HK40074744A - Apparatus and methods for restoring tissue - Google Patents

Description

Device and method for repairing tissue

Cross Reference to Related Applications

This application claims priority from U.S. patent application No. 16/527,969 filed on 31/7/2019, which is hereby incorporated by reference in its entirety.

Technical Field

The present disclosure relates generally to devices and methods for repairing tissue function. Embodiments disclosed herein relate more particularly, but not by way of limitation, to catheters and catheter systems for creating natural vascular stents and repairing tissue function.

Background

Balloon catheters are used in many surgical applications, including blocking the distal or proximal flow of blood to a treatment site. Inflation of the balloon must be controlled in order to avoid over-inflation or breakage of the balloon, which can result in the vessel being ruptured or otherwise damaged. Percutaneous Transluminal Angioplasty (PTA), in which a balloon is used to open an occluded artery, has been widely used to treat atherosclerotic lesions. However, this technique is limited by the troublesome problems of re-obstruction and restenosis. Restenosis is caused by Smooth Muscle Cell (SMC) hyperproliferation, and the rate of restenosis is above 20%. Therefore, about one fifth of patients receiving PTA treatment must receive treatment again within several months.

In addition, stenting is a popular treatment in which a stenotic arteriosclerotic segment of an artery is mechanically dilated with the aid of a balloon catheter, and a metal stent is then placed within the lumen of the vessel to restore blood flow. Constriction or blockage of the artery is problematic and may itself be or lead to serious health complications. It has been found that in 20% to 30% of patients, placement of a metal stent can result in the need for post-operative treatment. One of the reasons for such high frequencies of post-operative treatment is the development of intimal hyperplasia within the vessel lumen, resulting in a narrowing of the lumen despite the placement of the stent. In order to reduce in-stent restenosis, attempts have been made to design a type of stent having a surface carrying a restenosis-inhibiting drug such that when the stent is placed in an artery, the drug is eluted in a controlled manner within the lumen of the vessel. These attempts have made commercialization of drug-eluting stents (hereinafter referred to as DES) using sirolimus (immunosuppressant) and paclitaxel (cytotoxic antitumor drug). However, since these drugs have the effect of inhibiting the proliferation of vascular cells by acting on the cell cycle of vascular cells (endothelial cells and smooth muscle cells), these drugs can inhibit not only the intimal hyperplasia of blood vessels caused by the excessive proliferation of smooth muscle cells but also the proliferation of endothelial cells upon causing the drugs to exfoliate during the stent placement. This may result in a reduction in adverse effects of repair or treatment of the intima of the blood vessel. In view of the fact that thrombus formation tends to occur more easily at sites of the intima of blood vessels where endothelial cells cover less, it is necessary to administer an antithrombotic agent for a long time (i.e., about half a year), and in spite of the administration of such an antithrombotic agent, there is a risk of late thrombus formation and restenosis occurring after drug withdrawal.

The technical problem addressed by the present disclosure is therefore to overcome these prior art difficulties by creating a device for controlled delivery of therapeutic agents to surrounding tissue, expanding blood vessels to a final shape, functionalizing the therapeutic agents within the tissue and forming a cast shape, allowing blood flow and repairing tissue function. A solution to this technical problem is provided by the embodiments described herein, characterized by the claims.

Disclosure of Invention

Embodiments of the present disclosure include catheters, catheter systems, and methods of forming tissue scaffolds using the catheter systems. Advantageously, the exemplary embodiments allow for controlled, uniform delivery of therapeutic agents to surrounding tissue, casting the tissue into a final shape, functionalizing the therapeutic agents in the tissue forming the cast shape, and stenting the vessel. The tissue may be a vessel wall of a vessel within the cardiovascular system.

According to an embodiment of the present disclosure, an apparatus is provided. The apparatus may include: a catheter shaft extending from a proximal end to a distal tip; and a first distal balloon positioned on the translucent distal section of the catheter shaft adjacent the distal tip and positioned within and concentric with the second distal balloon. The first distal balloon may be in fluid communication with a drug source via a first lumen. The first distal balloon may comprise: a translucent material, a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon, and a plurality of circumferential channels recessed from an outermost radial surface of the first distal balloon. The apparatus may include: a second distal balloon in fluid communication with a second lumen separate from the first lumen; and a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section.

In some embodiments, the second distal balloon includes a plurality of slit openings radially aligned with an outermost radial surface of the first distal balloon that selectively communicate the drug from the first distal balloon to a treatment area of the subject. These slit openings are positioned away from the longitudinal and circumferential channels of the first distal balloon. The slit opening of the second distal balloon may remain in contact with the outermost radial surface of the first distal balloon, thereby sealing the slit opening during inflation and deflation of the first distal balloon. During inflation of the second distal balloon, fluid fills between the inner surface of the second distal balloon and the outer surface of the first distal balloon, thereby gradually filling the longitudinal and circumferential channels. The pressure of the fluid between the inner surface of the second distal balloon and the outer surface of the first distal balloon increases and inflates the second distal balloon, the increased pressure forcing the edges of the slit opening apart, thereby reducing the pressure. Inflation of the second distal balloon moves the slit opening away from the outermost radial surface of the first distal balloon, allowing the slit opening to open and fluid to flow to the treatment area.

In some embodiments, the translucent material of the distal section, the first distal balloon, and the second distal balloon is transparent. The first and second optical fibers may provide light activation through the distal section, the first distal balloon, and the second distal balloon. The longitudinal and circumferential channels are non-deformable and provide uniform drug delivery through the second distal balloon. The second distal balloon may include a material conforming to the morphology of the vessel wall.

Embodiments of the present disclosure also provide a method of tissue repair in a blood vessel of a subject. The method may include positioning a catheter into a blood vessel. The catheter may include: a catheter shaft extending from a proximal end to a distal tip; and a first distal balloon positioned on the translucent distal section of the catheter shaft adjacent the distal tip and positioned within and concentric with the second distal balloon. The first distal balloon may be in fluid communication with a drug source via a first lumen. The first distal balloon may comprise: a translucent material, a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon, and a plurality of circumferential channels recessed from an outermost radial surface of the first distal balloon. The apparatus may include: a second distal balloon in fluid communication with a second lumen separate from the first lumen; and a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section. The method can comprise the following steps: supplying a drug from a drug source to the first distal balloon; delivering the drug to the treatment area through the slit opening; and activating the first and second optical fibers to provide light transmission through the distal section, the first distal balloon, and the second distal balloon to activate the drug in the treatment area.

