Delivery device

Abstract

The present disclosure provides a device housing microparticles for injectable delivery to a patient using an injectable medium, or for loading with microparticles for injectable delivery to a patient using an injectable medium. The device includes: a fluid inlet fluidly connectable to a source of the injectable medium; two parallel fluid flow paths, each flow path is (a) fluidly connected or fluidly connectable to the fluid inlet and (b) fluidly connected or fluidly connectable to the fluid mixer; a fluid mixer fluidly connecting the first and the second fluid flow paths; and a fluid outlet downstream of the fluid mixer. The first fluid flow path includes a receptacle for holding the microparticles. The two parallel fluid flow paths are configured to flow the injectable medium at different flow rates when the injectable medium is provided at the same fluid pressure.

Description

DELIVERY DEVICECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application clams the benefit of priority of United States Provisional Patent Appln No. 63 / 568,257 filed March 21, 2024, which is hereby incorporated by reference.FIELD

[0002] The present disclosure relates to a device for delivering microparticles to a patient.BACKGROUND

[0003] The following paragraphs are not an admission that anything discussed in them is prior art or part of the knowledge of persons skilled in the art.

[0004] Microparticles are employed by interventional radiologists for the selective occlusion of blood vessels in the treatment of, for example, hypervascular tumors such as leiomyoma uteri, and vascular anomalies such as vascular malformations. Such microparticles are injected into the vasculature of the tumour in a patient.

[0005] Selective internal radiation therapy (SIRT) may be used to treat primary or metastatic hepatic malignancies. In SIRT, yttrium-90 (90Y) radiolabeled microparticles are injected into a hepatic artery of a patient, preferentially localizing in the hepatic tumours due to their increased vascularization. The radioactive yttrium- 90 labeled microparticles decay and deliver radiation to the surrounding tissue.

[0006] W02020082168 describes a delivery device for loading with microparticles for intravenous delivery to a patient. The device is fluidly couplable to a transport medium and a displacement medium. The device includes: a first fluid inlet fluidly couplable to the transport medium, a fluid outlet, a fluid mixer fluidly coupling the first fluid inlet to the fluid outlet. The device also includes a receptacle configured to hold microparticles, the receptacle fluidly coupled to the fluid mixer. The device further includes a second fluid inlet fluidly couplable to the displacement medium andfluidly coupled to the receptacle, the receptacle fluidly coupling the second fluid inlet to the fluid mixer.INTRODUCTION

[0007] The following introduction is intended to introduce the reader to this specification but not to define any invention. One or more inventions may reside in a combination or sub-combination of the apparatus elements or method steps described below or in other parts of this document. The inventors do not waive or disclaim their rights to any invention or inventions disclosed in this specification merely by not describing such other invention or inventions in the claims.

[0008] Microparticles are injected intravenously into a patient with an injection medium, such as an aqueous intravenous solution. However, when the microparticles have a substantially higher density than the injection medium (such as glass microparticles in an aqueous solution) the microparticles may settle together making it difficult to inject the microparticles into the patient. It may be especially difficult to administer the microparticles at a slow and consistent rate.

[0009] BTG attempts to address this problem with their TheraSphere™ yttrium-90 glass microspheres product by flowing the injection medium up through the bottom of the settled microparticles to generate in the delivery device a fluidized bed of microparticles in a constant volume reservoir. Fluidized microparticles are carried along with the injection medium to the patient. Since the microparticles are significantly more dense than the injection medium, this approach may result in an injection medium with an undesirably high concentration of microparticles being delivered over a short period time.

[0010] There remains a need for a delivery device that, in operation, can be used to intravenously administer microparticles to a patient.

[0011] In a device that includes two parallel flow paths, where microparticles are housed in a substantially vertical receptacle located in one of the flow paths before delivery to the patient, the microparticles would act as a fluid restrictor. Applying a single fluid pressure against both the flow path with the microparticles and the flow path without the microparticles would result in fluid preferentially flowing through the flow path without the microparticles.

[0012] In devices according to the present disclosure, a flow restrictor is included in the flow path without the microparticles. The flow restrictor modulates the pressure between the two parallel flow paths to result in sufficient pressure in the flow path with the microparticles so that the microparticles are displaced into the fluid mixer at a desired rate. Devices according to the present disclosure may be fluidly connectable to a single source of injectable medium, such as a syringe, which may apply a single fluid pressure to the device. The single source of injectable medium may provide the injectable medium to the device at a fluid pressure from about 10 to about 100 psi. The fluid pressure may be a low fluid pressure, such as from about 10 to about 30 psi; a medium fluid pressure, such as about 30 to about 80 psi, for example from about 30 to about 60 psi; or a high pressure, such as from about 80 to about 100 psi.

[0013] In one aspect, the present disclosure provides a device for loading with microparticles for injectable delivery to a patient. The device is fluidly connectable to a source of an injectable medium. The device includes a first fluid inlet fluidly connectable to the source of the injectable medium, a first fluid outlet, and a fluid mixer fluidly coupling the first fluid inlet to the first fluid outlet. The device also includes a second fluid outlet and a second fluid inlet that, when fluidly coupled together, result in the device having a displacement-medium flow path that fluidly coupling the first fluid inlet to the fluid mixer. The displacement-medium flow path includes a receptacle for holding the microparticles. The device also includes a transport-medium flow path distinct from the displacement-medium flow path. The transport-medium flow path fluidly coupling the first fluid inlet to the fluid mixer. The transport-medium flow path includes a transport-medium flow restrictor upstream of the fluid mixer.

