Microcatheter manifold adapter and related systems and methods

Abstract

An adapter (1000) for modifying an existing delivery system (100) to improve delivery of an injectable therapeutic substance through the delivery system. The delivery system is an existing delivery system that is formed separately, independent of the manufacture of the adapter. The delivery system includes an administration set (110) and a catheter set (120) that are coupled to each other in fluid communication via a manifold (130). The injectable therapeutic substance may be in the form of microspheres or microbeads that may be retained within the voids of the existing manifold of the delivery system. The adapter (1000) reconfigures the interior of the manifold (130) to promote complete flow of the injectable therapeutic substance through the manifold, rather than being retained or trapped within the manifold and prevented from being delivered to the patient.

Description

[Technical Field]

[0001] The present disclosure relates generally to the field of devices, systems, and methods for delivering therapeutic substances into the body of a patient. In particular, the present disclosure relates to medical devices, systems, and methods for adapting existing injectable therapeutic substance delivery devices, systems, and methods to improve the delivery of injectable therapeutic substances. More specifically, the present disclosure relates to medical devices, systems, and methods for adapting existing therapeutic substance delivery devices, systems, and methods to effectively deliver injectable therapeutic substances in the form of microspheres, microbeads, and the like. [Background technology]

[0002] Various devices, systems, and methods exist for delivering an injectable therapeutic substance into a patient's body. The injectable therapeutic substance may be contained in a vial. Any of a variety of administration sets may be used to access the injectable substance from the vial and deliver the injectable substance to a patient. Typically, an administration set includes a flexible tubular element that is fluidly connected to the vial at one end and has a fitting / connector at the other end for coupling to a catheter or microcatheter that accesses the patient's body to deliver the injectable therapeutic substance. The catheter or microcatheter usually includes a manifold at one end configured to couple to the administration set. The other end of the microcatheter is usually configured to be inserted into the patient's body to deliver the injectable therapeutic substance therein. The manifold usually has a fitting / connector configured to couple with a fitting / connector of the administration set. Various challenges exist regarding whether a particular injectable therapeutic substance can pass completely through the manifold and reach the catheter or microcatheter. For example, the characteristics of some injectable therapeutic substances can cause the injectable therapeutic substance to become clogged within the manifold. Such problems are exacerbated when low doses of injectable therapeutic agent are administered and no more than about 5% of the injectable therapeutic agent is delivered through the manifold into the patient's body. Solutions to these and other problems are desirable. Summary of the Invention

[0003] This Summary is provided to introduce a selection of concepts in a simplified form that are described in more detail below in the Detailed Description. This Summary is not intended to necessarily identify key features or essential features of the claimed subject matter, nor is it intended as an aid in determining the scope of the claimed subject matter. Those skilled in the art will appreciate that each of the various aspects and features of the present disclosure, whether or not described in this Summary, can be used advantageously separately in some cases, or in other cases in combination with other aspects and features of the present disclosure. No limitation on the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, etc. in this Summary.

[0004] In accordance with various principles of the present disclosure, an adapter is configured to modify a separately manufactured delivery system through which an injectable therapeutic substance is delivered into a patient's body. In some aspects, the adapter has an adapter body extending from a proximal end to a distal end, with a lumen defined therethrough extending between the proximal and distal ends of the adapter body. In some aspects, the adapter is sized, shaped, configured, and / or dimensioned to fit within a lumen defined through a manifold of the delivery system, reducing the size of the lumen of the manifold and facilitating flow of the injectable therapeutic substance through the manifold from the proximal end of the manifold to the distal end of the manifold. In some aspects, the proximal end of the adapter is configured to mate with a male fitting of an administration set configured to deliver the injectable therapeutic substance through the manifold, and the distal end of the adapter is configured to be positioned within the lumen of the manifold upstream of the proximal end of a catheter that is within the lumen of the manifold.

[0005] In some embodiments, the lumen of the adapter includes a tapered segment. In some embodiments, the tapered segment is adjacent to the proximal end of the adapter body. In some embodiments, the lumen of the adapter has a constant diameter segment extending from the tapered segment to the distal end of the adapter body. In some embodiments, the tubing element extends within the constant diameter segment of the adapter lumen. In some embodiments, the adapter body is formed from a flexible material and the tubing element is formed from a material that is stiffer than the material of the adapter body. In some embodiments, the adapter body is molded over the stiff tubing element.

[0006] In some embodiments, the proximal end of the adapter is configured to mate against a surface of a fitting on an administration set upstream of the manifold of the delivery system or to receive a male fitting on the administration set within the proximal end of the adapter.

[0007] In some embodiments, the proximal end of the adapter is configured to mate against a face of a fitting of a lineset upstream of a manifold of a delivery system or to receive a male fitting of a lineset within the proximal end of the adapter.

[0008] In accordance with various principles of the present disclosure, an adapter is configured to modify a manifold through which an injectable therapeutic substance flows for delivery into a patient's body. In some aspects, the adapter has an adapter body extending from a proximal end to a distal end, with a lumen defined therethrough extending between the proximal and distal ends of the adapter body. In some aspects, the adapter is sized, shaped, configured, and / or dimensioned for insertion into the lumen defined through the manifold to reduce the size of the lumen of the manifold and facilitate flow of the injectable therapeutic substance through the manifold from the proximal end of the manifold to the distal end of the manifold. In some aspects, the adapter is formed at least in part from a flexible material to fit within the lumen of the manifold and fill the space within the lumen of the manifold. In some aspects, the adapter is sized, shaped, configured, and / or dimensioned and formed from a material to maintain patency of the lumen of the adapter when the adapter body is disposed within the manifold.

[0009] In some embodiments, the lumen of the adapter includes a tapered segment. In some embodiments, the tapered segment is adjacent to the proximal end of the adapter body. In some embodiments, the lumen of the adapter has a constant diameter segment extending from the tapered segment to the distal end of the adapter body. In some embodiments, the tubing element extends within the constant diameter segment of the adapter lumen. In some embodiments, the adapter body is formed from a flexible material and the tubing element is formed from a material that is stiffer than the material of the adapter body. In some embodiments, the adapter body is molded over the stiff tubing element.

