WO2014015377A1

WO2014015377A1 - Lymphatic access system

Info

Publication number: WO2014015377A1
Application number: PCT/AU2013/000822
Authority: WO
Inventors: David Sullivan
Original assignee: Lymphatech Pty Ltd
Priority date: 2012-07-24
Filing date: 2013-07-24
Publication date: 2014-01-30

Abstract

Described is a lymphatic access system including a lymph reservoir for containing lymph, the lymph reservoir configured to allow access to lymph in the lymph reservoir, an inlet configured to divert lymph from a lymph duct in a subject to the lymph reservoir, an outlet configured to allow lymph in the lymph reservoir to return to a vessel in the subject, and a valve configured to control flow of lymph of the subject to or from the lymph reservoir.

Description

LYMPHATIC ACCESS SYSTEM

Technical Field

[001] The present invention relates to a lymphatic access system configured to direct lymph from a lymph duct in a subject to a lymph reservoir to allow access to the lymph in the lymph reservoir. In particular the present invention relates to an implantable lymphatic access device.

Background

[002] Typical vascular access systems are surgically implanted to allow intermittent access to an artery or vein to allow the withdrawal of blood and the administration of fluids or medications. Typically such devices include a chamber having an outlet connected by a cannula to an artery or vein and a penetrable membrane for the chamber. The penetrable membrane is typically rubber or silicone and in use a needle is passed through the membrane into the chamber allowing fluid to be drawn through the needle or administered into the chamber through the needle.

[003] Lymph is a fluid formed by the draining of interstitial fluid into lymph capillaries. Lymph travels through lymph ducts to lymph nodes before joining larger lymph trunks, such as the thoracic duct, which drain into the circulation via major veins such as the left subclavian vein.

[004] The lymphatic system consists of the lymph capillaries, lymph ducts and lymph nodes. The lymphatic system may transport bacteria, which are captured and destroyed in lymph nodes. Metastatic cancer cells may also be transported via lymph.

[005] Lymph also transports fats from the digestive system. Lymph formed in the digestive system is also known as chyle and typically has a milky white appearance due to presence of triglycerides (fat) contained in spherical lipoproteins known as chylomicrons. Chyle is one of the primary means by which dietary fat enters the circulation.

[006] Filariasis of the lymphatics, where a nematode parasite blocks one or more lymph vessels can lead to a chyluria. Chyluria involves the presence of chyle in the urine resulting from blockage of the lymph vessels by the parasite or from a fistulous communication between the urinary and lymphatic vessels. [007] Lymph also contains lymphocytes. Lymph present in lymph nodes is typically richer in lymphocytes than lymph that has yet to reach the lymph nodes. Lymphocytes are mediators of the mammalian immune system.

[008] The network of lymph vessels that returns lymph to the circulation is an open system with no active pump. Thus lymph is not under pressure comparable to blood in the venous or arterial systems. Lymph movement is facilitated by peristalsis, valves in the lymph vessels, nearby arterial pulsation and movement of adjacent skeletal muscles.

[009] Usually, lymph does not flow backwards along the vessels because of the presence of valves. However if excessive pressure is applied to a lymph vessel, or pressure develops in the lymph system, this can contribute to edema.

[010] Typical vascular access systems are surgically implanted to allow intermittent access to an artery or a vein to allow the withdrawal of blood and the administration of fluids or medications. Typically such devices include a chamber (or 'reservoir¹) having an outlet connected by a conduit to an artery or vein. The chamber also has a penetrable membrane which is typically rubber or silicone and, in use, a needle is passed through the membrane into the chamber allowing fluid to be withdrawn via the needle or administered into the chamber through the needle. The chamber may be located external to the body, or it may be implanted to allow subcutaneous access. Usually, the vascular access system does not separate and prevent the mixing of inwardly and outwardly flowing materials.