[0014] In emother aspect, the present disclosure provides a device housing microparticles for injectable delivery to a patient using an injectable medium, or for loading with microparticles for injectable delivery to a patient using an injectable medium. The device includes: a fluid inlet fluidly connectable to a source of the injectable medium; two parallel fluid flow paths, each flow path is (a) fluidly connected or fluidly connectable to the fluid inlet and (b) fluidly connected or fluidly connectable to the fluid mixer; a fluid mixer fluidly connecting the first and the second fluid flow paths; and a fluid outlet downstream of the fluid mixer. The firstfluid flow path includes a receptacle for holding the microparticles. The two parallel fluid flow paths are configured to flow the injectable medium at different flow rates when the injectable medium is provided at the same fluid pressure and when the device lacks microparticles in the receptacle.

[0015] In still another aspect, the present disclosure provides a device for injectable delivery of microparticles to a patient. The delivery device is fluidly connected to a source of an injectable medium. The delivery device includes: a fluid inlet fluidly connected to the source of the injectable medium; a fluid outlet; a fluid mixer fluidly coupling the fluid inlet to the fluid outlet; a displacement-medium flow path fluidly coupling the fluid inlet to the fluid mixer; and a transport-medium flow path distinct from the displacement-medium flow path, the transport-medium flow path fluidly coupling the fluid inlet to the fluid mixer. The displacement-medium flow path includes a receptacle housing the microparticles. The transport-medium flow path includes a flow restrictor upstream of the fluid mixer. During operation, the injectable medium is split between the displacement-medium flow path and the transportmedium flow path, the injectable medium flowing through the displacement-medium flow path fluidly drives microparticles from the receptacle into the fluid mixer, mixing with the injectable medium flowing from the transport-medium flow path, and delivering the microparticles to the patient via the fluid outlet.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0016] Examples according to the present disclosure will now be described, by way of example only, with reference to the attached Figures. To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced.

[0017] FIG. 1 is an illustration of an exemplary device according to the present disclosure.

[0018] FIG. 2 is a cross-sectional illustration of an exemplary flow restrictor according to the present disclosure.

[0019] FIG. 3 is a cross-sectional illustration of an exemplary unitary combination of a flow restrictor and fluid mixer according to the present disclosure.

[0020] FIG. 4A is an illustration of an exemplary device according to the present disclosure.

[0021] FIG. 4B is an illustration of a three-quarter view of the exemplary device illustrated in FIG. 4A.GLOSSARY OF VARIOUS TERMS

[0022] A "flow path" refers to the route through which a fluid moves, such as from one location in the device to smother location in the device. For example, a device may include a flow path from an inlet to an outlet; or a flow path from a fluid splitter to a fluid mixer. One flow path may be a part of another flow path, for example a flow path from an inlet to an outlet may also include a flow path from a fluid splitter to a fluid mixer. A flow path may be defined by the component or components that allow the fluid to flow therethrough, such as tubing, receptacles, fluid mixers, microparticle traps, and / or flow-rate reducers.

[0023] "Downstream" refers to a relative position in a flow path based on the direction that the injectable medium flows during operation of the device. In a flow path with two components, the downstream component is closer to the outlet of the device. "Upstream" refers to a relative position in a flow path based on the direction that the injectable medium flows during operation of the device. In a flow path with two components, the upstream component is closer to the inlet of the device.

[0024] "Fluid splitter" refers to component or combination of components that allow a fluid in one flow path to flow into two or more different flow paths. For example, a fluid splitter may be a 3 -way connector, such as a Y-set connector, where fluid flowing into the trunk of the Y is split into two flow paths flowing out of the branches of the Y.

[0025] "Fluidly coupling" or “fluidly connecting” refers to joining two other components in fluid communication. The specification may state that a component or combination of components “fluidly couples” or "fluidly connects" the other components. Two components that are capable of being joined in fluid communication may be referred to as “fluidly couplable” or “fluidly connectable”.

[0026] "Injectable medium" refers to a liquid suitable for injection into a patient. The liquid may be an intravenous solution, such as a saline solution or a medical contrast having an osmolality less than or equal to 350 mgl / mL.

[0027] "Loading fluid" refers to a liquid suitable for filling the device before microparticles are loaded therein. The loading fluid may be the same fluid as the injectable medium.

[0028] In the context of the present disclosure, the terms “microparticle” refers to a particle that has a diameter that is less than 1200 pm and that has a density greater than the density of the injectable medium. For a mixture of particles, the mixture has an average diameter that is less than 1200 pm. In some examples, the average diameter may be less than 600 pm. In particular examples, a mixture of microparticles may have an average diameter that is from about 25 pm to about 150 pm.