[0010] In some embodiments, the tubing element extends within the lumen of the adapter body. In some embodiments, the adapter body is formed from a flexible material and the tubing element is formed from a material that is more rigid than the material of the adapter body. In some embodiments, the adapter body is molded over the rigid tubing element.

[0011] In some embodiments, the lumen of the adapter has a constant diameter segment. In some embodiments, the tubing element extends through the constant diameter segment of the lumen of the adapter. In some embodiments, the adapter body is formed from a flexible material and the tubing element is formed from a material that is stiffer than the material of the adapter body. In some embodiments, the adapter body is molded over the stiff tubing element.

[0012] In some embodiments, the proximal end of the adapter is configured to receive a male fitting of the line set within the proximal end of the adapter to mate against a face of the fitting of the line set upstream of the manifold of the delivery system.

[0013] In accordance with various principles of the present disclosure, a method of reconfiguring a system for delivering an injectable therapeutic substance includes inserting a flexible adapter into a lumen of an existing manifold formed separately and independently from the adapter, and receiving the adapter within the lumen of the manifold so as to occupy space within the lumen of the manifold and reduce the volume within the lumen of the manifold to facilitate flow of the injectable therapeutic substance through the manifold and into the body of a patient.

[0014] In some aspects, the method further includes providing a tubing element within the lumen of the adapter to maintain patency of the lumen of the adapter and facilitate flow of the injectable therapeutic substance through the lumen of the adapter.

[0015] In some aspects, the method further includes mating a male fitting of the line set to the proximal end of the adapter. In some aspects, the method further includes inserting the male fitting of the line set into a lumen of the adapter in the manifold. In some aspects, the method further includes pushing the adapter into the manifold using the male fitting of the line set.

[0016] These and other features and advantages of the present disclosure will become readily apparent from the following detailed description, and the scope of the claimed invention is set forth in the appended claims. While the following disclosure is presented in terms of aspects or embodiments, it should be understood that each aspect may be claimed separately or in combination with aspects and features of that embodiment or any other embodiment. [Brief explanation of the drawings]

[0017] Non-limiting embodiments of the present disclosure are described by way of example with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. The accompanying drawings are provided for illustrative purposes only, and the dimensions, positions, order, and relative sizes reflected in the figures within the drawings may vary. For example, devices may be enlarged so that details can be discerned, but are intended to be reduced in size to fit within, for example, the working channel of a delivery catheter or endoscope. In the figures, identical, nearly identical, or similar elements are typically represented by the same reference character, and redundant description is omitted. For clarity and conciseness, not every element is labeled in every drawing, and not every element of each embodiment is shown unless illustration is necessary to enable those skilled in the art to understand the disclosure.

[0018] The detailed description will be better understood in conjunction with the accompanying drawings, in which like reference numerals represent like elements, as follows: [Figure 1] FIG. 1 is a perspective view of a delivery system including an example embodiment of an adapter formed in accordance with aspects of the present disclosure. [Figure 2] FIG. 2 is an exploded perspective view of the delivery system and adapter as illustrated in FIG. 1. [Figure 3A] 1 is a perspective view of an example embodiment of an adapter formed in accordance with various principles of the present disclosure; [Figure 3B] FIG. 3B is a cross-sectional view taken along line IIIB-IIIB in FIG. 3A. [Figure 4A] 1 is a perspective view of an example embodiment of an adapter formed in accordance with various principles of the present disclosure; [Figure 4B] FIG. 4B is a cross-sectional view taken along line IVB-IVB in FIG. 4A. [Figure 5A] 1 is a perspective view of an example embodiment of an adapter formed in accordance with various principles of the present disclosure; [Figure 5B] FIG. 5B is a cross-sectional view taken along line VB-VB in FIG. 5A. DETAILED DESCRIPTION OF THE INVENTION

[0019] The following detailed description should be read with reference to the drawings illustrating exemplary embodiments. It should be understood that the present disclosure is not limited to the particular embodiments described, as such may vary. All devices, systems, and methods described herein are examples of devices and / or systems and / or methods implemented in accordance with one or more principles of the present disclosure. Each example embodiment is provided for illustrative purposes and is merely an example, not the only way, to implement these principles. Thus, references to elements or structures or features in the drawings should be recognized as references to example embodiments of the present disclosure and should not be understood as limiting the disclosure to the particular elements, structures, or features shown. Other examples of ways to implement the disclosed principles will occur to those skilled in the art upon reading and understanding this disclosure. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made in the present disclosure without departing from the scope or spirit of the present subject matter. For example, features illustrated or described as part of one embodiment can be used with another embodiment to yield a still further embodiment. Accordingly, the present subject matter is intended to cover all such modifications and variations that come within the scope of the appended claims and their equivalents.

[0020] It will be understood that the present disclosure is described in this application at various levels of detail. In certain instances, details that are not necessary for those skilled in the art to understand the present disclosure or that would make it difficult for those skilled in the art to appreciate other details may be omitted. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting beyond the scope of the appended claims. Unless otherwise defined, technical terms used herein should be understood as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. All of the devices and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure.