The method may further comprise: gradually filling a drug into the volumes of the longitudinal and circumferential channels between the inner surface of the second distal balloon and the outer surface of the first distal balloon; and inflating the second distal balloon, thereby moving the slit opening away from an outermost radial surface of the first distal balloon. The method may further include deflating the second distal balloon while fluid is being delivered through the slit opening. Deflating the second distal balloon can move the second distal balloon into contact with the outermost radial surface of the first distal balloon and close the slit opening, causing drug delivery to stop.

Embodiments of the present disclosure also provide an apparatus, comprising: a catheter shaft extending from a proximal end to a distal tip; and a first distal balloon positioned on the translucent distal section of the catheter shaft adjacent the distal tip and positioned within and concentric with the second distal balloon. The first distal balloon may be in fluid communication with a drug source via a first lumen. The first distal balloon may comprise: a translucent material, a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon, and a plurality of circumferential channels recessed from an outermost radial surface of the first distal balloon. The apparatus may include: a second distal balloon in fluid communication with a second lumen separate from the first lumen; and a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section. The drug source is configured to provide at least one drug to the first distal balloon via the first lumen, and during inflation of the second distal balloon, a fluid fills between an inner surface of the second distal balloon and an outer surface of the first distal balloon, gradually filling the longitudinal and circumferential channels.

Additional features and advantages of the embodiments disclosed herein will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the embodiments disclosed herein. The features and advantages of the embodiments disclosed herein will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the embodiments disclosed herein, as claimed.

The accompanying drawings form a part of the specification. The accompanying drawings illustrate several embodiments of the present disclosure and, together with the description, serve to explain the principles of the embodiments disclosed herein set forth in the appended claims.

Drawings

Fig. 1 is a side view of an exemplary device including a catheter according to an embodiment of the present disclosure.

Fig. 2 is a side view of the distal portion of the catheter of fig. 1.

Fig. 3 is a perspective view of an exemplary first balloon of the exemplary catheter of fig. 1.

Fig. 4 is a perspective view of an exemplary second balloon of the exemplary catheter of fig. 1.

Fig. 5A is a cross-sectional view taken along line 5A-5A of fig. 2.

Fig. 5B and 5C are cross-sectional views taken along line 5B-5B of fig. 2A, with portions of the outer structure removed.

Fig. 6 is a detail perspective view of the first balloon of fig. 3.

FIG. 7 is a perspective cross-sectional view taken along line 6-6 of FIG. 4 with portions of the internal structure removed.

Fig. 8A-8F show a series of internal perspective views illustrating a filling sequence according to an embodiment of the present invention.

Detailed Description

Reference will now be made in detail to embodiments and aspects of the present disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

Fig. 1 shows an apparatus 100 according to an embodiment of the present disclosure. The device 100 has a catheter shaft 104 extending from a proximal end 106 of the device 100 to a distal tip 110. The device 100 may be configured for longitudinal movement and positioning within a vessel (e.g., blood vessel) of a subject. In some embodiments, the device 100 may be configured to treat a region of a blood vessel. In some embodiments, the device 100 may occlude a blood vessel, while in other embodiments, the device may not occlude a blood vessel. For example, the device 100 may be configured for delivering a drug to a region of a blood vessel occupied by the device 100, which may be formed and cast in shape in the blood vessel, as will be described in more detail below.

The device 100 may include a proximal end connector 114 positioned at a proximal end of the device 100, and the catheter shaft 104 may extend distally therefrom. The catheter shaft 104 may define a plurality of lumens accessible via a plurality of ports of the proximal end connection 114. The plurality of ports 115 may be configured to engage with an external source that is desired to communicate with the plurality of lumens. These ports may be engaged with an external source by a variety of connection mechanisms, including but not limited to a syringe, over-molding, quick-disconnect coupling, latching connection, barbed connection, keyed connection, threaded connection, or any other suitable mechanism for connecting one of the ports to an external source. Non-limiting examples of external sources may include an inflation source (e.g., saline solution), a gas source, a therapeutic source (e.g., a prescription drug, a drug, or any desired therapeutic agent discussed further below), a light source, and the like. In some embodiments, the device 100 may be used with a guidewire (not shown) via a guidewire lumen 164 (see fig. 5A) to assist in guiding the catheter shaft 104 to a target region of a blood vessel.

Fig. 1,2, and 3 show that the device 100 may include a first distal balloon 120 positioned on a distal section 130 of the catheter shaft 104 adjacent the distal tip 110, within and concentric with a second distal balloon 122. In some embodiments, the first distal balloon 120 may be proximally offset from the distal tip 110 by a distance of 0mm to 1mm, 0mm to 2mm, 0mm to 3mm, 0mm to 10mm, or 0mm to 50 mm. When inflated, the first distal balloon 120 may take any shape suitable for supporting a vessel wall or other hollow body structure of a subject.

The second distal balloon 122 may have one continuous surface that is sealed at each end to form an enclosed volume around the catheter shaft 104 and is in fluid communication with the catheter shaft 104 with a port through a different and separate lumen than the first distal balloon 120. The second distal balloon 122 may be substantially translucent. In some embodiments, the second distal balloon 122 is expandable to a diameter of 2 millimeters to 10 millimeters (mm). In other embodiments, the second distal balloon 122 may be inflated to a diameter of up to 1cm to 8 cm. The second distal balloon 122 may have a length of about 0.5cm to 1cm, 1cm to 2cm, 1cm to 3cm, or 1cm to 5cm, or 1cm to 10cm, or 1cm to 15cm, or 1cm to 20cm, or 1cm to 25cm, and may assume any shape suitable for supporting a vessel wall of a subject when the non-compliant or semi-compliant balloon is inflated. For example, the second distal balloon 122 may expand into a cylindrical shape around the distal section 130 of the catheter shaft 104. The cylindrical shape may taper inwardly at the proximal and distal ends of the second distal balloon 122, providing tapered proximal and distal ends of the second distal balloon 122 that taper into contact and become flush with the catheter shaft 104.