[0029] "Receptacle" refers to a component or combination of components sized and shaped to house the microparticles when the microparticles are loaded into the device and the device is in a delivery orientation. The receptacle may be, for example, an elongate housing such as tubing. The receptacle may include an elongate housing having an inner diameter that is about 5 to 110 times larger than the average diameter of the microparticles.

[0030] In the context of the present disclosure, a "microparticle trap" refers to a component or combination of components that prevent the microparticles from entering the fluid mixer when no external fluid pressure is being applied to the device and the device is positioned in a delivery orientation. The microparticle trap may include a bend in the flow path, such as a bend that is from about 90° to about 180°.

[0031] "Unitary" refers to two or more components of the device being part of a single, undivided unit, such as being made as a single piece during manufacturing.

[0032] In the context of the present disclosure, a "flow restrictor" a refers to a component or combination of components that hinders the flow of a fluid medium passing through the component or combination of components. Hindering the flow of a fluid generates an upstream static pressure that is higher than the static pressure in the flow restrictor. A flow path that includes a flow restrictor may divert a portion of fluid away from the flow path.

[0033] Examples of a flow restrictor include: a portion of the flow path having a smaller inner diameter than the portion of the flow path immediately upstream of the flow restrictor; one or more obstructions to the fluid flowing through the flow path, such as a filter or a torturous flow path; a portion of the flow path that induces turbulent flow, such as a portion of the flow path with rough sidewalls.

[0034] In the context of the present disclosure, a “fluid mixer” should be understood to refer to any combination of components that mixes the injectable mediums flowing from the two flow paths to the fluid outlet. A fluid mixer may be a 3 -way connector, such as a T-connector, where fluid flows from two flow paths into the two arms of the T, and is dispensed as a mixture from the trunk of the T.

[0035] In the context of the present disclosure, "parallel" flow paths refers to flow paths where incoming fluid is split and travels down the separate flow paths. Fluid flowing in one fluid flow path would not later flow through the other parallel fluid flow path or paths. In parallel flow paths, with all other conditions being equal, restricting the flow of fluid through one of the parallel flow paths results in the fluid preferentially flowing through the other parallel flow path or flow paths. For example, in otherwise identical flow paths, adding a flow restrictor to one path may result in fluid flowing through the unrestricted flow path at a rate that is greater than the rate of the fluid flowing through the restricted flow path.DETAILED DESCRIPTION

[0036] In one aspect, the present disclosure provides a device (A) housing microparticles for injectable delivery to a patient using an injectable medium, or (B) for loading with microparticles for injectable delivery to a patient using an injectable medium. The device includes: a fluid inlet fluidly connectable to a source of the injectable medium; two parallel fluid flow paths, each flow path is (a) fluidly connected or fluidly connectable to the fluid inlet and (b) fluidly connected or fluidly connectable to the fluid mixer; a fluid mixer fluidly connecting the first and the second fluid flow paths; and a fluid outlet downstream of the fluid mixer.

[0037] The first fluid flow path includes a receptacle for holding the microparticles. The two parallel fluid flow paths are configured to flow the injectable medium atdifferent flow rates when the injectable medium is provided at the same fluid pressure and when the device lacks microparticles in the receptacle.

[0038] In some examples, the receptacle may sized to hold about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1 gram, about 1.1 grams, about 1.2 grams, about 1.3 grams, about 1.4 grams, about 1.5 grams, about 2 grams, about 3 grams, about 4 grams, about 5 grams, about 6 grams, about 7 grams, about 8 grams, about 9 grams, or about about 10 g of the microparticles before any of the microparticles are delivered to the patient. In some examples, the receptacle may hold from about 50 mg to about 200 mg of the microparticles before any of the microparticles are delivered to the patient. In other examples, the receptacle may hold from about 200 mg to about 500 mg, about 500 mg to about 1000 mg, or about 1000 mg to about 2000 mg of the microparticles before any of the microparticles are delivered to the patient.

[0039] In another aspect, the present disclosure provides a device for loading with microparticles for injectable delivery to a patient. The device is fluidly connectable to a source of an injectable medium. The device includes a first fluid inlet fluidly connectable to the source of the injectable medium, a first fluid outlet, and a fluid mixer fluidly coupling the first fluid inlet to the first fluid outlet. The device also includes a second fluid outlet and a second fluid inlet that is fluidly couplable to the second fluid outlet. When fluidly coupled together, the second fluid outlet and the second fluid inlet result in the device having a displacement-medium flow path that fluidly connects the first fluid inlet to the fluid mixer. The displacement-medium flow path includes a receptacle for holding the microparticles. The device also includes a transport-medium flow path distinct from the displacement-medium flow path. The transport-medium flow path fluidly coupling the first fluid inlet to the fluid mixer.The transport-medium flow path includes a transport-medium flow restrictor upstream of the fluid mixer.

[0040] In the context of the present disclosure, "displacement medium" refers to the portion of the injectable medium flowing through the flow path that includes, or is configured to include, the microspheres. In operation, when a device according to the present disclosure includes microparticles, the displacement medium helps movemicroparticles from the receptacle to the fluid mixer, where it is mixed with transport medium and delivered to the patient via the outlet. A "displacement-medium flow path" refers to the fluid flow path for the displacement medium.

