Implantable catheter

Abstract

Various aspects of the present disclosure relate to devices, systems and methods configured to be implanted in a patient. These devices, systems and methods may include a catheter configured to be implanted in the intraperitoneal space of a patient, an internal flow lumen, and at least one opening connected to the internal flow lumen for delivering a therapeutic agent.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of Provisional Patent Application No. 62 / 878,130, filed on July 24, 2020, which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] The present disclosure relates generally to catheters, and more particularly to devices, systems, and methods including catheters implantable within a patient. Background Art

[0004] Catheters or other similar devices that are implanted for long periods of time may have issues with long-term patency. For example, depending on the location of implantation, catheters or other similar devices may cause physiological reactions such as foreign body reactions or inflammation. Such reactions may reduce the ability of the implanted catheter or other similar device to function as desired. Summary of the invention

[0005] According to one example ("Example 1"), a device configured to be implanted in a patient includes a catheter comprising a proximal segment and a distal segment configured to be implanted in the patient, an internal flow lumen, and at least one opening connected to the internal flow lumen for delivering a therapeutic agent; and a cover disposed around at least a portion of the distal segment and configured to reduce at least one of a foreign body response, inflammation, and cellular invasion, and to maintain the opening substantially unobstructed for drug delivery through the catheter.

[0006] According to another example ("Example 2") which is further relative to the apparatus of Example 1, the cover is an ePTFE (thin) film.

[0007] According to another example ("Example 3") further relative to the apparatus of any of Examples 1-2, the cover extends between about 1 mm and about 100 mm from the distal end of the catheter along the portion of the distal section.

[0008] According to another example ("Example 4") further relative to the apparatus of any of Examples 1-3, the catheter is configured for delivering a drug to the intraperitoneal space through the internal flow lumen, and the cover includes a drug dispensing material.

[0009] According to another example ("Example 5") further than the apparatus of Example 4, the catheter is an indwelling catheter configured to be implanted in the intraperitoneal space for up to 20 years.

[0010] According to another example ("Example 6") further relative to the apparatus of any one of Examples 1-5, at least one opening is disposed at a distal end of the catheter.

[0011] According to another example ("Example 7") further relative to the apparatus of any of Examples 1-6, the at least one opening includes a plurality of openings spaced around a circumference of the distal section of the catheter to enable uniform distribution of the therapeutic agent.

[0012] According to another example ("Example 8") further relative to the apparatus of Example 7, a cover is disposed over the plurality of openings.

[0013] According to another example ("Example 9") further than the apparatus of any one of Examples 1-8, the apparatus further includes a sealing tip disposed at the distal end of the catheter.

[0014] According to another example ("Example 10") further than the device of Examples 1-9, the device also includes an inner layer disposed within the catheter along the inner flow lumen, the inner layer being configured to reduce foreign body reaction and inflammation.

[0015] According to another example ("Example 11") further than the apparatus of any of Examples 1-10, the apparatus further includes at least one of a bioactive agent or a bioactive covering disposed on an outer surface of the catheter.

[0016] According to another example ("Example 12") further relative to the apparatus of any of Examples 1-11, the apparatus also includes a self-closing tube segment disposed at the distal end of the elongated body.

[0017] According to another example ("Example 13") further than the apparatus of Example 12, the self-closing tube segment is configured to open in response to pressure from a pump forcing a therapeutic agent through the elongated body, and to close in response to the absence of that pressure (absence of that pressure).

[0018] According to another example ("Example 14") that is further than the device of any of Examples 1-11, the device also includes a catheter end segment disposed at the distal end of the slender body, the catheter end segment including a valve configured to open in response to pressure from a pump forcing a therapeutic agent through the slender body and to close in response to the absence of such pressure.

[0019] According to another example ("Example 15") that is further than the device of any of Examples 1-11, the device also includes a pressure-expanded elastomeric tip disposed at the distal end of the slender body, the elastomeric tip including an opening configured to open in response to pressure from a pump forcing a therapeutic agent through the slender body, and to close in response to the absence of pressure.

[0020] According to one example ("Example 16"), a treatment method includes providing a catheter comprising a proximal segment, a distal segment, an internal flow lumen, and at least one opening connected to the internal flow lumen for a therapeutic agent disposed at the distal end of the catheter; inserting the distal end of the catheter into a patient; and introducing a therapeutic agent into the internal flow lumen, thereby delivering the therapeutic agent into the patient through the at least one opening.

[0021] According to another example ("Example 17") that is further than the method of Example 16, the catheter also includes a covering that is disposed around at least a portion of the distal segment and is configured to reduce at least one of foreign body reaction, inflammation, and cellular invasion and maintain the opening substantially unobstructed for delivery of the therapeutic agent through the catheter.

[0022] According to another example ("Example 18") further than the method of Example 17, the cover is made of an ePTFE film.

[0023] According to another example ("Example 19") further than the method of Examples 17-18, the cover extends between about 1 mm and about 100 mm from the distal end of the catheter along the portion of the distal section.

[0024] According to another example ("Example 20") further relative to the methods of Examples 16-19, the at least one opening includes a plurality of openings spaced around a circumference of the distal section of the catheter to enable uniform distribution of the therapeutic agent.

[0025] According to another example ("Example 21") further relative to the methods of Examples 16-20, the method also includes a step of controlling the flow of therapeutic agent delivery with a pump.

[0026] According to another example ("Example 22") further than the methods of Examples 16-21, the therapeutic agent includes insulin.

[0027] The foregoing examples are merely examples and should not be construed as limiting or otherwise narrowing the scope of any inventive concept otherwise provided by the present disclosure. Although a number of examples are disclosed, other examples will become apparent to those skilled in the art from the following detailed description, which illustrates and describes illustrative examples of the present invention. Therefore, the drawings and detailed description should be considered illustrative in nature and not restrictive in nature. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The accompanying drawings are included to provide a further understanding of the disclosure and are incorporated in and constitute a part of this specification, illustrate embodiments and together with the description serve to explain the principles of the disclosure.