[0021] As used herein, "proximal" refers to a direction or location closest to a user (e.g., a medical professional or clinician or technician or operator or physician, such terms are used interchangeably herein without limitation, and include automated controller systems, etc.), such as when using the device (e.g., when introducing the device into a patient or during implantation, placement, or delivery) and / or closest to a delivery device, and "distal" refers to a direction or location furthest from a user (e.g., when using the device (e.g., when introducing the device into a patient or during implantation, placement, or delivery) and / or closest to a delivery device). "Longitudinal" means extending along the length or major dimension of an element. A "longitudinal axis" extends along the length of an element, but is not necessarily straight, and does not necessarily maintain a fixed shape when the element is bent or curved. Also, "axial" generally refers to a direction along the longitudinal axis. However, it will be understood that references to axial or longitudinal movement with respect to the above-described systems or elements thereof need not be strictly limited to axial and / or longitudinal movement along the longitudinal or central axis of the referenced elements. "Center" means at least approximately bisecting the center point and / or being approximately equidistant from the periphery or boundary, and "central axis," with respect to an opening, means a line at least approximately bisecting the center point of the opening and extending longitudinally along the length of the opening when the opening comprises, for example, a tubular element, channel, cavity, or bore. As used herein, "lumen" or "channel" or "hole" or "passage" is not limited to a circular cross-section. As used herein, the "free end" of an element refers to the terminus of the element from which it does not extend. Terms such as "at the end," "on the end," "adjacent to the end," "along the end," and the like may be used interchangeably herein without limitation, unless otherwise specified, and are understood to indicate general relative spatial relationships, rather than precisely defined locations. Finally, reference to "at" a location or area is intended to include the vicinity (e.g., along, adjacent, etc.) and / or vicinity of that location or area.

[0022] The present disclosure describes devices, systems, and methods for delivering injectable treatment materials into a patient's body. It will be understood that, as used herein, the terms "injectable treatment material" or "injectables" are used for convenience and are not intended to be limiting, and refer to injectable forms of treatment materials, including pharmaceuticals, diagnostic agents (including, but not limited to, imaging agents), treatment devices (including, but not limited to, particles, beads, spheres, etc.), and the like, including solid particles carried by a fluid medium and / or fluid returned by a fluid medium. Injectable materials can be liquids, solids (e.g., dry solids such as microspheres that are typically suspended / carried in a fluid), or combinations thereof (e.g., microspheres in deionized water, microspheres with fluoroscopic contrast agents, etc.). Injectable materials can be used for, but are not limited to, diagnosis, imaging, treatment, therapy, etc., although the present disclosure is not limited in this respect. Furthermore, the injectable substance may be in any of a variety of desired or indicated forms, such as a fluid (e.g., a typical pharmaceutical form), a gel, or a solid (e.g., solid particles such as beads, microbeads, microspheres, or other particles known for therapeutic applications, typically suspended / carried in a fluid). In some cases, the injectable therapeutic substance may be beads or microbeads or microspheres (such terms may be used interchangeably herein, and for convenience and without limitation, will be referred to generally as microspheres) typically suspended in a fluid medium.

[0023] The delivery devices, systems, and methods include administration sets (which may also be referred to, without limitation, as line sets or tubing sets) that connect a container containing an injectable therapeutic substance to a catheter configured to deliver the injectable therapeutic substance into a patient's body. The container of the injectable therapeutic substance may be a vial, a syringe, or the like, and the disclosure is not limited in this regard. Typically, the catheter includes a manifold having a connector, and the administration set includes a connector that can be connected to the connector of the manifold. Furthermore, microcatheters (e.g., having an inner diameter of about 0.40 to 1.30 mm) are typically used to deliver microspheres into a patient's body. However, references to "microcatheter" herein need not be so limited and should be understood to include catheters, neurocatheters, and the like, and the disclosure is not limited by the size, dimensions, etc. of the catheter.

[0024] In some examples, the injectable therapeutic substance may be a radioactive medical injectable therapeutic substance (e.g., a radiopharmaceutical, a radiotherapeutic agent, a radiodiagnostic agent, a radioimaging agent, a tracer, etc.), although the present disclosure is not limited in this respect. For example, the injectable therapeutic substance delivered using the devices, systems, and methods of the present disclosure may be beads, microbeads, or microspheres (e.g., irradiated beads, microbeads, or microspheres). An example of a radioactive medical injectable therapeutic substance is TheraSphere™ Y-90 Glass Microspheres (glass microspheres infused with yttrium, specifically Y-90), sold by Boston Scientific Corporation for cancer treatment (radiotherapy). TheraSphere™ microspheres can be delivered to tumors within a patient's body via a microcatheter and concentrated in tumor microvasculature for precise, localized tumor ablation. Additionally or alternatively, another radioactive medical injectable substance may be provided for imaging and diagnostic purposes. More specifically, microspheres, which may be formed of a suitable material such as glass, may be infused with, or labeled with, a radioactive substance such as technetium (particularly Tc-99m). The Tc-99m-labeled microspheres have substantially the same diameter (average diameter of about 25 μm) and substantially the same flow characteristics as TheraSphere™ microspheres, and thus may serve as a substitute or surrogate for TheraSphere™ microspheres. Thus, the Tc-99m microspheres can be used for imaging and diagnosis prior to injection of TheraSphere™ microspheres, which have a significantly longer half-life (Y-90 has a half-life of 64 hours, compared to Tc-99m's 6-hour half-life).It will be appreciated that the surface textures on device and system components formed in accordance with various principles of the present disclosure preferably have structures smaller than the diameter of passing particles to ensure that those particles do not "stick" to the device and system components.

[0025] Microspheres, such as TheraSphere™ microspheres, emit high-intensity beta radiation at low doses. They emit high-intensity beta radiation at doses as low as 1 GBQ per 15 ml of carrier, such as water, or even lower doses, such as 0.5 GBQ per 15 ml of carrier, when delivered via syringe with 20 cc of saline solution into a vial filled with up to 0.6 ml of pyrogen-free water. When microspheres are injected into a microcatheter at low doses and low flow rates, it is important for the patient to receive the full dose. However, various aspects of current delivery systems and their components can prevent full-dose delivery. For example, microspheres may clump within the system, for example, along the hub and components that connect the system. For example, vials containing injectable therapeutic substances are typically fluidly connected to an administration set, which is typically connected to a microcatheter via a manifold for administration into the patient's body. In this case, there may be an air gap between the administration set connector and the inner lumen of the microcatheter. More specifically, voids may exist within the manifold fluidly connected between the administration set and the microcatheter. As microspheres pass through the microcatheter manifold, they may adhere to the sidewalls of the manifold, preventing the full dose of microspheres from reaching the disease site. Repeated tapping to release the microspheres may unnecessarily expose the medical personnel to radiation during tapping due to the proximity and lack of shielding between the active microspheres and the medical personnel. Furthermore, such tapping processes are generally uncontrolled and variable, which not only burdens the medical personnel but can also produce inconsistent results, potentially affecting delivery efficiency and the microcatheter's internal residence time.