[0041] In the context of the present disclosure, "transport medium" refers to the portion of the injectable medium flowing through the flow path that lacks the microspheres. In operation, when a device according to the present disclosure includes microparticles, displacement medium carrying microparticles from the receptacle is mixed with the transport medium in the fluid mixer, and the resulting combination is delivered to the patient via the outlet.

[0042] A "transport-medium flow path" refers to the fluid flow path for the transport medium. A "transport-medium" flow restrictor refers to a flow restrictor positioned in the transport medium flow path.

[0043] The first fluid flow path discussed above may be referred to as the displacement-medium flow path. The second fluid flow path discussed above may be referred to as the transport-medium flow path. It should be understood that features discussed below with respect to the transport-medium flow path, such as the transport-medium flow restrictor, are equally applicable to the second fluid flow path of the device above. Similarly, it should be understood that features discussed below with respect to the displacement-medium flow path, such as the displacement-medium flow restrictor, are equally applicable to the first fluid flow path of the device above.

[0044] The transport-medium flow restrictor may include a restricting passage that has an inner diameter that is about 20% to about 30% of the inner diameter of the flow path immediately upstream of the flow restrictor.

[0045] The transport-medium flow restrictor may include a restricting passage having an inner diameter that is from about 0.012 inches to about 0.018 inches when the microparticles have an average diameter from about 25 pm to about 150 pm. For example, the inner diameter may be about 0.015 inches when the microparticles have an average diameter of about 29 pm; the inner diameter may be about 0.013 inches when the microparticles have an average diameter of about 51 pm; the inner diameter may be about 0.015 inches when the microparticles have an average diameter of about 104 pm; or the inner diameter may be about 0.017 inches when the microparticleshave an average diameter of about 145 pm. Microparticles with an average diameter from about 28 to about 30 pm may be used to treat or visualize a hepatocellular carcinoma, such as by delivery of radioactive microparticles or radiopaque microparticles, respectively. Microparticles with an average diameter from about 150 to about 300 pm may be used for middle meningeal artery embolization, such as to treat a chronic subdural hematoma.

[0046] The device may also include a microparticle trap fluidly connecting the receptacle to the fluid mixer. For example, the microparticle trap may include a bend in the tubing that makes up the displacement-medium flow path. The bend may be from about 90° to about 180°.

[0047] The displacement-medium flow path may also include a displacement medium flow restrictor downstream of the receptacle and upstream of the fluid mixer. When the device includes a microparticle trap, the displacement medium flow restrictor is downstream of the microparticle trap. The magnitude of the flow restriction caused by the displacement medium flow restrictor may be selected to be less than the magnitude of the flow restriction caused by the transport medium flow restrictor. In such a device, when the device lacks microparticles and when the injectable medium is provided at the same fluid pressure, the flow rate through the displacement-medium flow path is greater than the flow rate through the transportmedium flow path.

[0048] As microparticles are delivered from a device according to the present disclosure, and the number of microparticles in the receptacle falls, the magnitude of the flow restriction caused by the microparticles is reduced.

[0049] In a device according to the present disclosure that has a flow rate through the displacement-medium flow path that is greater than the flow rate through the transport-medium flow path when the device lacks microparticles and when the injectable medium is provided at the same fluid pressure, as the number of microparticles approaches zero the greater flow rate through the displacementmedium flow path helps displace the remaining microparticles into the mixer and out of the device.

[0050] The displacement medium flow restrictor may include a restricting passage having an inner diameter that is about 40% to about 80% of the inner diameter of the displacement-medium flow path immediately upstream of the flow restrictor.

[0051] The displacement medium flow restrictor may include a restricting passage having an inner diameter that is from about 0.027 inches to about 0.043 inches when the microparticles have an average diameter from about 25 pm to about 150 pm. For example the inner diameter may be about 0.030 inches when the microparticles have an average diameter of about 29 pm; the inner diameter may be about 0.029 inches when the microparticles have an average diameter of about 51 pm; the inner diameter may be about 0.030 inches when the microparticles have an average diameter of about 104 pm; or the inner diameter may be about 0.030 or about 0.041 inches when the microparticles have an average diameter of about 145 pm.

[0052] The displacement medium flow restrictor and the transport-medium flow restrictor may both include restricting passages, and the ratio of the cross-sectional area of the displacement medium flow restrictor to the cross-sectional area of the transport-medium flow restrictor may be from about 3:1 to about 7:1.

[0053] Different combinations of microparticle sizes, receptacle dimensions, flow path dimensions and flow restrictors can provide different flow restrictions through the different flow paths and can result in the microparticles being deliverable at different average concentrations. For example, all other conditions being kept constant:• increasing the transport medium flow path restrictor diameter results in delivery at a lower average concentration;• decreasing the transport medium flow path restrictor diameter results in delivery at an higher average concentration;• increasing the displacement medium flow path restrictor diameter results in delivery at an higher average concentration;• decreasing the displacement medium flow path restrictor diameter results in delivery at an lower average concentration;• increasing the average microparticle diameter results in delivery at an higher average concentration;• decreasing the average microparticle diameter results in delivery at a lower average concentration;• increasing the receptacle diameter results in delivery at a higher average concentration;• decreasing the receptacle diameter results in delivery at a lower average concentration;• increasing the volume of microspheres within the receptacle results in delivery at a lower average concentration; and• decreasing the volume of microspheres within the receptacle results in delivery at a higher average concentration.