Non-limiting examples of shapes that the inflated second distal balloon 122 may form include cylindrical, football, spherical, elliptical, or may be selectively deformed in a symmetric or asymmetric shape in order to limit potential differences in treated and untreated vessel shapes, thereby reducing edge effects between two surfaces of different stiffness commonly found in metal stents. The force applied by the second distal balloon 122 to the interior of the blood vessel may be strong enough to support the vessel wall in the event that the device 100 is held in a fixed position within the blood vessel or other hollow body structure. However, the force is not so great as to damage the interior surface of the vessel or other hollow body structure.

Device 100 may include a plurality of links 115 positioned proximal to proximal end link 114. For example, the first distal balloon 120 may terminate at a proximal end at a connection configured to receive a drug source. In some embodiments, the connector may be a luer configuration. The second distal balloon 122 may terminate at a proximal end in a separate and distinct connector capable of receiving fluid for inflation, which in some embodiments may be a luer configuration. The central lumen (discussed in more detail below) may terminate at the proximal end in a connection capable of receiving a fluid source for cleaning the lumen from the proximal terminal end to outside the distal tip, and in some embodiments, the connection may comprise a luer configuration. The central lumen may also house a guidewire for tracking the catheter device to a desired anatomical location. As discussed in more detail below, the device 100 may also include an optical fiber that may terminate at a proximal end in an adapter capable of connecting to a light source. Each fiber may terminate in a separate and distinct adapter, or each fiber may share one adapter connected to the light source.

The material of the device 100 may be biocompatible. The catheter shaft 104 may comprise a material that is compressible and capable of maintaining the integrity of the lumen. The distal section 130 of the catheter shaft 104 is substantially translucent to allow light transmission from the optical fiber. The catheter shaft 104 material is sufficiently rigid to track with a guidewireAnd is flexible enough to prevent injury. The catheter shaft 104 may be made of materials including, but not limited to: polymers, natural or synthetic rubbers, metals and plastics or combinations thereof, nylons, polyether block amides (PEBA), nylon/PEBA blends, thermoplastic copolyesters (TPC), a non-limiting example of which may be(available from Dupont de Nemours, inc. of wilmington, delaware) and polyethylene. The shaft material may be selected to maximize column strength based on the longitudinal length of the shaft. In addition, the shaft material may be braided to provide sufficient column strength. The shaft material may also be selected to allow the device to move smoothly along the guidewire. The catheter shaft 104 may also be provided with lubricious coatings as well as antimicrobial and anticoagulant coatings. The shaft material should be selected so as not to interfere with the efficacy of the agent to be delivered or collected. This interference may be manifested as absorption of the agent, adherence to the agent, or any way of altering the form of the agent. The catheter shaft 104 of the present disclosure may be between about 2 french units to 16 french units (abbreviated "Fr." where one french unit equals 1/3 millimeters, or about 0.013 inches). The catheter shaft for the coronary artery may have a diameter of between about 3Fr. and 5Fr., and more particularly may be 3 Fr.. The catheter shaft for the peripheral vessel may have a diameter of between about 5Fr. and 8Fr., and more particularly may be 5 Fr.. The catheter shaft for the aorta may have a diameter of between about 8Fr. and 16Fr., and more particularly may be 12 Fr..

The first distal balloon 120 and the second distal balloon 122 may be substantially translucent, allowing light from the optical fiber to be substantially transmitted beyond the inflated diameter of the second distal balloon 122. The second distal balloon 122 can be compliant such that the material substantially conforms to the morphology of the blood vessel. The first distal balloon 120 material may be more rigid and non-compliant, able to withstand higher internal pressures with minimal outward expansion, thereby opening the vessel in a more pressure resistant manner. The compliance of the first distal balloon and the second distal balloon may be the same or different. For example, first distal balloon 120 may be non-compliant, capable of withstanding higher internal pressures with minimal outward expansion, for dilating and casting a vessel into an optimal shape. The second balloon 122 material may be elastic, capable of covering the first distal balloon 120 as a sheath or covering, expanding and contracting as the first distal balloon 120 expands, and substantially elastically conforming to the vessel morphology for optimal drug delivery. The second distal balloon 122 may comprise a material that conforms to the morphology of the vessel wall to provide optimal drug delivery in a non-distensible and non-traumatic manner. The device 100 does not cause any further trauma to the vessel (e.g., trauma caused by atherectomy or percutaneous transluminal angioplasty "PTA" or vessel preparation methods) to promote optimal healing.

To optimize performance, the balloon may be thick or thin. The first distal balloon 120 may be thicker (0.002 inches) to better form the fluid channel and support the vessel wall for shaping. The second distal balloon may be thicker (0.002 inches) to better form the opening and closing function of the perforations 198 described in more detail below.

Fig. 3 is a perspective view of the first distal balloon 120 with the surrounding second distal balloon 122 removed. In some embodiments, first distal balloon 120 may not be a percutaneous transluminal angioplasty balloon or a high pressure device, rather, first distal balloon 120 may be non-distensible and used to form a vessel shape or to dilate a vessel. First distal balloon 120 includes a plurality of longitudinal fluid channels 124 and a plurality of circumferential fluid channels 126. Longitudinal fluid channels 124 extend along the length of first distal balloon 120, each longitudinal fluid channel 124 is spaced apart from other longitudinal fluid channels 124, and each longitudinal fluid channel 124 intersects a plurality of circumferential fluid channels 126 along the length of first distal balloon 120. The longitudinal fluid channels 124 and the circumferential fluid channels 126 may intersect at an angle of 10 ° to 170 °. Circumferential fluid channels 126 extend around the circumference of first distal balloon 120, each circumferential fluid channel 126 being spaced apart from the other circumferential fluid channels 126. Longitudinal fluid channel 124 and circumferential fluid channel 126 each have a depth, wherein the depth of the fluid channels is measured relative to an outer surface 127 of first distal balloon 120. Thus, the longitudinal fluid channels 124 and the circumferential fluid channels 126 are recessed from the outer surface 127 of the first distal balloon 120. The depth of the longitudinal fluid channels 124 and the depth of the circumferential fluid channels 126 may be the same or different. The longitudinal fluid channels 124 and the circumferential fluid channels 126 may be non-deformable. In some embodiments, the fluid channels 124, 126 facilitate folding of the first distal balloon 120.