[0026] Furthermore, up to 10 flushing cycles may be performed to deliver the microspheres to the diseased site. In the case of glioma, fewer flushes are desirable. Reducing the number of flushes required to remove microspheres from the vial and delivery system (including the administration set, manifold, and microcatheter) reduces patient risk in several ways. First, reducing the number of flushes reduces the risk of injecting excessive fluid at an excessive rate, which can increase the risk of backflow near the catheter tip. Backflow of microspheres can result in delivery of therapeutic substances to non-affected areas, a potential patient risk. Furthermore, injecting excessive fluid at an excessive rate can lead to tissue volume limitations or edema. Second, reducing the number of flushes shortens the procedure time and reduces the catheter's internal residence time, reducing potential patient risk. Finally, reducing the number of flushes improves the user experience of the system by reducing the required internal strain, reducing the psychological burden on the user, and / or shortening the overall procedure time.

[0027] In accordance with various principles of the present disclosure, a separately formed adapter is separate from an existing, preformed, separately formed delivery system and configured to mate with the delivery system to facilitate the complete flow of an injectable therapeutic substance through the delivery system to a patient. As used herein, descriptors such as "existing," "preformed," "separately formed," "separately manufactured," and the like are intended to refer to an already-fabricated device or system, such as a commercially available, off-the-shelf device or system, formed without consideration of a particular injectable therapeutic substance, such as the microspheres described herein. An adapter, as described herein, is formed separately and independently in accordance with various principles of the present disclosure to modify various characteristics of an already-fabricated device or system. In this instance, a "preformed" delivery system is one that is formed separately and independently from the adapter and not necessarily for the purpose for which the adapter is formed. The adapter has a lumen that is in fluid communication with the delivery lumen of the administration set and the lumen of the microcatheter of the delivery system, through which the injectable therapeutic substance is delivered into the patient's body. In some embodiments, the adapter is configured to be disposed within a manifold coupled between the administration set and the catheter. The manifold is configured to mate with the administration set and / or catheter to seal the connection therebetween and ensure full flow of the injectable therapeutic substance through the manifold. In some embodiments, the adapter mates with a male fitting on the administration set to seal the administration set fitting. In some embodiments, the adapter has a tapered inner diameter that directs the injectable therapeutic substance into the microcatheter. The adapter's exterior shape can be configured to prevent the injectable therapeutic substance from filling the internal void space of the manifold. The adapter can be configured to function in vertical and horizontal positions, ensuring that beads are delivered to the disease site regardless of how the healthcare professional positions the delivery system during use.In some embodiments, a tubular insert (eg, a tubular metal insert) is provided within at least a portion of the manifold to provide column strength to the distal end of the adapter's lumen.

[0028] It will be appreciated that an adapter formed in accordance with various principles of the present disclosure minimizes the flushing that may be required, thereby reducing the catheter's in-body residence time, shortening overall procedure time, and reducing the risk of unstable microsphere delivery, microsphere reflux, tissue volume limitations, edema, etc.

[0029] It will further be appreciated that adapters formed in accordance with various principles of the present disclosure eliminate the need to tap components of a delivery system to ensure that injectable therapeutic substances (e.g., beads) do not become lodged within one or more components of the delivery system. For example, placing an adapter formed in accordance with various principles of the present disclosure within an existing delivery system manifold facilitates the flow of injectable therapeutic substances, such that a medical professional administering the injectable therapeutic substance does not need to tap the manifold (e.g., with a separate instrument) as the dose is delivered to the diseased site. Thus, the use of an adapter formed in accordance with various principles of the present disclosure reduces the risk of increased radiation exposure to both the medical professional and the patient, reduces catheter dwell time within the body, shortens overall procedure time, and reduces the risk of delivery of unstable microspheres. Adapters formed in accordance with various principles of the present disclosure are applicable to any manifold, as the adapter is formed to fit the specifications of the existing manifold and meets the characteristics of the injectable therapeutic substance flowing through the manifold. Furthermore, adapters formed in accordance with various principles of the present disclosure are applicable to any microcatheter, catheter, etc. Even though the outer shape of the adapter depends on the catheter (when inserted into the same manifold lumen as the catheter), the inner diameter and shape of the adapter ensure proper and complete delivery of the injectable therapeutic substance.

[0030] Various embodiments of adapters for devices and systems for delivering injectable therapeutic substances and related methods are described below with reference to examples illustrated in the accompanying drawings. References herein to "one embodiment," "an embodiment," "some embodiments," "other embodiments," etc. indicate that one or more particular features, structures, concepts, and / or characteristics in accordance with the principles of the present disclosure may be included in connection with the embodiment. However, such references do not necessarily imply that all embodiments include the particular feature, structure, concept, and / or characteristic, or that an embodiment includes all features, structures, concepts, and / or characteristics. Some embodiments may include one or more such features, structures, concepts, and / or characteristics in various combinations thereof. It should be understood that one or more of the features, structures, concepts, and / or characteristics described with reference to one embodiment can be combined with one or more of the features, structures, concepts, and / or characteristics of any of the other embodiments provided herein. That is, any of the features, structures, concepts, and / or properties described herein can be mixed and matched to form hybrid embodiments, and such hybrid embodiments are within the scope of the present disclosure. Moreover, references to "one embodiment," "an embodiment," "some embodiments," "other embodiments," etc. in various places herein do not necessarily all refer to the same embodiment, and separate or alternative embodiments are not necessarily mutually exclusive of other embodiments. Furthermore, it is understood that the various features, structures, concepts, and / or properties of the disclosed embodiments are independent and distinct from one another and can be used or presented individually or in various combinations with one another to create alternative embodiments that are considered part of the present disclosure. Accordingly, the present disclosure is not limited to only the embodiments specifically described herein, and the example embodiments disclosed herein are not intended to limit the broader aspects of the present disclosure, as it would be prohibitively tedious to describe all of the many possible combinations and subcombinations of features, structures, concepts, and / or properties.It should be understood that the various dimensions provided herein are examples, and that one of ordinary skill in the art can readily determine appropriate ranges of standard deviation and acceptable variation therefrom that are encompassed by the present disclosure and any claims related thereto. The following description is merely illustrative of embodiments and is not intended as limiting the broader aspects of the present disclosure.