[0029] Figure 1is an example catheter system disposed within a patient according to various aspects of the present disclosure.

[0030] Figure 2 is an example catheter for implantation in a patient according to various aspects of the present disclosure.

[0031] Figure 3 is another example catheter for implantation in a patient according to various aspects of the present disclosure.

[0032] Figure 4 is another example catheter for implantation in a patient according to various aspects of the present disclosure.

[0033] Figure 5 is another example catheter for implantation in a patient according to various aspects of the present disclosure.

[0034] Figure 6 is another example catheter for implantation in a patient according to aspects of the present disclosure.

[0035] Figure 7 is another example catheter for implantation in a patient according to various aspects of the present disclosure.

[0036] Figure 8 are example catheter tips according to various aspects of the present disclosure.

[0037] Fig. 9 is another example catheter tip according to various aspects of the present disclosure.

[0038] Fig.10 is yet another example catheter tip according to various aspects of the present disclosure.

[0039] Fig.11A is an example catheter tip in a first configuration according to various aspects of the present disclosure.

[0040] Fig. 11B According to various aspects of the present disclosure, the second configuration Fig.11A Example catheter tip shown in .

[0041] Fig.12 is another example catheter tip according to various aspects of the present disclosure.

[0042] Fig.13 is another example catheter tip according to various aspects of the present disclosure. DETAILED DESCRIPTION

[0043] Definitions and terminology

[0044] As used herein with respect to ranges of measurements, the terms “about” and “approximately” are used interchangeably to refer to measurements that include the measurement and also include any measurement that is reasonably close to the measurement but that may differ by a reasonably small amount, which may be attributable to measurement errors, differences in calibration of measurement and / or manufacturing equipment, human errors in reading and / or setting measurements, adjustments to optimize performance and / or structural parameters to account for differences in measurements associated with other components, specific implementation scenarios, inaccurate adjustment and / or manipulation of objects by humans or machines, etc., as would be understood and readily determined by a person of ordinary skill in the relevant art.

[0045] This disclosure is not intended to be read in a limiting manner.For example, the terms used in this application should be read broadly in the context of the meaning that one skilled in the art would attribute to such terms.

[0046] With respect to imprecise terms, the terms "about" and "approximately" are used interchangeably to refer to measurements that include the stated measurement, and also include any measurements that are reasonably close to the stated measurement. As understood and readily determined by one of ordinary skill in the relevant art, measurements that are reasonably close to the stated measurement deviate from the stated measurement by a relatively small amount. For example, such deviations may be due to measurement error or minor adjustments made to optimize performance. If it is determined that a person of ordinary skill in the relevant art would not easily determine a value for such a relatively small difference, the terms "about" and "approximately" may be understood to be the stated value plus or minus 10%.

[0047] Description of various embodiments

[0048] Those skilled in the art will readily appreciate that various aspects of the present disclosure may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the drawings referenced herein are not all drawn to scale, but may be enlarged to illustrate various aspects of the present application, and in this regard, the drawings should not be construed as limiting. It should be noted that the terms "catheter system" and "system" are used interchangeably herein.

[0049] Various aspects of the present disclosure relate to devices, systems and methods including catheters configured to be implanted in a patient. The catheter may include one or more outer layers that mitigate the physiological response that occurs when a foreign body or device is implanted in the intraperitoneal space. In some cases, the physiological response may reduce the ability of the catheter to function as intended. As discussed in further detail below, the catheter mitigates the physiological response to maintain the function of the catheter.

[0050] Figure 11 is an example of a catheter system 100 disposed within an intraperitoneal space 102 of a patient 104 in accordance with various aspects of the present disclosure. The intraperitoneal space 102 is located between the muscles and organs of the abdomen and includes a peritoneal lining, wherein body fluid is present between the peritoneal lining and the organs. In some cases, when a large amount of blood replacement fluid is required, or when hypotension or other clinical and / or surgical complications prevent the use of a suitable blood vessel for intravenous administration, it may be preferable to use intraperitoneal therapy rather than such intravenous administration. As a more direct physiological approach, and therefore providing a potentially superior response to treatment, intraperitoneal therapy may also be preferred over subcutaneous therapy.

[0051] The system 100 for intraperitoneal treatment may include an access port 106 and a catheter 108 in fluid communication with the access port 106. The access port 106 may be placed in a pocket formed under the skin within the subcutaneous tissue of the patient's 104 body (e.g., within the lower or upper abdomen), and the catheter extends from the access port 106 into the peritoneal space 102. In the illustrative embodiment, the catheter 108 is a thin (thin) flexible tube composed of silicone or other compliant polymers.

[0052] During intraperitoneal treatment, agents, medications, fluid products, nutrients, and / or another therapeutic agent may be mixed with the fluid and injected directly into the peritoneal space 102 through the access port 106 and the catheter 108. In some embodiments, a pump 118 may be used with the catheter system 100, which includes a reservoir that maintains a supply of a therapeutic agent (e.g., an agent or a fluid) to the catheter 108 on a controlled basis. A monitor may also be used in conjunction with the catheter system 100. In other embodiments, the catheter 108 may be placed in other spaces of the body (e.g., the lower back) to conduct treatment.

[0053] In some cases, pump 118 can be implanted in a subcutaneous area (e.g., beneath the skin). Pump 118 can be configured to release a drug or therapeutic agent into the intraperitoneal cavity (e.g., in a manner similar to that described in the literature). Figure 6 and Figure 7 at the biological interface of the distribution material).

[0054] like Figure 1As shown, the catheter 108 includes a proximal section 112 near the entry port 106 and includes a distal section 114. At least the distal section 114 is configured to be implanted in the intraperitoneal space 102 of the patient 104. The catheter 108 includes an elongated body 116 that is generally formed in a cylindrical shape, but other shapes can be used and these shapes are considered to be within the scope of the present invention. For example, the catheter 108 can be formed into a shape representing any number of different polygons or other shapes, such as those utilizing curved portions. The elongated body 116 of the catheter 108 forms an internal flow lumen that enables fluid contact with at least one opening in the elongated body 116 that is connected to the internal flow lumen to deliver medicine, fluid products, nutrients and / or another therapeutic agent. In some cases, the catheter 108 can be used to collect fluid or sample the fluid.