Fig. 4 shows a second distal balloon 122, which may comprise an elastic and substantially translucent material, may be capable of maintaining contact with the outermost radial surface of the first distal balloon 120, and may serve as a covering or skin for the first distal balloon 120 during inflation and deflation of the first distal balloon 120. The second distal balloon 122 may include a plurality of perforations 198 that penetrate the balloon wall. The perforations 198 may be slit openings. As described in more detail below, the slit openings 198 may be in fluid communication from the inner surface of the second distal balloon 122 to the outer surface of the second distal balloon 122. Perforations 198 may be formed in an expanded or distended material state, such that in a deflated or contracted state, the perforations remain naturally closed.

Fig. 5A is a cross-sectional view taken along line 5A-5A of fig. 2 showing a plurality of lumens within assembly 100, in accordance with an embodiment of the present disclosure. The catheter shaft 104 may have an outer diameter and an outer surface 130. The catheter shaft 104 may have an internal configuration of five distinct and separate lumens extending from the proximal end 106 to the distal tip 110.

The first distal balloon 120 may be in fluid communication with a first distal balloon inflation lumen 150. The second distal balloon 122 may be in fluid communication with a second distal balloon inflation lumen 154 that is separate and distinct from the first distal balloon inflation lumen 150. The first distal balloon 120 may be in fluid communication with an inflation source via a first distal balloon inflation lumen 150 that is separate from a second distal balloon inflation lumen 154. The first distal balloon inflation lumen 150 may extend through the catheter shaft 104 and have an input at one of the plurality of ports 115 of the proximal end connector 114. Fluid communication between the first distal balloon 120 and the inflation source via the first distal balloon inflation lumen 150 may allow the first distal balloon 120 and the second distal balloon 122 to be separately and independently selectively filled. Similarly, the second distal balloon 122 may be in fluid communication with an inflation source via a second distal balloon inflation lumen 154 that is separate from the first distal balloon inflation lumen 150. Fluid communication between the second distal balloon 122 and an inflation source via the second distal balloon inflation lumen 154 may separate and independently selectively inflate and deflate the second distal balloon 122 from the first distal balloon 120.

The first and second fiber lumens 158, 160 may be positioned in the catheter shaft 104 to receive optical fibers, and the first and second fiber lumens 158, 160 may extend from the proximal end 106 into the distal section 130 and may be positioned substantially symmetrically, longitudinally opposite and parallel to each other within the catheter shaft 104. In another exemplary embodiment, the catheter shaft 104 may include a single fiber lumen. In other embodiments, the catheter shaft 104 may include a plurality of fiber optic lumens.

The guidewire lumen 164 may be concentric with the catheter shaft outer diameter and may be disposed in the catheter shaft 104 from the proximal end 106 to the distal tip 110. The guidewire lumen 164 may house a guidewire to aid in placement of the device 100 to a desired anatomical location in communication with the proximal end and the distal tip. The guidewire may be separate and distinct from the device 100 and extend proximally beyond the proximal end of the catheter shaft and distally beyond the distal tip. The guidewire lumen 164 is positioned concentric to the catheter outer diameter, the catheter shaft being oriented concentrically with the guidewire, allowing the catheter shaft 104 to follow the guidewire rather than being biased to one side of the catheter shaft 104 or sloshing between the two sides. The guidewire may be held in the guidewire lumen 104, maintained in an anatomical position during activation of the optical fiber.

Fig. 5B and 5C show cross-sectional views taken along line 5B-5B of fig. 2. The device 100 may also include a first optical fiber 140 and a second optical fiber 142 positioned in the catheter shaft 104 and extending through the distal section 130. The optical fibers 140, 142 may transmit light through the distal section 130, the second distal balloon 122, the first distal balloon 120. The optical fiber 140 may be connected to the proximal end connector 114 and may have a proximal end connected to a fiber activation source via at least one port of the plurality of ports 115. In some embodiments, the optical fibers 140, 142 can be configured to transmit 375 nanometers (nm) to 475nm wavelength light, and more specifically 450nm wavelength light, which is transmitted through the distal section 130 and the first distal balloon 120. The optical fibers 140, 142 may emit light outside the Ultraviolet (UV) range (10nm to 400 nm). In some embodiments, the first optical fiber 140 may be positioned in the first fiber lumen 158 and the second optical fiber 142 may be positioned in the second fiber lumen 160.

In some embodiments, light from the optical fibers 140, 142 may not penetrate the guidewire 144, forming a shadow 145 opposite the light and beyond the guidewire 144. Accordingly, the optical fibers 140, 142 may each generate a respective light-transmitting region 146. The fiber lumens 158, 160 are oriented substantially opposite one another so as to minimize the shadow 145 formed by the light-impermeable guidewire 144, allowing light to be transmitted from the first optical fiber 140 or the second optical fiber 142 through the circumference of the catheter shaft 104. In another embodiment, the catheter shaft 140 may include a single optical fiber, and the guidewire may be removed for light penetration to external tissue.

In some embodiments, the optical fibers 140, 142 may be made of a plastic core and cladding. The refractive index of the core is high. The refractive index of the cladding is low. A non-limiting example of the core material may be Polymethylmethacrylate (PMMA). A non-limiting example of a cladding layer may be a silicone material. The light source may control the wavelength and power provided by the optical fibers 140, 142. The morphology of the break in the fiber cladding ensures an even distribution of power to the vessel wall. The longer length has a different morphology than the shorter length. The distal length of the cladding break matches the length of the balloon.