[0031] It will be understood that common features will be identified by common reference elements, and that for brevity and convenience, and without intending to be limiting, descriptions of common features will generally not be repeated. For clarity, not all components having the same reference number will be numbered. Furthermore, groups of similar elements may be indicated by a number and a letter, and one or more of such elements or groups of such elements may be generally referred to by the number alone (without including the letter associated with each similar element). In the following description, it will be understood that similar elements or components among the various illustrated embodiments of adapters formed in accordance with various principles of the present disclosure will generally be designated by the same reference number in multiples of 100, and redundant descriptions will generally be omitted for brevity. Furthermore, certain features in one embodiment may be used across different embodiments and will not necessarily be individually labeled when appearing in different embodiments.

[0032] An injectable therapeutic substance delivery system 100 formed in accordance with various principles of the present disclosure is shown in Figures 1 and 2 and includes an administration set 110 at a proximal end 101 and a microcatheter set 120 at a distal end 103. The proximal end of the administration set 110 is coupled to a vial containing an injectable therapeutic substance. The proximal end of the administration set 110, the vial, and the injectable therapeutic substance may be of any configuration known to those skilled in the art, depending, for example, on the type of injectable therapeutic substance to be delivered by the injectable therapeutic substance delivery system 100, and therefore illustrations thereof are not necessary for a complete understanding of these elements by one of ordinary skill in the art.

[0033] The administration set 110 and microcatheter set 120 of the illustrated example embodiment are coupled to the manifold 130 of the example embodiment. More specifically, the distal end 113 of the administration set 110 is coupled to the proximal end 131 of the manifold 130, and the proximal end 121 of the microcatheter set 120 is coupled to the distal end 133 of the manifold 130. With such a configuration, the lumen 115 defined in and through the tubing element 112 of the administration set 110 is in fluid communication with the lumen 125 defined in and through the microcatheter 122 of the microcatheter set 120 via the lumen 135 defined in and through the manifold 130. The distal end of the microcatheter 122 may be configured for insertion into a patient in a manner known to those skilled in the art for delivery of an injectable therapeutic substance into the patient's body. Therefore, illustration of the distal end of the microcatheter 122 is not considered necessary for one of ordinary skill in the art to fully understand such elements.

[0034] As shown in more detail in FIG. 2 , the administration set 110 includes a fitting 114 extending distally from a distal end 113 of the administration set 110. It will be understood that terms such as fitting, connector, coupling, coupler, adapter, and the like may be used interchangeably herein without limitation, unless otherwise specified. The administration set fitting 114 is configured to couple with a corresponding fitting 132 extending proximally from a proximal end 131 of a manifold 130. In the illustrated example of one embodiment, the female portion 114a of the administration set fitting 114 is configured to fit over the manifold fitting 132, and the male portion 114b of the administration set fitting 114 is configured to fit within the manifold fitting 132 to fluidly connect the administration set lumen 115 to the manifold lumen 135. Optionally, the administration set female portion 114a and the manifold fitting 132 have interengaging configurations to hold the elements in place relative to one another. In the example embodiment shown in Figures 1 and 2, the administration set female portion 114a and the manifold fitting 132 have respective interengaging threads 117, 137. However, the present disclosure is not limited in this respect and encompasses other interengaging configurations known to those skilled in the art.

[0035] 1 and 2 , the microcatheters 122 of the microcatheter set 120 may be coupled to the manifold 130 via a strain relief 124 extending along a proximal portion of the microcatheter 122. The strain relief 124 may extend onto a distal fitting 134 of the manifold 130 that extends distally from a distal end 133 of the manifold 130. The microcatheters 122 may extend further proximally from the strain relief 124 into a lumen 135 of the manifold to more closely communicate with the lumen 115 defined in the administration set 110.

[0036] Optionally, the manifold 130 includes one or more extensions 138, such as wings, extending radially outward from the outer surface of the manifold 130 to facilitate gripping thereof. The extensions 138 may extend radially outward from and longitudinally along the manifold 130 sufficiently to facilitate manipulation of the manifold 130, such as rotation of the manifold 130 relative to at least the administration set 110, to couple the manifold 130 and administration set 110 together.

[0037] The present disclosure relates to devices, systems, and methods for modifying existing, preformed, separately formed, separately manufactured, etc., injectable therapeutic substance delivery systems, such as those described above, after the injectable therapeutic substance delivery system is manufactured. More specifically, the devices, systems, and methods of the present disclosure improve fluid flow through existing separately formed injectable therapeutic substance delivery systems, such as those described above. Thus, the manufacture of adapter devices and systems formed in accordance with various principles of the present disclosure need not be constrained by the manufacturing requirements of the injectable therapeutic substance delivery system in which they are used. Thus, adapter devices and systems formed in accordance with various principles of the present disclosure improve fluid flow within the manifold of an existing injectable therapeutic substance delivery system, providing increased options for accommodating the requirements of specific injectable therapeutic substances. Thus, the size, shape, configuration, and / or dimensions of devices and / or systems formed in accordance with various principles of the present disclosure can be selected to fit the requirements of the injectable therapeutic substance delivery system and the injectable therapeutic substance to be delivered therethrough. For example, the size, shape, configuration, and / or dimensions of devices and / or systems formed according to various principles of the present disclosure may be selected taking into consideration the properties, characteristics, features, etc. of the injectable therapeutic substance delivered by the injectable therapeutic substance delivery system in which the devices and / or systems of the present disclosure are used. For example, the materials of components of devices and systems formed according to various principles of the present disclosure may be specifically selected to withstand the radiation exposure of the radioactive injectable therapeutic substance passing therethrough.