[0055] For example, the elongated body 116 of the catheter 108 may also define an opening at the proximal end 130 of the proximal section 112 of the catheter 108 or the distal end 128 of the distal section 114, which is directly connected to the internal flow lumen of the catheter 108 to provide access to the internal flow lumen and the intraperitoneal space 102 for delivery of therapeutic agents that may include drugs or other therapeutic agents. In some cases, the distal end 128 may be a portion of the catheter 108 exposed to the intraperitoneal space. In an illustrative embodiment, a covering (extraluminal and / or intraluminal) may be provided around at least a portion of the distal section 114 of the catheter 108 to mitigate foreign body reactions or inflammation that may occur due to insertion of the catheter 108 into the patient 104, as discussed further below. Such a covering may additionally maintain the opening at the distal end 128 of the catheter 108 substantially unobstructed to facilitate delivery of therapeutic agents that may include drugs or other therapeutic agents through the catheter 108. The lumen of catheter 108 may also be coated with an active ingredient such as heparin, which may reduce foreign body reaction. Catheter 108 may be soft (eg, tissue compliant) and flexible to maintain compliance and patient 104 comfort without kinking and / or to minimize tissue irritation.

[0056] Figure 22 is an example catheter system 208 for implantation in a patient according to various aspects of the present disclosure. In some cases, the catheter 208 includes a silicone elongated body 116 that defines an inner flow lumen 220. In other embodiments, the elongated body 116 of the catheter 208 may include other polymers such as polyurethane. The wall of the inner flow lumen 220 may include or be coated with a polymer layer. In some cases, the polymer layer may prevent changes in the pH value of the drug or other therapeutic agent to be delivered. For example, the wall of the inner flow lumen 220 of the catheter 208 may include a polyethylene layer or be otherwise coated with polyethylene, which serves as a barrier to prevent carbon dioxide from penetrating from the environment surrounding the catheter to maintain (or otherwise not affect) the pH balance of insulin delivered to the intraperitoneal space of a diabetic patient. In other cases, other polymers or hydrophilic materials corresponding to the therapeutic agent used in the treatment may be used. The walls (and / or outer surfaces) of the elongated body 116 and the inner flow lumen 220 may also be coated with heparin, dexamethasone, or another bioactive agent to minimize fibrotic cell encapsulation within or around the catheter 208 .

[0057] In some cases, the catheter 208 may also include a covering 222 configured to cover substantially the entire elongated body 116 of the catheter 208. The covering 222 may include a fluoropolymer, such as polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE). In some cases, the inner flow lumen 220 may also include a layer of a fluoropolymer or be coated with a fluoropolymer, such as PTFE or ePTFE. The covering 222 may be bonded to the catheter 208 by an adhesive, such as liquid silicone rubber or another biocompatible polymer adhesive. The liquid silicone rubber or other adhesive may be applied to the covering 222 or the elongated body 116 of the catheter 208, and then the sleeve wrapped around the elongated body 116 of the catheter 208, so that the adhesive forms a bond between the covering 222 and the elongated body 116.

[0058] The catheter 208 includes a Figure 1 The proximal section 112 of the access port 106 is shown and the distal section 114 can be implanted into the intraperitoneal space 102 of the patient 104. The distal section 114 of the catheter 208 is Figure 2. The catheter 208 (or the distal section of the catheter 208) can be configured to remain in the intraperitoneal space 102 of the patient 104 for any period of time including several years and up to 20 years (e.g., unless infected or ineffective). In other cases, the catheter 208 can remain in the intraperitoneal space of the patient 104 for a shorter or longer period of time. The elongated body 116 of the catheter 208 can be formed into a cylindrical shape, but other shapes can be used. The elongated body 116 forms an inner flow lumen 220 that enables fluid contact with at least one opening connected to the inner flow lumen 220 to deliver drugs, fluid products, nutrients, or (one or more) other therapeutic agents.

[0059] For example, the elongated body 116 of the catheter 208 may also include an opening 126 at the distal end 128 of the distal segment 114 of the catheter 208 that is directly connected to the internal flow lumen 220 of the catheter 208 to provide an exit point for the internal flow lumen 220 to enter the intraperitoneal space for delivery of a therapeutic agent that may include a drug or (one or more) other therapeutic agents.

[0060] The covering 222 disposed about the outer surface of the elongated body 116 of the catheter 208 can be configured to reduce foreign body reactions or inflammation that may occur as a result of implanting the catheter 208 into a patient. The covering 222 can additionally maintain a substantially unobstructed opening 126 at the distal end 128 of the catheter 208 to facilitate delivery of a fluid, which may include a drug or therapeutic agent, through the inner flow lumen 220 of the catheter 208. In some cases, the catheter 208 can include an additional cannula disposed within the inner flow lumen 220 of the catheter 208. The cannula can further reduce foreign body reactions, reduce further fibrotic encapsulation, or reduce inflammation within the catheter 208. Additionally, the elongated body 116 of the catheter 208 can be coated with a bioactive agent to further prevent fibrotic cell encapsulation, flow obstruction to the therapeutic agent, or other adverse effects of catheter insertion into the intraperitoneal space of a patient.

[0061] In some cases, the microstructure of the cover 222 is configured to reduce the possibility of fibrotic encapsulation. In some cases, the open porous microstructure of the cover 222 is designed to allow and / or promote cell ingrowth and / or reduce the possibility of fibrotic encapsulation. In other cases, an ePTFE structure (a compact structure) with small nodes and short fibrils can be used as a porous microstructure to prevent fibrotic encapsulation. In some cases, the cover 222 allows a therapeutic agent, which may include a drug or another therapeutic agent, to flow out continuously, and the therapeutic agent is taken up by the tissue surrounding the catheter 208. In other cases, the cover 222 may include another biocompatible material (additionally or alternatively) that is configured to inhibit or otherwise prevent fibrotic encapsulation while enabling continuous outflow from the catheter.