As shown in fig. 3 and 6, the longitudinal fluid channels 124 and the circumferential fluid channels 126 may form an interconnected configuration. Interconnected longitudinal fluid channels 124 and circumferential fluid channels 126 having this configuration create a volume in which fluid may fill the channels. The longitudinal fluid passages 124 and the circumferential fluid passages 126 form an outermost radial surface (e.g., outer surface 127) and an innermost radial surface (e.g., inner surface 128). The outermost radial surface 127 may contact the vessel wall and may shape or cast the vessel, distracting the vessel without overstretching or greatly expanding the vessel wall.

As shown in fig. 6, the innermost radial surface 128 allows fluid to flow longitudinally and circumferentially along directional arrows, supplying fluid throughout the innermost surface 128 of the first distal balloon 120 for subsequent uniform delivery through the second distal balloon 122, as described below. Longitudinal channels 124 promote longitudinal fluid flow along the flow direction arrows, and circumferential channels 126 promote circumferential fluid flow along the flow direction arrows. The number of fluid passages (e.g., longitudinal passage 124 and circumferential passage 126), outermost radial surface 127, and innermost radial surface 128 may be varied to optimize the delivery function, and maintain shape and function throughout the expansion pressure range for a continuous fluid supply. In some embodiments, the longitudinal fluid channel 124 may allow for preferential material defects to fold the balloon.

Fig. 7 shows that second distal balloon 122 may have a thickness 194 forming an outer surface 195 and an inner surface 196. The inner surface 196 forms a confined and isolated volume 170 that is in fluid communication with the proximal end 106 of the catheter shaft 104 and the plurality of slit openings 198. The second distal balloon 122 may comprise an elastic and substantially translucent material capable of maintaining contact with the outermost radial surface 127 of the first distal balloon 120, acting as a covering or sheath during inflation and deflation of the second distal balloon 122. The second distal balloon 122 may comprise a resilient and substantially non-translucent porous membrane (ePTFE) material capable of allowing substantial light transmission and capable of maintaining contact with the outermost radial surface 127 of the first distal balloon 120, acting as a covering or sheath during expansion and contraction of the second distal balloon 122. The second distal balloon 122 may include a plurality of slit openings 198, which may be perforations through the thickness 194 of the wall of the second distal balloon 122, fluidly communicating from the inner surface 196 of the balloon 122 to the outer surface 195 of the balloon 122.

The slit openings 198 may be arranged in a circumferential and/or longitudinal pattern. Slit opening 198 is located in a region 197 radially aligned with outermost radial surface 127 of first distal balloon 120 and catheter shaft 104, and is substantially absent in a region 199 aligned with innermost radial surface 128 where longitudinal fluid channels 124 and circumferential fluid channels 126 are located. "substantially absent" may refer to a slit opening positioned away from a first distal balloon region of the innermost radial surface 128 where the longitudinal fluid passage 124 and the circumferential fluid passage 126 are located. This configuration allows the slit opening 198 of the second distal balloon 122 to remain in contact with the outermost radial surface 127 of the first distal balloon 120, thereby sealing the slit opening 198 during inflation and deflation of the first distal balloon 120. The slit opening 198 may only open and allow fluid flow when the second distal balloon 122 is subsequently inflated. Inflation of the second distal balloon 122 lifts the slit opening 198 away from the outermost radial surface 127 of the first distal balloon 120. Inflation of the second distal balloon 122 moves the slit openings 198 away from the outermost radial surface 127, which allows the slit openings 198 to function as microvalves and selectively deliver fluid to the vessel wall. The second distal balloon 122 may include at least one slit opening 198 having a maximum length that is substantially the same as the length of the outermost surface 195 (i.e., eight outermost surfaces 195, eight slit openings 198 having a length that is the same as the length of the outermost surface 195). The number and length of the slit openings 198 may be varied to suit the desired function; however, for proper operation, this configuration must be followed to ensure that there are no slit openings 198 near the longitudinal fluid passage 124 and the circumferential fluid passage 126 of the first distal balloon 120.

Fig. 8A-8F illustrate an expansion sequence according to embodiments of the present disclosure. Although the second distal balloon 122 is not specifically shown in fig. 8A-8F, the second distal balloon 122 is inflated due to the fluid pressure generated in the fluid configuration as shown in fig. 8E and 8F.

The first distal balloon 120 is inflated to form a substantially constant fluid passage structure covered by a second distal balloon 122, which may be resilient. As shown in fig. 8A-8C, the fluid 200 first fills the longitudinal fluid channels 124 and the circumferential fluid channels 126, the fluid 200 filling between the innermost surface 128 and the outermost surface 127 of the first distal balloon 120 and the inner surface 196 of the second distal balloon 122, away from the slit opening 198 aligned with and in contact with the outermost surface 127 of the first distal balloon 120. The fluid pressure gradually increases in the volume between the innermost surface 128 and the outermost surface 127 of the first distal balloon 120 and the inner surface 196 of the second distal balloon 122, which causes the resilient second distal balloon 122 to begin to move away from the outermost surface 127 of the first distal balloon 120, thereby allowing the fluid 200 to begin to flow onto the outermost surface 127, as shown in fig. 8D. As the pressure continues to increase, the second distal balloon 122 continues to inflate, allowing the fluid 200 to flow evenly around the outer surface 127 of the first distal balloon 120 and the fluid channel (fig. 8E) until the second distal balloon 122 is fully inflated and the fluid 200 begins to flow through the slit opening 198 (after fig. 8F is achieved).