[0038] In accordance with various principles of the present disclosure, a separately formed adapter 1000 is configured to be inserted into the lumen 135 of the manifold 130 of the injectable therapeutic substance delivery system 100, as described above. The adapter 1000 has an adapter body extending from a proximal end 1001 to a distal end 1003, the adapter body configured to fit within the manifold lumen 135 and adapt the existing or pre-formed manifold 130 for delivery of an injectable therapeutic substance that requires modified flow characteristics from those resulting from flow through at least the formed manifold 130. For example, the adapter 1000 formed in accordance with various principles of the present disclosure reduces the size of the manifold lumen 135, facilitating the flow of microbeads or other injectable therapeutic substance, as described above, to improve delivery of the injectable therapeutic substance to the patient by aiding in the reduction of the diameter of the flow path from the administration set 110 to the microcatheter set 120.

[0039] An example embodiment of an adapter 1000 formed in accordance with various principles of the present disclosure is shown in FIGS. 1 and 2 as extending into a manifold lumen 135. The proximal end 1001 of the illustrated example of the adapter 1000 is configured to receive the male portion 114b of the administration set fitting 114. For example, a distal portion of the male portion 114b of the administration set fitting 114 may extend into the adapter's lumen 1005. The distal end 1003 of the adapter 1000 is inserted further into the manifold lumen 135, and the body of the adapter 1000 occupies space within the manifold lumen 135, thereby reducing the size of the manifold lumen 135 and thereby facilitating the flow of an injectable therapeutic substance, such as microspheres, through the manifold's lumen 135. It has been found that reducing the volume within the manifold lumen 135 reduces the amount of injectable therapeutic substance, preventing microspheres from becoming trapped or otherwise lodging within the voids of the manifold lumen 135. The proximal end 121 of the microcatheter 122 is inserted into the distal end 133 of the manifold 130 adjacent the distal end 1003 of the adapter 1000. Optionally, a step or shoulder is provided within the manifold 130 to position the proximal end 121 of the microcatheter 122. The distal end 1003 of the adapter 1000 may be located upstream of the proximal end 121 of the microcatheter 122, or may optionally abut the proximal end 121 of the microcatheter 122. It will be understood that other configurations, as may depend on one or more characteristics of the injectable therapeutic substance delivery system 100 and / or the injectable therapeutic substance, are within the scope and spirit of the present disclosure.

[0040] Because the adapter 1000 formed in accordance with various principles of the present disclosure is formed separately from the injectable therapeutic substance delivery system 100, its material need not be limited by the manufacturing process used in connection with the injectable therapeutic substance delivery system 100. Preferably, however, the material of the adapter 1000 is selected with at least compatibility with the injectable therapeutic substance delivery system 100 in mind. The material of the adapter 1000 formed in accordance with various principles of the present disclosure is a moldable material, such as a moldable resin. Additionally or alternatively, the material of the adapter 1000 formed in accordance with various principles of the present disclosure is pliable to conform to and / or form a seal with the components with which it is used, yet has sufficient column strength to not collapse under compression in a manner that would undesirably affect material flow. As can be appreciated, the size, shape, configuration, and / or dimensions of the wall of the body of the adapter 1000 are selected and the material is sufficiently strong and crush-resistant so that the patency of the adapter's lumen 1005 is maintained and the flow of an injectable therapeutic substance, such as microspheres, is not compromised or impeded. For example, the length of the adapter 1000 can be determined based on the length of the manifold's lumen 135 to ensure that the adapter 1000 has sufficient space within the manifold's lumen 135 so that compression does not occur within the manifold's lumen 135 (which could impede flow through the adapter 1000).Examples of materials that may be used include, but are not limited to, thermoplastic elastomers such as polyether block amides (e.g., Pebax® 25d or 35d block copolymers, manufactured by Arkema, composed of hard polyamide blocks and soft polyether blocks); thermoplastic polyester elastomers (e.g., Hytrel® block copolymers, manufactured by DuPont, composed of hard (crystalline) segments of polybutylene terephthalate and soft (amorphous) segments based on polyether chemistry); thermoplastic polyurethanes (e.g., Pellethane® aromatic polyethers and polyesters, manufactured by Lubrizol); thermoplastic vulcanizates (e.g., Santoprene® dynamically vulcanized polymer alloys, manufactured by Celanese, composed of cured ethylene propylene diene monomer (EPDM) rubber); DEHP-free PVC (di(2-ethylhexyl) phthalate-free polyvinyl chloride), and the like. Various configurations of example embodiment adapters 1100, 1200, 1300 formed in accordance with various principles of the present disclosure are shown in further detail in Figures 3A, 3B, 4A, 4B, 5A, and 5B.

[0041] The lumen of an adapter formed according to various principles of the present disclosure can have two or more geometric configurations. For example, in Figures 3A and 3B, the example embodiment of adapter 1100 shown has lumen 1105 having a proximal tapered segment 1105a and a distal segment 1105b having a different taper than the proximal tapered segment 1105a. For example, distal segment 1105b can have a smaller taper than proximal tapered segment 1105a. As shown in Figures 3A and 3B, distal segment 1105b can have a substantially constant inner diameter (i.e., substantially non-tapered).