[0062] Figure 3 2 is another example catheter 308 for implantation in a patient according to various aspects of the present disclosure. The catheter 308 may share many features of the catheters 108, 208 described above, including the elongated body 116, the inner flow lumen 220, the proximal section 112, and the distal section 114.

[0063] The catheter 308 may also include a distal cover 324 that covers a portion of the distal section 114 of the catheter 308 adjacent to the opening 126. In some cases, the distal cover 324 includes a fluoropolymer, such as polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE). In addition, the distal cover 324 may include an ePTFE septum cap that inhibits cell infiltration and minimizes inflammatory / fibrotic encapsulation while enabling continuous outflow of the therapeutic agent. In some cases, the distal cover 324 may include an ePTFE septum cap having an outer surface layer and an inner surface layer, the outer surface layer having a microporous structure that is designed to minimize foreign body reaction, and the inner surface layer having a microstructure that is configured to act as a filtering membrane and prevent cells from invading the lumen of the catheter 308 and allow the therapeutic agent to be transported out of the catheter 308 into the surrounding tissue.

[0064] The cover 324 may be bonded to the catheter 308 by an adhesive, such as liquid silicone rubber or another biocompatible polymer adhesive. In some cases, the liquid silicone rubber or another adhesive may be applied to the cover 324 or the elongated body 116 of the catheter 308, and then the cannula is placed in contact with the elongated body 116 at the bonding point so that the adhesive forms a bond between the cover 324 and the elongated body 116 while allowing the cover 324 to maintain the opening 126 of the distal end 128 of the distal section 114 of the catheter 308 unobstructed. The cover 324 may extend from about 1 mm to about 100 mm along the distal section 114 from the distal end 128 of the catheter 308. In some cases, the cover 324 may extend the entire length of the catheter 308. In some cases, the cover 324 may extend about 5%-25% of the length of the catheter 308 along the distal section 114.

[0065] like Figure 1 As shown, the proximal section 112 of the catheter 308 can be coupled to the access port 106, and the distal section 114 of the catheter 308 can be implanted within the intraperitoneal space 102 of the patient 104. In some cases, the catheter 308 can remain in the intraperitoneal space 102 of the patient 104 for any period of time across the life of the catheter. The elongated body 116 has an inner flow lumen 220 that enables fluid contact or fluid communication with at least one opening connected to the inner flow lumen 220 to deliver drugs, fluid products, nutrients, or liquids.

[0066] The cover 324 disposed around at least a portion of the distal section 114 of the catheter 308 is configured to reduce foreign body reactions or inflammation that may occur due to implantation of the catheter 308 into the patient's body. In some cases, the cover 324 can extend along the distal portion 114 of the catheter 308 and wrap around the distal end 226 and into the internal flow lumen 220 to cover or coat a portion of the internal flow lumen 220. An additional cover 324 can be coupled to the catheter 308 or disposed within the catheter 308 along the internal flow lumen 220. In some cases, this additional cover 324 can further reduce foreign body reactions or inflammation (e.g., caused by insertion of the catheter 308 into the body of the patient 104). In addition, the elongated body 116 of the catheter 308 can be coated with a bioactive agent to prevent fibrotic cell encapsulation or other adverse effects of catheter insertion.

[0067] Figure 4 FIG. 4 is another example catheter 408 for implantation in a patient according to various aspects of the present disclosure. Figure 4 As shown, the distal end 128 of the catheter 408 may include a sealing tip 432. The sealing tip 432 may be spherical, flat, rounded, or polygonal. The sealing tip 432 closes the catheter 408, and therefore, the catheter 408 includes an opening 434 along the elongated body 116 and in contact with the internal flow lumen 220 to enable the therapeutic agent to be dispersed. In some cases, the openings 434 are spaced apart in the distal section 114 of the catheter 408 to enable the therapeutic agent (e.g., an agent or liquid) to be dispersed in the intraperitoneal space. In some cases, a plurality of openings 434 are spaced apart around the periphery of the distal section 114 of the catheter 408 to achieve uniform distribution of the therapeutic agent. In other cases, the openings 434 may exist substantially along the entire catheter 408.

[0068] like Figure 4 As shown, the openings 434 can be drilled, formed, pierced, or otherwise made to pass through the elongated body 116 in a radial arrangement. Other arrangements of the openings 434 can be used, and other methods can be used to form the openings 434 in the elongated body 416. The openings 434 are not limited to Figure 4 The catheter 408 shown can also be used with Figure 1-3 The catheter 108 shown is used in conjunction with the Figure 1-3 The catheter 108 shown in FIG. 1 may also include a catheter similar to Figure 4 The sealed end of the sealed end 432 shown in .

[0069] The catheter 408 also includes a cover 222 that covers at least the opening 434 in the distal section 114 of the catheter 408. In an illustrative embodiment, the cover 222 includes a semi-permeable material (e.g., ePTFE) that inhibits fibrotic cell infiltration while allowing the therapeutic agent to flow out continuously. In some cases, the microstructure of the cover 222 is controlled to inhibit cell infiltration while maintaining semi-permeability to various therapeutic agents. For example, the cover 222 with an ePTFE structure may include nodes with fibrils to provide a semi-permeable microstructure in which the pores are large enough to allow drug molecules to flow, insulin to disperse, or other therapeutic agents to disperse and cause the microstructure to be open enough to allow such dispersion. The cover 222 can enable the therapeutic agent to flow out continuously and be taken up by the tissue around the catheter 408. In other cases, the cover 222 can enable the new blood vessels of the blood vessels to grow into its porous structure, thereby reducing the distance between the delivery and uptake of the therapeutic agent and minimizing the delay time. In other cases, the cover 222 can provide a structure that blocks cell invasion while maintaining unimpeded outflow of the therapeutic agent. In other cases, the cover 222 can be composed of another biocompatible material that is configured to inhibit or otherwise prevent cell infiltration and fibrotic encapsulation while achieving continuous outflow.