The fluid 200 may be a source of a drug and provide therapeutic purposes when functionalized with a light source of appropriate wavelength. Along the path of least resistance, the inflation fluid 200 of the second distal balloon 122 will fill the circumferential channels 126 and the longitudinal fluid channels 124 of the first distal balloon 120. Without the slit opening 198 in the second distal balloon 122, the innermost radial surface 128 or fluid channel 124 or fluid channel 126 of the first distal balloon 120 would be substantially filled with the fluid 200 in the region of the innermost radial surface 128 or fluid channel (e.g., 124, 126) of the first distal balloon 120. The slit opening 198 of the second distal balloon 122 remains in contact with, seals, and closes the outermost radial surface 127 of the first distal balloon 120. Once the first distal balloon fluid channels 124, 126 are filled, further inflation of the second distal balloon 122 will cause the material to expand, thereby lifting the slit opening 198 away from the first distal balloon outermost surface 127, opening and unsealing the slit opening 198, and allowing the fluid 200 to flow through the slit opening 198. Once inflation ceases, the fluid 200 will flow out of the unsealed slit opening 198 until only the fluid passages 124, 126 of the first distal balloon are filled, allowing the inner surface 196 of the second distal balloon 122 to adhere to the outermost radial surface 127 of the first distal balloon 120, again closing and sealing the slit opening 198. In this manner, inflating and deflating the second distal balloon 122 can selectively control the delivery of the drug source, acting as a series of microvalves in "open" and "closed" states. Similarly, second distal balloon 122 may be a porous membrane material having small pores at low pressure and larger pores at high pressure. The first distal balloon 120 operates and performs as described. Second distal balloon 122 operates and performs as described, filling fluid channel 124 and fluid channel 126 prior to contacting inner surface 196; in addition, the pores of the second distal balloon 122 remain closed until the pressure increases sufficiently to open the pores and allow the drug to flow from the outer surface of the first distal balloon 120 to the outer surface of the second distal balloon 122, acting as a series of microvalves in "open" and "closed" states.

The target area for delivery of the drug source may be a blood vessel of the cardiovascular system. The target area may first be prepared by Percutaneous Transluminal Angioplasty (PTA) or atherectomy to divert or remove damaged vascular cell debris. The catheter device 100 is not intended to replace PTA; the functional pressure of the first distal balloon 120 is only sufficient to dilate the vessel during drug functionalization. The first distal balloon 120 may be inflated to form a fluid channel (e.g., 124, 126); the outermost radial surface 127 is in contact with the inner surface 196 of the second distal balloon 122. The second distal balloon 122 is inflated with the drug source, first filling the fluid channels 124, 126 of the first distal balloon 120, and then lifting the slit openings 198 away from the first distal balloon outermost radial surface 127 to uniformly deliver the drug source to the vessel wall.

If the slit openings 198 are positioned at or near smaller vessels, side branches, only the drug from those slit openings 198 will be lost to those smaller vessels. However, all remaining slit openings 198 will deliver the drug to the vessel wall adjacent thereto, so that the drug is delivered uniformly to the vessel wall with minimal loss in other areas. In some embodiments, the light source may be activated during or after drug delivery when the first distal balloon 120 is inflated, expanding the vessel wall, and shaping the vessel diameter.

The edges of the slit opening 198 may be held together and closed, the first and second distal balloons 120, 122 being filled with the drug source, allowing the first and second distal balloons 120, 122 to be nearly filled and inflated without losing the drug source. As the volume of the second distal balloon 122 fills and expands, the pressure will increase, forcing the edges of the slit opening 198 open and allowing fluid to flow out through the slit opening 198, thereby reducing the balloon pressure. Similarly, when the volume and corresponding pressure of the second distal balloon 122 decreases as fluid flows out through the slit opening 198, the edges of the slit opening 198 may close together and may prevent fluid from flowing through the slit opening 198 when they come into contact with the outer surface 127 of the first distal balloon 120. Inflating and deflating the first distal balloon 120 and the second distal balloon 122 in this manner may control the delivery of the drug source as the slit opening 198 is opened and closed.

In some embodiments, the device 100 is capable of delivering two drugs simultaneously. For example, the exterior of the second distal balloon 122 may be coated with a first drug and a second drug may be delivered through the slit opening 198. Thus, the first drug and the second drug may be different drugs. In some embodiments, the first drug and the second drug may be the same drug. In a non-limiting example, the inner or outer surface of the second distal balloon 122 may be coated with paclitaxel and an aqueous drug or saline is injected through the slits into the vessel wall.

When in this position to support the vessel, the light source may be supplied to the optical fibers 140, 142 in the catheter shaft 104 as previously described to transmit through the catheter shaft 104, through the first and second distal balloons 120, 122, and into the vessel wall 182.

There are several combinations for locally delivering drug sources. For example, a solid drug may be coated on the outer surface of the second distal balloon 122 and an aqueous drug may be delivered through the slit opening 198 of the second distal balloon 122. The drugs may be the same (one solid and one aqueous), each penetrating the vessel wall in a different manner. These drugs may be complementary but distinct substances (e.g., one drug may cross-link collagen for repairing vascular properties, while a complementary drug may be antiproliferative for reducing surgery-related inflammation). Aqueous or solid drugs can help excipients to act or activate their counterparts through a controlled reaction. These drugs may be different and non-complementary, acting on the vessel wall by widely different methods of action. The drugs may be delivered sequentially, one after the other, or with a timed delay, or multiple deliveries at the same location, or multiple deliveries at subsequent locations, by the same device (e.g., 100), to achieve the most effective treatment. These drugs may be functionalized with a light source at the same time as delivery (i.e., the light source remains on during drug delivery through the slit opening 198). The drug may be effective when the drug is proximate to the tissue component and functionalized by the light source.

In some embodiments, the drug is functionalized to crosslink with tissue proteins, although the drug is not effective or activated. Tissue proteins, drugs and light can produce therapeutic effects. The functionalization of the drug may not be time dependent, but transient, depending only on the wavelength. Optical power can compensate for losses through the optical fiber, the two balloons, and the tissue wall, and can be balanced to avoid heat build-up during treatment.

In some embodiments, the device 100 may provide therapy with multiple aqueous drugs having different methods of action. When a blood vessel is dilated, one drug can be delivered first and functionalized with optical fiber, then another drug with antiproliferative capabilities can be delivered without functionalization with optical fiber, and then yet another drug with anti-inflammatory properties can be delivered to provide a valuable combination of beneficial drugs without compromise.