[0042] Optionally, a tubing element may be inserted into at least a portion of the lumen of an adapter formed according to various principles of the present disclosure. The tubing element may be configured to assist and / or guide the flow of an injectable therapeutic substance through the adapter and further through the injectable therapeutic substance delivery system 100 into the patient's body. Such a tubing element may be provided within a lumen of an adapter having a constant diameter or a lumen of an adapter having a varying diameter. The tubing element may have a constant diameter or may be tapered, depending on the characteristics of the injectable therapeutic substance, the adapter lumen, the material of the tubing element, etc. For example, a tapered tubing element may be provided within a substantially constant diameter segment of the adapter lumen to add a taper to the lumen. The tubing element may be formed from a material that is more rigid than the material from which the adapter is formed. For example, the rigid tubing element may provide structural support to the flexible adapter (e.g., resist collapse or at least partial collapse of the adapter lumen, making it susceptible to impairing and / or obstructing the flow of injectable therapeutic substance through the collapsed area), such as in a segment of the adapter lumen that has a reduced diameter relative to the diameter of another segment of the adapter lumen. The rigid tubing element may be formed from stainless steel or any other biocompatible metal or other biocompatible material. Optionally, the adapter body material is molded over the tubing element. Optionally, the exterior of the tubing element is configured (e.g., textured, corrugated) to provide mechanical interfit with the overmolded adapter material to reduce, and preferably eliminate, relative movement therebetween.

[0043] 4A and 4B illustrate an example embodiment of an adapter 1200 formed in accordance with various principles of the present disclosure, with at least a portion of the lumen 1205 of the adapter 1200 being provided with a rigid tubing element 1210. The segment in which the rigid tubing element 1210 is provided is the distal segment 1105b and has a substantially constant diameter. However, the rigid tubing element 1210 may alternatively or additionally be disposed within the proximal tapered segment 1205a of the adapter lumen 1205 and / or within a tapered segment of the adapter lumen 1205. Optionally, the rigid tubing element 1210 may be provided with a locking flange 1212 at one or both ends to facilitate attachment of the rigid tubing element 1210 to the adapter 1200 and to prevent the rigid tubing element 1210 from becoming dislodged from the adapter 1200.

[0044] It will be understood that various other modifications may be made to the adapter as described herein without departing from the general principles of the present disclosure. The configuration of the adapter may be altered internally or externally, as determined based on various factors, such as the nature, properties, and characteristics of the injectable therapeutic substance and / or the injectable therapeutic substance delivery system and its components in which the adapter is used (e.g., the size, shape, configuration, and / or dimensions of the manifold, such as the interior of the manifold). Various characteristics of adapters formed in accordance with various principles of the present disclosure may be varied to ensure the desired flow of the injectable therapeutic substance, for example, to reduce turbulence and create high shear forces at the surface to minimize and possibly eliminate spaces where the injectable therapeutic substance (e.g., microspheres) may aggregate. In some cases, the taper and / or length of the lumen of an adapter formed in accordance with various principles of the present disclosure may be varied. In the example embodiment of the adapter 1300 illustrated in Figures 5A and 5B, the proximal segment 1305a of the lumen 1305 defined therethrough has a greater taper and a shorter length than the taper and length of the proximal segment 1105a of the example embodiment of the adapter 1100 illustrated in Figures 3A and 3B. The longer proximal tapered segment 1105a of the adapter 1100 of Figures 3A and 3B may allow the male portion 114b of the administration set fitting 114 to be inserted into the adapter's lumen 1105 and / or may be compressed and sealed when tightening the connection between the administration set 110 and the manifold 130. In contrast, the shorter proximal tapered segment 1305a of the adapter 1300 of Figures 5A and 5B may be configured to mate with the face of the administration set fitting 114. The male portion 114b of the administration set fitting 114 can be used to push adapters 1000, 1100, 1200, 1300 formed according to various principles of the present disclosure into a separately manufactured manifold 130.

[0045] It will be understood that all devices, systems, and methods described herein are examples of devices, systems, and / or methods implemented in accordance with one or more principles of the present disclosure. Various features described with respect to one embodiment may be applied to other embodiments, whether or not explicitly indicated. It will be understood that the examples described herein are not the only ways of implementing these principles, but are merely examples and are not intended as limitations on the broader aspects of the present disclosure. Thus, references to elements or structures or features in the drawings should be recognized as references to example embodiments of the present disclosure and should not be understood as limiting the disclosure to the particular elements, structures, or features shown. Thus, the present invention is not limited to only the embodiments specifically described herein. Other examples of ways of implementing the disclosed principles, and various additional advantages of the various aspects, features, components, and structures of the devices and systems disclosed herein, will be apparent to those skilled in the art upon reading and understanding this disclosure.

[0046] The foregoing description has broad applicability and is presented for purposes of illustration and explanation, and is not intended to limit the disclosure to the form or forms disclosed herein. It will be understood that various additions, modifications, and substitutions may be made to the embodiments disclosed herein without departing from the concept, spirit, and scope of the disclosure. In particular, it will be apparent to those skilled in the art that the principles of the disclosure may be embodied in other forms, structures, arrangements, proportions, and with other elements, materials, and components without departing from the concept, spirit, or scope or characteristics thereof. For example, various features of the disclosure are grouped together in one or more aspects, embodiments, or configurations for the purpose of streamlining the disclosure. However, it should be understood that various features of a particular aspect, embodiment, or configuration of the disclosure may be combined in alternative aspects, embodiments, or configurations. While the disclosure is presented in terms of embodiments, it should be understood that various individual features of the subject matter need not all be present to achieve at least some of the desired properties and / or advantages of the subject matter or such individual features. Those skilled in the art will understand that the present disclosure can be used with many modifications, or modifications of the structure, arrangement, proportions, materials, components, and the like used in implementing the disclosure, that are particularly adapted to particular environments and operating requirements, without departing from the principles or spirit or scope of the disclosure. For example, elements shown as integrally formed may be comprised of multiple pieces, or elements shown as multiple pieces may be integrally formed, operations of elements may be reversed or changed, and sizes or dimensions of elements may be changed. Similarly, although operations or actions or procedures are described in a particular order, this should not be construed as requiring such a specific order to achieve desirable results, or that all operations or actions or procedures should be performed. Additionally, other implementations are within the scope of the following claims. In some cases, the operations recited in the claims can be performed in a different order and still achieve desirable results.The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, and the scope of the claimed subject matter is indicated by the appended claims and is not limited to the foregoing description or to the specific embodiments or configurations described or illustrated herein. In view of the above, individual features of any embodiment may be used and claimed separately or in combination with features of that embodiment or any other embodiment, and the scope of the subject matter is indicated by the appended claims and is not limited to the foregoing description.