[0070] As described in detail above, the catheter 408 can be coupled to Figure 1 Access port 106 is shown, and distal section 114 of catheter 408 may be implanted within intraperitoneal space 102 of patient 104 .

[0071] Figure 4 The conduit 408 shown in FIG. 4 is provided as an example of various features of the cover 222, and while combinations of those features shown are clearly within the scope of the present disclosure, this example and its illustration are not meant to imply that the inventive concepts provided herein are limited to combinations from fewer features, additional features, or alternative features. Figure 4 One or more of those features shown. For example, in various embodiments, Figure 4 The catheter 408 shown in FIG. 4 may include reference Figure 3 The distal cover 324 described above. It should also be understood that the reverse is also true. Figure 4 One or more of the components depicted in the drawings may be employed in addition to or in place of components shown in other figures. For example, the cover 222 discussed herein may include the microstructural features discussed in detail above.

[0072] Figure 5 508 is another example catheter for implantation in a patient according to various aspects of the present disclosure. The catheter 508 may share many features of the catheter 408 described above, including the elongated body 116, the inner flow lumen 220, the proximal section 112, and the distal section 114.

[0073] The catheter 508 also includes a cover 222. In the illustrated embodiment, the cover 222 (e.g., Figure 4 or Figure 5 The cover 222 may include a semi-permeable material (e.g., ePTFE) that inhibits fibrotic cell infiltration while enabling continuous outflow of therapeutic agents. In some cases, the microstructure of the cover 222 is controlled to inhibit fibrotic cell infiltration while maintaining semi-permeability to various therapeutic agents. For example, the cover 222 having an ePTFE structure may include nodes with fibrils to provide a semi-permeable microstructure (e.g., permeable to particles or elements of certain sizes, but impermeable to particles or elements of other sizes), in which the pores are large enough to allow bulk flow of drug molecules, dispersion of insulin or other therapeutic agents and cause the microstructure to be open enough to allow such dispersion. The cover 222 may enable the therapeutic agent to continuously outflow and be taken up by the tissue surrounding the catheter 508. In other cases, the cover 222 may be made of another biocompatible material that is configured to inhibit or otherwise prevent fibrotic encapsulation while achieving continuous outflow through the distal cover 324.

[0074] The catheter 508 may also include a distal cover 324 that covers a portion of the distal section 114 of the catheter 508 adjacent to the opening 126. In some cases, the distal cover 324 includes a fluoropolymer, such as PTFE or ePTFE. In addition, the distal cover 324 may include an ePTFE septum cap that inhibits fibrotic cell infiltration and minimizes inflammation / fibrosis encapsulation while enabling continuous outflow of the therapeutic agent. For example, the distal cover 324 having an ePTFE structure may include nodes and have fibrils to provide a semi-permeable microstructure (e.g., permeable to particles or elements of certain sizes, but impermeable to particles or elements of other sizes), in which the pores are large enough to allow the volume flow of drug molecules, the dispersion of insulin or other therapeutic agents and cause the microstructure to be open enough to allow such dispersion, while also having small enough pores that will prevent cell invasion. The distal cover 324 can enable continuous outflow of the therapeutic agent and allow the tissue surrounding the catheter 508 to absorb the therapeutic agent.

[0075] To reduce foreign body reaction, inflammation and maintain the opening substantially unimpeded for drug delivery through catheter 508, distal cover 324 and / or elongated body cover 222 may be formed of ePTFE, the permeability and ability to promote mesothelial cell ingrowth of which is determined by the pore size and material thickness. The pore size is measured at the surface of the material by determining the internode distance or fibril length of the material. The fibril length can be measured as described in U.S. Patent No. 4,482,516. The ePTFE fibril length along a single direction or along more than one direction is estimated as the average of several measurements between nodes connected by fibrils along various orientations of stretching. Cover 324 and cover 222 may have different permeabilities.

[0076] The fibril length and thickness of the ePTFE material are selected to resist or accept cell ingrowth across a portion of the elongated body 116 of the catheter 508 or across its entire length and / or thickness (e.g., corresponding to the location of the cover 324 and / or the cover 222). The structure of the elongated body 116 of the catheter 508 can be a laminated material with variable permeability (e.g., with sections of different permeabilities), such as a cell permeable layer adjacent to the outer surface of the catheter and a cell repellent layer adjacent to the internal flow lumen 220. The cell permeable layer and the cell repellent layer of the catheter 508 can each occupy an equal or asymmetric proportion of the total thickness of the catheter wall construction, with the thickness of each material ranging from 1 micron to about 2500 microns.

[0077] The cell permeable layer may have an average pore size greater than about 3.0 microns, and in some cases, the pore size may be greater than about 5.0 microns. The cell exclusion layer is impermeable to cell ingrowth, preventing cells from entering the inner flow lumen 220 and contacting, adhering to, scaling, ingrowing, overgrowing, or otherwise interfering with the therapeutic agent or drug delivered through the conduit 508. To exclude invading host cells, the average pore size of the exclusion layer may range from less than about 3.0 microns to 0.1 microns.

[0078] Figure 5 The conduit 508 shown in FIG. 5 is provided as an example of various features of the cover 324 and / or the cover 222, and while combinations of those features shown are clearly within the scope of the present disclosure, the example and its illustration are not meant to imply that the inventive concepts provided herein are limited to combinations from fewer features, additional features, or alternative features. Figure 5 One or more of those features shown. For example, in various embodiments, Figure 5 The catheter 508 shown in FIG. 5 may include reference Figure 4 The radial opening 434 described above. It should also be understood that the reverse is also true. Figure 5One or more of the components depicted in the drawings may be employed in addition to or in place of components shown in other figures. For example, the cover 222 discussed herein may include the microstructural features discussed in detail above.