In addition, therapeutic agents that may be used with the devices of the present disclosure include any one or combination of several agents that are gases, liquids, suspensions, emulsions, or solids that may be delivered or collected from a blood vessel for therapeutic or diagnostic purposes. Therapeutic agents may include biologically active substances or substances capable of eliciting a biological response, including but not limited to endogenous substances (growth factors or cytokines including but not limited to basic fibroblast growth factor, acidic fibroblast growth factor, vascular endothelial growth factor, angiogenic factors, microRNA), viral vectors, DNA capable of expressing proteins, sustained release polymers, and unmodified or modified cells. The therapeutic agent may include an angiogenic agent that induces neovascularization. The therapeutic agent may also include an anti-stenosis or anti-restenosis agent for treating stenosis of the vessel wall. The therapeutic agent may include a photoactivator useful for treating vessel wall stenosis, such as a photoactivated anti-stenosis agent or a photoactivated anti-restenosis agent.

Thus, the device 100 is multifunctional, provides drug delivery control in both open and closed situations, and distracts the shaped vessel wall during drug functionalization with light sources of specific wavelengths outside the Ultraviolet (UV) range (10nm to 400 nm).

Another embodiment of the present disclosure includes an exemplary method of tissue repair in a blood vessel of a subject. The method may include positioning a catheter into a blood vessel. In some embodiments, the catheter may include the features of device 100 described above. For example, the catheter may include a catheter shaft (e.g., catheter shaft 104) extending from a proximal end (e.g., proximal end 106) to a distal tip (e.g., distal tip 110). A first distal balloon (e.g., first distal balloon 120) can be positioned on the catheter shaft adjacent the translucent distal section (e.g., distal section 130) of the distal tip, the first distal balloon in fluid communication with a drug source via a first lumen (e.g., first distal balloon inflation lumen 150). The first distal balloon may comprise a translucent material and be positioned within and concentric with a second distal balloon (e.g., second distal balloon 122), a plurality of longitudinal channels (e.g., longitudinal channels 124) being recessed from a plurality of outermost radial surfaces (e.g., outermost radial surface 127) of the first distal balloon, and a plurality of circumferential channels (e.g., circumferential fluid channels 126) being recessed from the outermost radial surface of the first distal balloon. The second distal balloon (e.g., second distal balloon 122) may be in fluid communication with a second lumen (e.g., second distal balloon inflation lumen 154) separate from the first lumen. The catheter may also include a first optical fiber (e.g., optical fiber 140) and a second optical fiber (e.g., optical fiber 142) each positioned in the catheter shaft and extending through the translucent distal section.

The method may further comprise: supplying a drug from a drug source to the first distal balloon; delivering the drug to the treatment area through the slit opening (e.g., slit opening 198); and activating the first and second optical fibers to provide light transmission through the distal section, the first distal balloon, and the second distal balloon to activate the drug in the treatment area. Light transmission to the treatment area may activate Natural Vascular Stent (NVS) that may be light activated. Expansion of the first distal balloon can shape the treatment area (e.g., blood vessel) as desired.

The method may further comprise: gradually filling a drug into volumes of longitudinal and circumferential channels between an inner surface of the second distal balloon and an outer surface of the first distal balloon; and inflating the second distal balloon, thereby moving the slit opening away from an outermost radial surface of the first distal balloon.

Thus, the devices and methods described herein provide for the delivery of NVS to a treatment area (e.g., a blood vessel) and repair of the treatment area using the device or according to the methods described above. The devices and methods described above simultaneously provide for treating the vessel with one or more drugs (e.g., using paclitaxel and NVS), supporting and casting the vessel, and photoactivating the one or more drugs delivered to the treatment area with minimal loss to other vessels. These advantages may be achieved using the devices and methods described herein.

According to embodiments of the present disclosure, NVS may include a dinaphthylimide, as described in U.S. patent No. 6,410,505B2 and U.S. provisional patent application No. 62/785,477. For example, a dinaphthylimide compound, 2,2' - ((ethane-1, 2-bis (oxy)) bis (ethane-2, 1-diyl) bis (6- ((2- (2- (2-aminoethoxy) ethyl) amino) -1H-benzo [ de ] isoquinoline-1, 3(2H) -dione), also known as 10-8-10 dimer, 6- [2- [2- (2-aminoethoxy) ethoxy ] ethylamino ] -2- [2- [2- [2- (2-aminoethoxy) ethoxy ] ethylamino ] -1, 3-dioxobenzo [ de ] isoquinolin-2-yl ] ethoxy ] benzo [ de ] isoquinoline-1, 3-diketones; 2,2' - [1, 2-ethanediylbis (oxy-2, 1-ethanediyl) ] bis [6- ({2- [2- (2-aminoethoxy) ethoxy ] ethyl } amino) -1H-benzo [ de ] isoquinoline-1, 3(2H) -dione ]; and 1H-benzo [ de ] isoquinoline-1, 3(2H) -dione, 2,2' - [1, 2-ethanediylbis (oxy-2, 1-ethanediyl) ] bis [6- [ [2- [2- (2-aminoethoxy) ethoxy ] ethyl ] amino ] - (9Cl), and in the above-mentioned patent application is intended to mean a compound of formula (I).

The foregoing description has been provided for the purposes of illustration. The foregoing description does not show all aspects and is not intended to limit the precise forms or embodiments disclosed herein. Modifications and variations to the embodiments disclosed herein will be apparent from consideration of the specification and practice of the embodiments disclosed herein. For example, the implementations include hardware and software, but systems and methods consistent with the present disclosure may be implemented solely as hardware. Additionally, although certain components have been described as being coupled to one another, such components may be integrated with or distributed across one another in any suitable manner.

Moreover, although illustrative embodiments have been described herein, the scope of the present invention includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations and/or alterations based on the present disclosure. The elements in the claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive. Further, the steps of the methods disclosed herein may be modified in any manner, including by reordering steps and/or inserting or deleting steps.

