines the advantages of the first and second generation angioplasty procedures without having their specific drawbacks, and thereby, enables a high-quality, controlled percutaneous transluminal angioplasty (C-PTA).

The specific pressure regimes, as well as the specific time periods for ramping up, maintaining pressure and ramping down in the aforementioned angioplasty procedure are of exemplary nature and not intended to be limiting. The specific pressure regimes and time periods may vary according to additional procedural factors and clinical indication, including vessel anatomy, length and diameter of device and lesion, among others.

Summarizing the described method for treating a vascular pathology with a balloon catheter10according to the underlying disclosure, the method comprises a series of phases including:Performing a first, or conditioning phase100;Performing a second, or controlled lesion cracking phase101;Performing a third, or mobilization phase102, andPerforming a fourth, or lesion modelling phase103.

Alternatively or supplementally, in the above method, the series of phases can further include:Performing one or more drug delivery phase104.

With respect to the foregoing,the first, or conditioning phase100consists of ramping up the pressure of the inflatable member in 2 bar increments over a period of 1.5 minutes to a first pressure plateau of about 4 bar;the second, or controlled lesion cracking phase101consists of ramping up the pressure in 2 bar increments over a period of 1.5 minutes from the first pressure plateau of about 4 bar to a second pressure plateau of about 8 bar;the third, or mobilization phase102consists of ramping down the pressure from the second pressure plateau of about 8 bar to about 0 bar, and alternatingly modulating the pressure between 0 bar and a third pressure plateau of about 2 bar over a period of about 1.5 minutes, andthe fourth, or lesion modelling phase103consists of ramping up the pressure from the third pressure plateau of about 2 bar to a fourth pressure plateau of about 8 bar, and holding the pressure plateau for a period of 1 to 1.5 minutes, followed by ramping up the pressure to a fifth pressure plateau of about 10 to 12 bar and holding the pressure plateau for a period of 1 to 1.5 minutes, followed by slow deflation to an end pressure of 0 bar over a period of about 0.5 minutes.

Regarding the optional or supplemental phase of the series of phases, the drug delivery phase104consists of:partially inflating the at least two lobes of the inflatable member to occlude a blood flow to an area to be treated;administering therapeutic agents from the perfusion port across the drug perfusion lumen51and drug release opening50to a waist region77located in the area to be treated (65,66);maintaining a therapeutic treatment time;
withdrawing residual therapeutic agents into the drug perfusion lumen51, anddeflating the at least two lobes32,34of the inflatable member13to restore blood flow to the target treatment area.

In any of the above, the series of phases can include pressure regimes or profiles107applied with static and pulsatile pressure modulation. Further, the pulsatile pressure modulation can be performed in one or more phases.

The foregoing description, for purposes of explanation, refers to specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that the specific details are not required in order to practice the invention. The foregoing descriptions of specific implementations of the present invention are presented for purpose of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Certainly many modifications and variations are possible in view of the above teachings. The embodiments are shown and described in order to best explain the principles of the invention and practical applications, to thereby enable others skilled in the art to best utilize the invention and various implementations with various modifications as suitable for the particular uses contemplated. It is intended that the scope of the invention be defined by the following claims and their equivalent.