[0079] Figure 6 6 is another example catheter 608 for implantation in a patient according to various aspects of the present disclosure. The catheter 608 may share many features of the catheter 508 described above, including the elongated body 116, the inner flow lumen 220, the proximal section 112, and the distal section 114. The elongated body 116 of the catheter 108 may also define an opening at the proximal end 130 of the proximal section 112 of the catheter 108 or the distal end 128 of the distal section 114, the opening being directly connected to the inner flow lumen of the catheter 108 to provide access to the inner flow lumen and the intraperitoneal space 102 for delivery of therapeutic agents that may include drugs or other therapeutic agents.

[0080] The catheter 608 may also include a distal cover 324 that covers a portion of the distal section 114 of the catheter 608 adjacent to the opening 126. In some cases, the distal cover 324 is configured to facilitate distribution of a therapeutic agent or drug delivered through the catheter 608. Figure 6 , Figure 7 is another example catheter 708 for implantation in a patient according to various aspects of the present disclosure, the catheter including a distal cover 324 configured to facilitate distribution of a therapeutic agent or drug delivered through the catheter 708 . Figure 7 The distal cover 324 is or includes a drug dispensing leaflet. The distal cover 324 including the dispensing properties may be kink resistant and may be collapsible to eliminate dead volume. The leaflets may be made of a drug dispensing material for therapeutic administration in a wide range of blood and lymphatic capillaries. The catheter 608 and the catheter 708 may be coupled to the pump 118 described in detail above to drive the therapeutic agent or drug for delivery.

[0081] In some cases, the cover 324 configured as a drug dispensing material can disperse the therapeutic agent or drug over a wide biological area by wicking or other dispersion methods. Such dispersion methods can facilitate access to a large number of blood or capillary lymphatic vessels within the host tissue and achieve natural pharmacokinetics, thereby producing a more benign healing response.

[0082] The cover 324 configured as a drug dispensing material may integrate a microstructure comprising a fibrillated polymeric material (e.g., fluoropolymers, thin ePTFE membranes, composite membranes, and bioabsorbable substrates) that exhibits selective permeability to help establish an interface between the therapeutic agent or drug and surrounding body fluids, dissolved gases, or gases that may otherwise alter the properties of the drug. In some cases, the cover 324 may include a fibrillated polymer diffusion material configured to exhibit permeability to macromolecules having a molecular weight consistent with the target clinical application. In some cases, the fibrillated fabric may be constructed by its thickness, pore size, fibril length, and orientation of the classified fibrils. Fluid transport through the fibrillated polymer fabric may correspond to a random distribution of the therapeutic agent or drug.

[0083] In some cases, the cover 324 may include at least a portion having a variable porosity across the length or thickness of the cover 324. Fluid transport can be controlled by producing fibrils with higher or lower density and / or with significantly fewer or more node numbers. In some cases, the cover 324 can be controlled by producing a fibrillated material with a channel with a gradually changing size, which is reduced or increased. In some cases, the narrowest channel size at the front end of the distribution material prevents cell invasion. In some cases, the pore size of the cover 324 may be smaller than the size of a nucleated cell (e.g., about 8 to about 20 microns), the size of an erythrocyte (e.g., about 8 microns), and the size of a platelet (e.g., about 2 microns).

[0084] The cover 324 configured as a drug distribution material can help the therapeutic agent or drug diffuse into the intraperitoneal cavity to reach equilibrium. The rate of fluid exchange can be controlled by concentration gradients and / or by the number of pores opened for exchange (e.g., the porosity of the distribution material). In some cases, the structural features of the distribution material can provide an increased surface area, resulting in increased permeability for the fluid exchange of diffusion. The porous material portion at the biological interface is permeable to the passive diffusion of solutes (therapeutic molecules). In some cases, the structure of the material (e.g., fibrils and pore density) can be configured to apply resistance to solution discharge at the exchange interface with host tissue.

[0085] In some cases, restricted fluid movement due to boundary conditions may be affected by biological activity at the interface between the diffusion material and the tissue. The cover 324, which is configured as a drug distribution material, can be configured to facilitate biological interface to deliver therapeutic solutes to the interstitial fluid and capillaries without hindrance. In addition, the cover 324 can be configured to support host tissue anchoring, capillary growth, while minimizing foreign body entrapment or chronic inflammation. In other cases, the cover can be composed of a dense and porous material or material composite that minimizes cell invasion while allowing the outflow of therapeutic agents.

[0086] The cover 324 configured as a drug dispensing material may include free space and fenestrations within the diffusion material. The free space and fenestrations of the cover 324 may minimize dead space and optimize fluid delivery. In some cases, the drug dispensing material may be collapsible, may be a collapsible tube, or include a conduit 608, 708 that may be collapsible. For example, the conduit 808 (or any conduit discussed herein) may include a self-collapsible elongated body 116 composed of a self-collapsible composite material such as a porous ePTFE-elastomer (e.g., silicone or polyurethane) composite.

[0087] The self-collapsible elongated body 116 can be configured to collapse onto itself when no therapeutic agent is injected therethrough. The self-collapsible elongated body 116 collapsed onto itself seals the inner flow lumen 220 of the catheter and prevents or minimizes cell infiltration from the intraperitoneal space and a foreign body reaction cascade within the lumen 200. As described in detail above, the proximal section 112 of the catheter 808 can be attached to an implantable pump for delivering a therapeutic agent. When pump pressure is applied to deliver the therapeutic agent, the self-collapsible elongated body 116 expands (and can also stretch), thereby opening the inner flow lumen 220 for delivery of the therapeutic agent through the distal end 114. The expansion and / or stretching of the self-collapsible elongated body 116 under the action of the pump pressure can further detach any cells or organic deposits that may have infiltrated the lumen from the inner wall of the self-collapsible elongated body 116.