The features and advantages of the present disclosure will be apparent from the detailed description, and thus, it is intended by the appended claims to cover all such systems and methods which fall within the true spirit and scope of the present disclosure. As used herein, the indefinite articles "a" and "an" mean "one or more". Similarly, the use of plural terms does not necessarily refer to the plural unless explicitly stated in the context given. Words such as "and" or "mean" and/or "unless expressly indicated otherwise. Further, since numerous modifications and variations will readily occur to those skilled in the art, it is not desired to limit the disclosure to the exact construction and operation illustrated and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the disclosure (e.g., slit openings, apertures, perforations may be used interchangeably to maintain the true scope of the embodiments).

Other embodiments will be apparent from consideration of the specification and practice of the embodiments disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the embodiments disclosed herein being indicated by the following claims.

Claims (20)

1. An apparatus, comprising:

a catheter shaft extending from a proximal end to a distal tip;

a first distal balloon positioned on the catheter shaft proximal to the translucent distal section of the distal tip and positioned within and concentric with a second distal balloon, the first distal balloon in fluid communication with a drug source via a first lumen, the first distal balloon comprising:

a translucent material;

a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon;

a plurality of circumferential channels recessed from the outermost radial surface of the first distal balloon;

a second distal balloon in fluid communication with a second lumen separate from the first lumen; and

a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section.

2. The device of claim 1, wherein the second distal balloon includes a plurality of slit openings radially aligned with the outermost radial surface of the first distal balloon, the slit openings selectively delivering the drug from the first distal balloon to a treatment area of a subject.

3. The device of claim 2, wherein the slit opening is positioned distal to the longitudinal channel and the circumferential channel of the first distal balloon.

4. The device of claim 2, wherein the slit opening of the second distal balloon is held in contact with the outermost radial surface of the first distal balloon, thereby sealing the slit opening during inflation and deflation of the first distal balloon.

5. The apparatus of claim 2, wherein during inflation of the second distal balloon, the fluid fills between an inner surface of the second distal balloon and an outer surface of the first distal balloon, thereby gradually filling the longitudinal and circumferential channels.

6. The device of claim 5, wherein the pressure of the fluid between the inner surface of the second distal balloon and the outer surface of the first distal balloon increases and inflates the second distal balloon, the increased pressure forcing the edges of the slit opening apart, thereby reducing the pressure.

7. The device of claim 2, wherein inflation of the second distal balloon moves the slit opening away from the outermost radial surface of the first distal balloon, thereby allowing the slit opening to open and fluid to flow to the treatment area.

8. The device of claim 1, wherein the translucent materials of the distal section, the first distal balloon, and the second distal balloon are transparent.

9. The device of claim 1, wherein the first and second optical fibers provide light activation through the distal section, the first distal balloon, and the second distal balloon.

10. The device of claim 1, wherein the longitudinal channel and the circumferential channel are non-deformable and provide uniform drug delivery through the second distal balloon.

11. The device of claim 1, wherein the second distal balloon comprises a material conforming to a morphology of the blood vessel wall.

12. A method of tissue repair in a blood vessel of a subject, comprising:

disposing a catheter in the blood vessel, the catheter comprising:

a catheter shaft extending from a proximal end to a distal tip;

a first distal balloon positioned on the catheter shaft proximal to the translucent distal section of the distal tip and positioned within and concentric with a second distal balloon, the first distal balloon in fluid communication with a drug source via a first lumen, the first distal balloon comprising:

a translucent material;

a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon;

a plurality of circumferential channels recessed from the outermost radial surface of the first distal balloon;

a second distal balloon in fluid communication with a second lumen separate from the first lumen, the second distal balloon including a plurality of slit openings radially aligned with the outermost radial surface of the first distal balloon, the slit openings selectively delivering the drug from the first distal balloon to a treatment area of a subject; and

a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section;

supplying a drug from the drug source to the first distal balloon;

delivering the drug to the treatment area through the slit opening;

activating the first and second optical fibers to provide light transmission through the distal section, the first distal balloon, and the second distal balloon to activate the drug in the treatment area.

13. The method of claim 12, further comprising:

gradually filling the drug into the volumes of the longitudinal and circumferential channels between the inner surface of the second distal balloon and the outer surface of the first distal balloon;

inflating the second distal balloon, thereby moving the slit opening away from the outermost radial surface of the first distal balloon.

14. The method of claim 12, wherein the slit opening is positioned distal to the longitudinal channel and the circumferential channel of the first distal balloon.

15. The method of claim 12, further comprising deflating the second distal balloon when fluid is delivered through the slit opening.

16. The method of claim 15, wherein deflating the second distal balloon moves the second distal balloon into contact with the outermost radial surface of the first distal balloon and closes the slit opening, thereby causing cessation of drug delivery.

17. The method of claim 12, wherein the pressure of the fluid between the inner surface of the second distal balloon and the outer surface of the first distal balloon increases and inflates the second distal balloon, the increased pressure forcing edges of the slit opening apart, thereby reducing the pressure.

18. The method of claim 12, wherein the first and second optical fibers provide light activation through the distal section, the first distal balloon, and the second distal balloon.

19. The method of claim 12, wherein the slit opening is positioned distal to the longitudinal channel and the circumferential channel of the first distal balloon.

20. An apparatus, comprising:

a catheter shaft extending from a proximal end to a distal tip;

a first distal balloon positioned on the catheter shaft proximal to the translucent distal section of the distal tip and positioned within and concentric with a second distal balloon, the first distal balloon in fluid communication with a drug source via a first lumen, the first distal balloon comprising:

a translucent material;

a plurality of longitudinal channels recessed from a plurality of outermost radial surfaces of the first distal balloon;

a plurality of circumferential channels recessed from the outermost radial surface of the first distal balloon;

a second distal balloon in fluid communication with a second lumen separate from the first lumen; and

a first optical fiber and a second optical fiber each positioned in the catheter shaft and extending through the translucent distal section;

wherein the drug source is configured to provide at least one drug to the first distal balloon via the first lumen, and during inflation of the second distal balloon, the fluid fills between an inner surface of the second distal balloon and an outer surface of the first distal balloon, gradually filling the longitudinal channel and the circumferential channel.