[0054] The second fluid outlet may be fluidly couplable to the second fluid inlet via a microparticle-supply conduit engageable with the device. The microparticle-supply conduit may include: an inlet fluidly couplable to the second fluid outlet of the device, an outlet fluidly couplable to the second fluid inlet of the device, a valve between the inlet and the outlet, and a primary container for holding the microparticles. The primary container is in fluid communication with one port of the valve. The valve may be a 3 -way valve.

[0055] The microparticles may be housed in the primary container during transportation, and the microparticle-supply circuit may be provided separately from a device according to the present disclosure. The microparticle-supply conduit may be used to load the microparticles into the device, such as before the device is used to deliver the microparticles to the patient. The inlet and the outlet of the microparticlesupply conduit may be fluidly connected to the second fluid outlet and the second fluid inlet, respectively, and the microparticles housed in the primary container may be allowed to flow down into the receptacle by positioning the device in a loading orientation. The loading orientation of the device may be an angle of about 15° to about 20° off vertical. The microparticles may be prompted to flow into the receptacle by injecting an amount of fluid into the primary container.

[0056] The device may also include a loading fluid inlet upstream of the transportmedium flow path and the displacement-medium flow path. The loading fluid inlet may be in fluid communication with the first fluid inlet. The loading fluid inlet allows for fluid, such as injectable medium, to be drawn into a syringe that is fluidly coupledto the fluid inlet of the device. The loading fluid drawn into the syringe may be used to prime the device before the microparticles are loaded into the receptacle.

[0057] The displacement-medium flow path may be parallel to the transport-medium flow path.

[0058] It should be understood that features discussed above with respect to the transport-medium flow path, such as the transport-medium flow restrictor, are equally applicable to the transport-medium flow path of the device below. Similarly, it should be understood that features discussed above with respect to the displacement-medium flow path, such as the displacement-medium flow restrictor, are equally applicable to the displacement-medium flow path of the device below.

[0059] In still another aspect, the present disclosure provides a device for injectable delivery of microparticles to a patient. In this aspect, the delivery device is set up for delivery of the microparticles out of the device, such as to the patient. The delivery device is fluidly connected to a source of an injectable medium. The delivery device includes: a fluid inlet fluidly connected to the source of the injectable medium; a fluid outlet; a fluid mixer fluidly coupling the fluid inlet to the fluid outlet; a displacementmedium flow path fluidly coupling the fluid inlet to the fluid mixer; and a transportmedium flow path distinct from the displacement-medium flow path, the transportmedium flow path fluidly coupling the fluid inlet to the fluid mixer. The displacement-medium flow path includes a receptacle housing the microparticles. The transport-medium flow path includes a flow restrictor upstream of the fluid mixer. During operation, the injectable medium is split between the displacement-medium flow path and the transport-medium flow path, the injectable medium flowing through the displacement-medium flow path fluidly drives microparticles from the receptacle into the fluid mixer, mixing with the injectable medium flowing from the transportmedium flow path, and delivering the microparticles to the patient via the fluid outlet.

[0060] Specific combinations (Examples 1 to 6) of different features disclosed above are shown in Tables 1 to 3. Examples 1 to 6 of Tables 1 to 3 relate to six specific devices.

[0061] Table 1 - Microparticle sizes and microparticle receptacle

[0062] Table 2 - Displacement-medium flow path

[0063] Table 3 - Transport-medium flow path

[0064] One particular example of a device according to the present disclosure is illustrated in FIG. 1. Device 100 is fluidly connected to a source of injectable medium 102, illustrated as a syringe, via first fluid inlet 104. The device 100 also includes a first fluid outlet 106. The fluid inlet 104 and the fluid outlet 106 are fluidly coupled by a fluid mixer 108. The device 100 also includes a second fluid outlet 110 and a second fluid inlet 112. Inlet 110 and outlet 112 are fluidly connectable through a microparticle-supply conduit, not shown. When inlet 110 and outlet 112 are fluidly connected, such as by a microparticle-supply circuit (not shown) device 100 includes a displacement-medium flow path 114. When inlet 110 and outlet 112 are not fluidly connected, the device 100 may be considered to have a flow path that is (a) fluidly connectable to the fluid inlet and (b) fluidly connectable to the fluid mixer.

[0065] The device 100 also includes a fluid splitter 116, which splits the incoming fluid between the displacement-medium flow path 114 and a transport-medium flow path 118. The transport-medium flow path 118 includes a transport-medium flow restrictor 120. The displacement-medium flow path 114 includes a receptacle 122 for housing the microparticles, a displacement-medium flow restrictor 124, and a microparticle trap 126. The flow restrictor 124 is located in one arm of the fluid mixer 108, and is unitary with the mixer 108. The device 100 also includes a loading fluid inlet 128, which is in fluid communication with the source of injectable medium 102.