[0088] In some cases, the cover 324 configured as a drug distribution material can be configured to facilitate tissue anchoring and additionally prevent invasive cells from colonizing the material (e.g., macrophage contamination) or otherwise interfering with the release of the therapeutic agent. In some cases and as described in detail above, the distribution material can be ePTFE, which is configured to minimize or regulate fibrous capsule formation and establish a complete or partial barrier to biological tissues and cells. In some cases, a portion of the local barrier can also limit the penetration of body fluids such as blood, interstitial fluid, dissolved substances or gases.

[0089] In addition, the inner wall of the elongated body 116 may include or be coated with a polymer layer, or another polymer layer may be included in the wall. In some cases, the polymer layer can prevent the pH value of the drug or other therapeutic agent to be delivered from changing. For example, the wall of the inner flow lumen 220 of the catheter 808 may include a polyethylene layer or be otherwise coated with polyethylene, which is used as a barrier to prevent carbon dioxide from penetrating from the surrounding environment of the catheter to maintain (or otherwise not affect) the pH balance of insulin delivered to the intraperitoneal space of the diabetic patient. In other cases, other polymers or hydrophilic materials corresponding to the therapeutic agent used in the treatment can be used. The wall (and / or outer surface) of the elongated body 116 and the inner flow lumen 220 may also be coated with heparin, dexamethasone or another bioactive agent to minimize the foreign body reaction of the fibrotic cell encapsulation around the catheter or the inside of the catheter 808.

[0090] Figure 8 800 is an example catheter tip 800 according to various aspects of the present disclosure. The catheter tip 800 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 800.

[0091] As shown, catheter end 800 can be a pressure relief valve. In some cases, catheter end 800 is configured as a self-closing tube segment 802. The self-closing tube segment 802 of catheter end 800 can be opened in response to the pressure from a pump, and this pressure forces the therapeutic agent to pass through the catheter connected by catheter end 800. The self-closing tube segment 802 of catheter end 800 can be formed by porous ePTFE-elastomer (for example, silicone or polyurethane) compound. In some cases, the self-closing tube segment 802 of catheter end 800 can be formed by a silicone tube enhanced by ePTFE. For further discussion about the exemplary formation of the self-closing tube segment 802, reference can be made to U.S. Patent No. 9,849,629, which is granted to Zaggl et al., and is incorporated herein by reference.

[0092] Fig. 9 is another example catheter tip 900 according to various aspects of the present disclosure. The catheter tip 900 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 900.

[0093] In some cases, the catheter end 900 is configured as a duckbill section 902. The duckbill section 902 of the catheter end 900 can be opened in response to pressure from a pump, which forces the therapeutic agent through the catheter to which the catheter end 900 is connected. The pressure from the pump can open the duckbill section 902 and close the duckbill section 902 in response to the release of pressure or in response to the absence of pressure. The actuation or opening / closing of the duckbill section 902 can help alleviate any foreign body reaction, inflammation or cell entry deposits, and maintain the opening substantially unimpeded for drug delivery through the catheter. The duckbill section 902 can be formed by pinching or by forming the end of the tube by liquid silicone injected into a mold. In other cases, the duckbill section 902 can be formed by an ePTFE / silicone composite tube on a mandrel.

[0094] Fig.10 22 is yet another example catheter tip 1000 according to various aspects of the present disclosure. The catheter tip 1000 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 1000.

[0095] As shown, the catheter tip 1000 may be a pressure relief valve 1002. In some cases, the pressure relief valve 1002 may be forced toward the distal end of the catheter tip 1000 and unclog (unlock) an opening 1006 in the catheter tip 1000 in response to pressure from a pump that forces a therapeutic agent through a catheter to which the catheter tip 1000 is coupled. The pressure from the pump may force the pressure relief valve 1002 against a biasing mechanism 1004 (such as a spring or elastomer) to allow the therapeutic agent to leave the biasing mechanism 1004 and release in the absence of pressure to close the opening 1006. The actuation or opening / closing of the pressure relief valve 1002 may help mitigate any foreign body reaction, inflammation, or cell ingress deposits and maintain the opening substantially unobstructed for drug delivery through the catheter.

[0096] Fig.11A 2 is an example catheter tip 1100 in a first configuration according to various aspects of the present disclosure. The catheter tip 1100 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 1100.

[0097] As shown, the catheter tip 1100 can be a pressure-expanded elastomeric tip 1102. In some cases, the elastomeric tip 1102 can be forced toward the distal end of the catheter tip 1100 and open an opening 1006 in the catheter tip 1100 in response to pressure from a pump, which forces the therapeutic agent through the catheter to which the catheter tip 1000 is connected. The pressure from the pump can force the opening 1104 (e.g., Fig. 11B11A) to allow the therapeutic agent to exit the opening 1104, and release in the absence of pressure (as shown in 11A) to close the opening 1104. The opening 1104 in the pressure-expanded elastomeric end 1102 can be formed by stretching a sheet or patch of elastomer or porous ePTFE-elastomer (e.g., silicone or polyurethane) composite and piercing the opening in the material while stretching. In the absence of stretching, the sheet or patch of material and the opening contract and are substantially closed.

[0098] In some cases, during use, the pierced opening allows the therapeutic agent to exit the opening 1104 by bending the pressure-expanded elastomeric tip 1102 outward. When the pressure of the pump or injection mechanism that flexes the pressure-expanded elastomeric tip 1102 drops, the pressure-expanded elastomeric tip 1102 will return to its original compressed state and the pierced opening 1104 will close until the next expansion. The actuation or opening / closing of the pressure-expanded elastomeric tip 1102 can help release (mitigate) any foreign body reaction, inflammation, or cell entry deposits and maintain the opening substantially unobstructed for drug delivery through the catheter.

[0099] Fig.12 2 is another example catheter tip 1200 according to various aspects of the present disclosure. The catheter tip 1200 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 1200.