[0047] In the foregoing description and in the claims that follow, it will be understood that: As used herein, the terms "at least one," "one or more," and "and / or" are open-ended expressions that are both conjunctive and disjunctive in operation. Terms such as "a," "an," "the," "first," and "second" do not exclude a plurality. For example, the terms "a" or "an" entity, as used herein, refer to one or more of that entity. Thus, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein. As used in this specification and the appended claims, the term "or" is generally used in its sense including "and / or" unless the content clearly dictates otherwise. As used herein, the conjunction "and" includes each of the structures, components, features, etc. so connected, unless the context clearly dictates otherwise, and the conjunction "or" includes one or the other of the structures, components, features, etc. so connected, alone or in any combination and number, unless the context clearly dictates otherwise. All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, rear, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, counterclockwise, etc.) are used for identification purposes only to aid the reader's understanding of this disclosure and / or serve to distinguish regions of associated elements from one another, and do not limit the associated elements, particularly with respect to position, orientation, or use of this disclosure. References to connections (e.g., attached, coupled, connected, engaged, and joined) should be construed broadly and, unless otherwise indicated, can include intermediate members between groups of elements and relative movement between elements. Thus, connective references do not necessarily imply that two elements are directly connected and in a fixed relationship to one another. Distinguishing references (e.g., primary, secondary, first, second, third, fourth, etc.) are not intended to imply importance or priority, but are used to distinguish one feature from another.

[0048] The following claims are incorporated by reference into this detailed description, with each claim standing on its own as a separate embodiment of the present disclosure. In the claims, the terms "comprises," "comprising," "including," and "comprises" do not exclude the presence of other elements, components, features, groups, regions, integers, steps, operations, etc. In addition, although individual features may be included in different claims, they may be advantageously combined, and their inclusion in different claims does not imply that a combination of features is not feasible and / or advantageous. In addition, a reference to the singular does not exclude a plurality. Reference signs in the claims are provided merely as a clarifying example and should not be construed as limiting the scope of the claims in any way.

Claims

1. 1. An adapter configured to modify a separately manufactured delivery system for delivering an injectable therapeutic substance into a patient's body, the adapter comprising an adapter body extending from a proximal end to a distal end; a lumen defined through the adapter body extending between the proximal end and the distal end of the adapter body; the adapter is sized, shaped, configured, and / or dimensioned to fit within a lumen defined through a manifold of the delivery system, reducing the size of the lumen of the manifold and facilitating flow of the injectable therapeutic substance through the manifold from a proximal end of the manifold to a distal end of the manifold; the proximal end of the adapter is configured to mate with a male fitting of an administration set configured to deliver an injectable therapeutic substance through the manifold; The adapter, wherein the distal end of the adapter is configured to be positioned within the lumen of the manifold upstream of a proximal end of a catheter that is within the lumen of the manifold.

2. The adapter of claim 1 , wherein the lumen of the adapter includes a tapered segment.

3. The adapter of claim 2 , wherein the tapered segment is adjacent a proximal end of the adapter body.

4. The adapter of claim 2 or 3, wherein the adapter lumen has a constant diameter segment extending from the tapered segment to the distal end of the adapter body.

5. The adapter of any one of claims 1 to 4, further comprising a tubing element extending within the constant diameter segment of the adapter lumen.

6. The adapter of claim 5 , wherein the adapter body is formed from a flexible material and the tubular element is formed from a material that is stiffer than the material of the adapter body.

7. The adapter of claim 6 , wherein the adapter body is molded over the rigid tubular element.

8. An adapter according to any one of claims 1 to 7, wherein the proximal end of the adapter is configured to fit against a surface of a fitting of an administration set upstream of the manifold of the delivery system or to receive a male fitting of the administration set within the proximal end of the adapter.

9. 1. An adapter configured to modify a manifold through which an injectable therapeutic substance flows for delivery into a patient's body, the adapter comprising an adapter body extending from a proximal end to a distal end; a lumen defined through the adapter body extending between a proximal end and a distal end of the adapter body; the adapter is sized, shaped, configured, and / or dimensioned for insertion into a lumen defined through the manifold to reduce the size of the lumen of the manifold and facilitate flow of the injectable therapeutic substance through the manifold from a proximal end of the manifold to a distal end of the manifold; the adapter is formed at least in part from a flexible material so as to fit within the lumen of the manifold and fill a space within the lumen of the manifold; The adapter is sized, shaped, configured, and / or dimensioned, and formed from materials, such that when positioned within the manifold, the adapter body maintains patency of the adapter lumen.

10. The adapter of claim 9 , wherein the lumen of the adapter includes a tapered segment.

11. The adapter of claim 10 , wherein the tapered segment is adjacent a proximal end of the adapter body.

12. The adapter of claim 10 or 11, wherein the adapter lumen has a constant diameter segment extending from the tapered segment to the distal end of the adapter body.

13. 13. The adapter of any one of claims 9 to 12, further comprising a tubing element extending within the constant diameter segment of the adapter lumen, the adapter body being formed from a flexible material and the tubing element being formed from a material that is more rigid than the material of the adapter body.

14. 1. A method of reconstituting a system for delivering an injectable therapeutic substance, comprising: inserting a flexible adapter into a lumen of an existing manifold formed separately and independently of said adapter; and receiving the adapter within the lumen of the manifold so as to occupy space within the manifold and reduce the volume within the lumen of the manifold to facilitate flow of the injectable therapeutic substance through the manifold and into the patient's body.

15. 15. The method of claim 14, further comprising providing a tubing element within the lumen of the adapter to maintain patency of the lumen of the adapter and facilitate flow of the injectable therapeutic substance through the lumen of the adapter.

Images