[0066] During operation, inlet 110 and outlet 112 are fluidly connected and receptacle 122 houses the microparticles. Injectable medium from 102 is injected into the inlet 104 by the syringe and flows into the fluid splitter 116. The injectable medium is split between the displacement-medium flow path 114 and the transportmedium flow path 118. Injectable medium flowing through the displacement-medium flow path 114 moves microparticles towards the fluid mixer 108. Injectable medium flowing through the transport-medium flow path 118 mixes with the displacement medium and the microparticles from the flow path 114. The resulting mixture travels from the fluid mixer 108 and out of the device via the fluid outlet 106.

[0067] Microparticles in the receptacle 112 may act as a fluid flow restrictor. In a device without the transport-medium flow restrictor 120, a sufficient number of particles packed into the receptacle 122 may result in sufficient flow restriction in the flow path 114 that fluid preferentially travels through the transport-medium flow path118 and no microparticles are delivered from the device. The transport-medium flow restrictor 120 rebalances the relative fluid pressures between the two flow paths 114 and 118, which allows the displacement medium to move microparticles towards the fluid mixer 108.

[0068] An illustration of an exemplary transport-medium flow restrictor 120 is illustrated in FIG. 2. The flow restrictor 120 includes a fluid inlet 202, a fluid outlet 204, and a constricting passage constricting passage 206.

[0069] An illustration of an exemplary unitary combination of flow restrictor 124 and flow mixer 108 is illustrated in FIG. 3. The combination 300 is illustrated as a T- connector, with a first inlet arm 302 fluidly connecting to the transport-medium flow path 118, and a second inlet arm 304 fluidly connecting to the displacement-medium flow path 114. The combination 300 includes a constricting passage 306. Injectable medium from the two flow paths, 114 and 118, mix and travel out the outlet arm 308.

[0070] Another particular example of a device according to the present disclosure is illustrated in FIG. 4A. The device of FIG. 4A is illustrated in three-quarter view in FIG. 4B. Device 400 is fluidly connectable to a source of injectable medium (not shown) via first fluid inlet 104. Device 400 also includes a first fluid outlet 106 and a fluid mixer 108. The device 400 also includes a fluid splitter 116 (not shown in FIG. 4A but visible in FIG. 4B). The fluid splitter 116 splits the incoming fluid between a displacement-medium flow path 114 and a transport-medium flow path 118.

[0071] The transport-medium flow path 118 includes a transport-medium flow restrictor 120. The transport-medium flow path 118 fluidly connects the first fluid inlet 104 to the fluid mixer 108.

[0072] The displacement-medium flow path 114 includes a receptacle 122, a displacement-medium flow restrictor 124, and a microparticle trap 126. Device 400 includes a 3-way valve 402 in the displacement-medium flow path 114. The 3-way valve 402 allows microparticles to be loaded into the receptacle 122 via fluid inlet 404. The 3 -way valve 402 allows the displacement-medium flow path 114 to fluidly connect the first fluid inlet 104 to the fluid mixer 108 when the valve is in an operating position.

[0073] During operation, receptacle 122 houses the microparticles. Injectable medium is injected into the inlet 104 and is split by the fluid splitter 116 between the displacement-medium flow path 114 and the transport-medium flow path 118. Injectable medium flowing through the displacement-medium flow path 114 travels through the 3-way valve 402, into the receptacle 122, and moves microparticles towards the fluid mixer 108. Injectable medium flowing through the transport-medium flow path 118 mixes with the displacement medium and the microparticles from the flow path 114. The resulting mixture travels from the fluid mixer 108 and out of the device via the fluid outlet 106.

[0074] Microparticles in the receptacle 112 may act as a fluid flow restrictor. In a device without the transport-medium flow restrictor 120, a sufficient number of particles packed into the receptacle 122 may result in sufficient flow restriction in the flow path 114 that fluid preferentially travels through the transport-medium flow path 118 and no microparticles are delivered from the device. The transport-medium flow restrictor 120 rebalances the relative fluid pressures between the two flow paths 114 and 118, which allows the displacement medium to move microparticles towards the fluid mixer 108.

[0075] Examples

[0076] The specific combinations of features identified in Example 1 was tested using 600 mg of microparticles with an average size of 29 pm. Example 2 was tested using 200 mg of microparticles with an average size of 29 pm. Example 3 was tested using 1250 mg of microparticles with an average size of 51 pm. Example 4 was tested using 1250 mg of microparticles with an average size of 104 pm. Example 5 was tested using 1250 mg of microparticles with an average size of 145 pm. Examples 1-5 were tested using 0.9% saline solution as the injectable medium. The results are shown in Table 4. Examples 1 and 2 were tested using the device illustrated in FIG. 4A and FIG. 4B. Examples 3, 4 and 5 were tested using the device illustrated in FIG.1 using saline delivered at a constant rate of 20 mL / min.

[0077] Table 4

[0078] In the preceding description, for purposes of explanation, numerous details are set forth in order to provide a thorough understanding of the examples. However, it will be apparent to one skilled in the art that these specific details are not required. Accordingly, what has been described is merely illustrative of the application of the described examples and numerous modifications and variations are possible in light of the above teachings. Other technical features may be readily apparent to one skilled in the art from the figures, descriptions, and claims.