[0100] As shown, the catheter end 1200 can be a valve structure. In some cases, the valve 1202 disposed in the catheter end 1200 can be opened in response to the pressure from the pump, and the pressure forces the therapeutic agent to pass through the catheter connected to the catheter end 1200. The pressure from the pump can open the valve 1202 so that the therapeutic agent can be released through the distal opening 1204, and the valve 1202 is closed in response to the pressure release or the absence of pressure. The actuation or opening / closing of the catheter end 1200 can help alleviate any foreign body reaction, inflammation or cell entry into the deposit, and maintain the opening substantially unimpeded for delivery of drugs by the catheter. The valve 1202 is confined in the catheter end 1200 and protected from the mechanical influence of the surrounding tissue, which may hinder the valve actuation in other cases. In some cases, the catheter end 1200 may include a plurality of valves 1202, each valve 1202 being configured to open at the same or different prescribed pressures.

[0101] Fig.13 2 is another example catheter tip 1300 according to various aspects of the present disclosure. The catheter tip 1300 can be disposed at the distal end of the elongated body of any catheter discussed herein. As discussed in detail above, the cover 222 can at least partially cover the catheter tip 1300.

[0102] As shown, the catheter end 1300 can be a valve structure. In some cases, the valve 1302 disposed in the catheter end 1300 can be opened in response to the pressure from the pump, and the pressure forces the therapeutic agent to pass through the catheter connected to the catheter end 1300. The pressure from the pump can open the valve 1302 so that the therapeutic agent can be released through at least one opening 1304 (the side opening and / or the distal opening in the catheter end 1300), and the valve 1302 is closed in response to the pressure release or the situation of no pressure. In some cases, the catheter end 1300 may include a side opening 1304 and a distal opening 1304. The actuation or opening / closing of the catheter end 1300 can help alleviate any foreign body reaction, inflammation or cell entry deposits, and maintain the opening substantially unimpeded for delivery of drugs by the catheter. The valve 1302 is confined in the catheter end 1300 and protected from the mechanical influences of the surrounding tissues, which may hinder the valve actuation in other cases. In some cases, catheter tip 1300 may include multiple valves 1302, with each valve 1302 configured to open at the same or different specified pressures.

[0103] The invention of the present application has been described above generally and with reference to specific embodiments. It will be apparent to those skilled in the art that various modifications and changes may be made to the embodiments without departing from the scope of the present disclosure. Therefore, the embodiments are intended to cover modifications and changes of the present invention as long as they fall within the scope of the appended claims and their equivalents.

Claims

1. A device configured to be implanted in a patient, the device comprising: a catheter having an elongated body including a proximal section and a distal section, an internal flow lumen, and at least one opening connected to the internal flow lumen for delivering a therapeutic agent, the distal section being configured to be implanted in a patient, wherein the at least one opening is positioned within the distal section of the elongated body; and A covering is disposed around at least a portion of the distal segment, at least a portion of the distal segment includes the at least one opening, the covering having a porous microstructure configured to selectively enable cell ingrowth and inhibit fibrotic cell infiltration, and wherein the covering is configured to maintain the opening substantially unobstructed for drug delivery through the catheter.

2. The device according to claim 1, characterized in that The cover is an ePTFE membrane.

3. The device according to any one of claims 1 to 2, characterized in that The cover extends from between 1 mm and 100 mm from the distal end of the catheter along the distal section.

4. The device according to any one of claims 1 to 2, characterized in that The catheter is configured for delivering a drug to the intraperitoneal space through the internal flow lumen, and the cover includes a drug dispensing material.

5. The device according to claim 4, characterized in that The catheter is an indwelling catheter configured to be implanted in the intraperitoneal space for up to 20 years.

6. The device according to any one of claims 1 to 2, characterized in that The at least one opening is disposed at a distal end of the catheter.

7. The device according to any one of claims 1 to 2, characterized in that The at least one opening includes a plurality of openings spaced around a circumference of the distal section of the catheter to enable uniform distribution of the therapeutic agent.

8. The device according to claim 7, characterized in that The cover is disposed over the plurality of openings.

9. The device according to any one of claims 1 to 2, characterized in that Also included is a sealing tip disposed at the distal end of the catheter.

10. The device according to any one of claims 1 to 2, characterized in that Also included is an inner layer disposed within the catheter along the inner flow lumen, the inner layer configured to reduce foreign body reaction and inflammation.

11. The device according to any one of claims 1 to 2, characterized in that Also included is at least one of a bioactive agent or a bioactive covering disposed on an outer surface of the catheter.

12. The device according to any one of claims 1 to 2, characterized in that Also included is a self-closing tube section disposed at the distal end of the elongated body.

13. The device according to claim 12, characterized in that The self-closing tube segment is configured to open in response to pressure from a pump forcing the therapeutic agent through the elongated body, and to close in response to the absence of the pressure.

14. The device according to any one of claims 1 to 2, characterized in that Also included is a catheter tip segment disposed at the distal end of the elongated body, the catheter tip segment including a valve configured to open in response to pressure from a pump forcing the therapeutic agent through the elongated body and to close in response to the absence of the pressure.

15. The device according to any one of claims 1 to 2, characterized in that Also included is a pressure-expanded elastomeric tip disposed at the distal end of the elongated body, the pressure-expanded elastomeric tip including an opening configured to open in response to pressure from a pump forcing the therapeutic agent through the elongated body and to close in response to the absence of the pressure.

16. The device according to claim 1, characterized in that The openings are substantially unobstructed to allow for continuous outflow of the therapeutic agent through the at least one opening to deliver the drug to a patient.

17. The device according to claim 16, characterized in that The catheter is configured to deliver the therapeutic agent directly into the intraperitoneal space of the patient.

18. The device according to claim 1, characterized in that The cover includes a porous microstructure to allow cell ingrowth and reduce fibrotic encapsulation.

19. The device according to claim 1, characterized in that The cover is disposed around at least a portion of an outer surface of the distal section.

20. The device according to claim 1, characterized in that The porous microstructure is configured to allow neovascular ingrowth of blood vessels.

Images