[0079] Since the above description provides examples, it will be appreciated that modifications and variations can be effected to the particular examples by those of skill in the art. Accordingly, the scope of the claims should not be limited by the particular examples set forth herein, but should be construed in a manner consistent with the specification as a whole.

Claims

CLAIMSWhat is claimed is:

1. A device for loading with microparticles for injectable delivery to a patient, the device being fluidly connectable to a source of an injectable medium, the device comprising: a first fluid inlet fluidly connectable to the source of the injectable medium; a first fluid outlet; a fluid mixer fluidly coupling the first fluid inlet to the first fluid outlet; a second fluid outlet and a second fluid inlet that, when fluidly coupled together, result in the device having a displacement-medium flow path that fluidly coupling the first fluid inlet to the fluid mixer, the displacement-medium flow path comprising a receptacle for holding the microparticles; and a transport-medium flow path distinct from the displacement-medium flow path, wherein the transport-medium flow path fluidly coupling the first fluid inlet to the fluid mixer, and wherein the transport-medium flow path comprises a transportmedium flow restrictor upstream of the fluid mixer.

2. The device of claim 1, wherein the transport-medium flow restrictor comprises a restricting passage having an inner diameter that is about 20% to about 30% of the inner diameter of the flow path immediately upstream of the flow restrictor.

3. The device of claim 1 or 2, wherein the transport-medium flow restrictor comprises a restricting passage having an inner diameter that is from about 0.012 inches to about 0.018 inches when the microparticles have an average diameter from about 25 pm to about 150 pm; for example wherein the inner diameter is about 0.015 inches when the microparticles have an average diameter of about 29 pm; the inner diameter is about 0.013 inches when the microparticles have an average diameter of about 51 pm; the inner diameter is about 0.015 inches when the microparticles have an average diameter of about 104 pm; orthe inner diameter is about 0.017 inches when the microparticles have an average diameter of about 145 pm.

4. The device of any one of claims 1 to 3, further comprising a microparticle trap fluidly connecting the receptacle to the fluid mixer, for example wherein the microparticle trap includes a bend in the displacement-medium flow path that is from about 90° to about 180°.

5. The device of any one of claims 1 to 4, wherein the displacement-medium flow path further comprises a displacement medium flow restrictor downstream of the receptacle and upstream of the fluid mixer, wherein, when dependent from claim 4, the displacement medium flow restrictor is downstream of the microparticle trap.

6. The device of claim 5, wherein the displacement medium flow restrictor comprises a restricting passage having an inner diameter that is about 40% to about 80% of the inner diameter of the displacement-medium flow path immediately upstream of the flow restrictor.

7. The device of claim 5 or 6, wherein the displacement medium flow restrictor comprises a restricting passage having an inner diameter that is from about 0.027 inches to about 0.043 inches when the microparticles have an average diameter from about 25 pm to about 150 pm; for example wherein the inner diameter is about 0.030 inches when the microparticles have an average diameter of about 29 pm; the inner diameter is about 0.029 inches when the microparticles have an average diameter of about 51 pm; the inner diameter is about 0.030 inches when the microparticles have an average diameter of about 104 pm; or the inner diameter is about 0.030 or about 0.041 inches when the microparticles have an average diameter of about 145 pm.

8. The device of any one of claims 5 to 7, wherein the displacement medium flow restrictor and the transport-medium flow restrictor both comprises restrictingpassages, and the ratio of the cross-sectional area of the displacement medium flow restrictor to the cross-sectional area of the transport-medium flow restrictor is from about 3:1 to about 7:1.

9. The device of any one of claims 1 to 8, wherein the second fluid outlet is fluidly couplable to the second fluid inlet via a microparticle-supply conduit engageable with the device, wherein the microparticle-supply conduit comprises: an inlet fluidly couplable to the second fluid outlet of the device, an outlet fluidly couplable to the second fluid inlet of the device, a valve, such as a 3 -way valve, between the inlet and the outlet, and a primary container for holding the microparticles, wherein the primary container is in fluid communication with one port of the valve.

10. The device of any one of claims 1 to 9, wherein the receptacle comprises an elongate housing having an inner diameter that is about 5 to about 110 times larger than the average diameter of the microparticles.

11. The device of any one of claims 1 to 10, further comprising a loading fluid inlet upstream of the transport-medium flow path and the displacement-medium flow path, the loading fluid inlet in fluid communication with the first fluid inlet.

12. The device of any one of claims 1 to 11, wherein the displacement-medium flow path is parallel to the transport-medium flow path.

13. A device housing microparticles for injectable delivery to a patient using an injectable medium, or for loading with microparticles for injectable delivery to a patient using an injectable medium, the device comprising: a fluid inlet fluidly connectable to a source of the injectable medium; two parallel fluid flow paths, each flow path is (a) fluidly connected or fluidly connectable to the fluid inlet and (b) fluidly connected or fluidly connectable to the fluid mixer, wherein the first fluid flow path comprises a receptacle for holding the microparticles, and wherein the two parallel fluid flow paths are configured to flowthe injectable medium at different flow rates when the injectable medium is provided at the same fluid pressure; a fluid mixer fluidly connecting the first and the second fluid flow paths; and a fluid outlet downstream of the fluid mixer.

14. The device of claim 13, wherein the flow rate through the first fluid flow path is greater than the flow rate through the second fluid flow path when the receptacle does not house microparticles.

15. The device of claim 13, wherein the second fluid flow path comprises a flow restrictor, such as a constricting passage.

16. The device of claim 15, wherein the flow restrictor in the second fluid flow path comprises a restricting passage having an inner diameter that is about 20% to about 30% of the inner diameter of the second fluid flow path immediately upstream of the flow restrictor.

17. The device of claim 16, wherein the flow restrictor in the second fluid flow path comprises a restricting passage having an inner diameter that is from about 0.012 inches to about 0.018 inches when the microparticles have an average diameter from about 25 pm to about 150 pm; for example wherein the inner diameter is about 0.015 inches when the microparticles have an average diameter of about 29 pm; the inner diameter is about 0.013 inches when the microparticles have an average diameter of about 51 pm; the inner diameter is about 0.015 inches when the microparticles have an average diameter of about 104 pm; or the inner diameter is about 0.017 inches when the microparticles have an average diameter of about 145 pm.

18. The device of any one of claims 13 to 17, further comprising a microparticle trap fluidly connecting the receptacle to the fluid mixer, for example wherein the microparticle trap includes a bend in the first fluid flow path that is from about 90° to about 180°.

19. The device of any one of claims 15 to 18, wherein the first fluid flow path further comprises a flow restrictor downstream of the receptacle and upstream of the fluid mixer, wherein, when dependent from claim 18, the flow restrictor in the first fluid flow path is downstream of the microparticle trap.

20. The device of claim 19, wherein the flow restrictor in the first fluid flow path comprises a restricting passage having an inner diameter that is about 40% to about 80% of the inner diameter of the first fluid flow path immediately upstream of the flow restrictor.

21. The device of claim 19 or 20, wherein the flow restrictor in the first fluid flow path comprises a restricting passage having an inner diameter that is from about 0.027 inches to about 0.043 inches when the microparticles have an average diameter from about 25 pm to about 150 pm; for example wherein the inner diameter is about 0.030 inches when the microparticles have an average diameter of about 29 pm; the inner diameter is about 0.029 inches when the microparticles have an average diameter of about 51 pm; the inner diameter is about 0.030 inches when the microparticles have an average diameter of about 104 pm; or the inner diameter is about 0.030 or about 0.041 inches when the microparticles have an average diameter of about 145 pm.

22. The device of any one of claims 19 to 21, wherein the ratio of the cross-sectional area of the flow restrictor in the second fluid flow path to the cross-sectional area of the flow restrictor in the first fluid flow path is from about 3:1 to about 7:1.

23. The device of any one of claims 13 to 22, wherein the receptacle comprises an elongate housing having an inner diameter that is about 5 to about 110 times larger than the average diameter of the microparticles.

24. The device of any one of claims 13 to 23, further comprising a loading fluid inlet upstream of the second fluid flow path and the first fluid flow path, the loading fluid inlet in fluid communication with the first fluid inlet.

25. The device of any one of claims 13 to 24, comprising the microparticles in the receptacle, preferably wherein the microparticles have an average diameter from about 25 pm to about 150 pm.

26. A device for injectable delivery of microparticles to a patient, the delivery device being fluidly connected to a source of an injectable medium, the delivery device comprising: a fluid inlet fluidly connected to the source of the injectable medium; a fluid outlet; a fluid mixer fluidly coupling the fluid inlet to the fluid outlet; a displacement-medium flow path fluidly coupling the fluid inlet to the fluid mixer, the displacement-medium flow path comprising a receptacle housing the microparticles; a transport-medium flow path distinct from the displacement-medium flow path, the transport-medium flow path fluidly coupling the fluid inlet to the fluid mixer, the transport-medium flow path comprising a flow restrictor upstream of the fluid mixer; wherein, during operation, the injectable medium is split between the displacement-medium flow path and the transport-medium flow path, the injectable medium flowing through the displacement-medium flow path fluidly drives microparticles from the receptacle into the fluid mixer, mixing with the injectable medium flowing from the transport-medium flow path, and delivering the microparticles to the patient via the fluid outlet.

27. The device of claim 26, further comprising a microparticle trap fluidly connecting the receptacle to the fluid mixer, for example wherein the microparticle trap includes a bend in the displacement-medium flow path that is from about 90° to about 180°.

28. The device of claim 26 or 27, wherein the displacement-medium flow path further comprises a displacement medium flow restrictor downstream of the receptacle and upstream of the fluid mixer, wherein, when dependent from claim 27, the displacement medium flow restrictor is downstream of the microparticle trap.

29. The device of any one of claims 26 to 28, wherein the displacement-medium flow path is parallel to the transport-medium flow path.

30. The device of any one of claims 1 to 29, wherein the mixer is unitary with at least one flow restrictor.

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