[011] Lymph can be accessed by penetration of the axillary or inguinal lymph nodes by long needles or by surgical access to the thoracic duct or other portions of the lymph vessels. These methods are unsuitable for regular access to lymph. Penetration of lymph nodes yields only a small volume of lymph and is ineffective for administering fluid to the lymphatic system, and can cause significant discomfort to the subject.

[012] Accordingly, there is a need for a system that allows intermittent, periodic or continuous access to lymph without requiring repeated surgical procedures. Separation of inwardly and outwardly flowing materials to prevent mixing could be advantageous in some situations.

[013] The present inventors have developed a lymphatic access system. Summary of Invention

[014] In a first aspect there is provided a lymphatic access system comprising:

a lymph reservoir for containing lymph, the lymph reservoir configured to allow access to lymph in the lymph reservoir;

an inlet configured to divert lymph from a lymph duct in a subject to the lymph_s reservoir;

an outlet configured to allow lymph in the lymph reservoir to return to a vessel in the subject; and

a valve configured to control flow of lymph of the subject to or from the lymph reservoir.

[015] Preferably the lymphatic access system comprises an access fitting to allow access to lymph in the lymph reservoir.

[016] The access fitting may be a self-sealing membrane such as a septum, a cap or lid, a fitting for a syringe such as a male or female luer lock fitting. The access fitting may be associated with a further conduit. The further conduit may be configured to connect to a vessel at one end. The further conduit may be associated with a valve, for example to seal the further conduit when not in use.

[017] In some embodiments, several valves can be used in the system to control flow of lymph.

[018] The valve may be a ball valve, a butterfly valve, a pinch valve, an inflatable cuff, a gate valve, a diaphragm valve, a needle valve, or a check valve. Preferably the valve is a unidirectional valve.

[019] In some embodiments the lymphatic access system comprises a pressure release valve.

[020] Preferably the inlet includes an inlet conduit configured to connect to a lymph duct of a subject at one end and divert lymph from the lymph duct of the subject to the lymph reservoir.

[021] Preferably the inlet conduit is configured to connect to a lymph duct by anastomosis with the duct, catheterisation of the duct, or insertion into the duct.

[022] The inlet may be connected to a stent configured for placement within a lymph duct or secured by an exterior collar to a lymph duct, for example the thoracic duct. [023] Preferably the outlet includes an outlet conduit configured to connect to a vessel of a subject at one end and allow lymph from the lymph reservoir to return to a vessel of the subject.

[024] Preferably the outlet conduit is configured to be connected to a vessel by an anastomosis with the vessel, catheterisation of the vessel or insertion into the vessel.

[025] The outlet may be connected to a stent configured for placement within a lymph duct or other vessel or secured by an exterior collar to the lymph duct or vessel.

[026] The vessel may be a lymph duct, vein or ureter.

[027] In one embodiment the lymph reservoir has two or more compartments capable of receiving lymph.

[028] In another embodiment the lymphatic access system includes a second reservoir in fluid communication with the first lymph reservoir.

[029] In another embodiment, the second reservoir is configured to allow access to lymph in the second reservoir.

[030] Preferably the second reservoir includes an access fitting associated with the second reservoir to allow access to lymph in the second lymph reservoir.

[031] In a preferred form the second reservoir includes:

an inlet configured to receive lymph from the first lymph reservoir; and an outlet configured to allow lymph to be removed from the second reservoir.

[032] Preferably the outlet includes a conduit configured to connect to a vessel of a subject at one end and allow lymph from the second reservoir to return to a vessel of the subject.

[033] In one embodiment the second reservoir includes a valve configured to control flow of lymph to or from the second reservoir.

[034] The lymph reservoir or the second reservoir may comprise more than one chamber. For example, the lymph reservoir and/or the second reservoir may be divided by at least one valve, partition, baffle, or any combination thereof.

[035] The lymphatic access system can be made from any suitable biocompatible material. Typically the material will possess sufficient resilience to resist damage from needles or other devices that may be repeatedly inserted into the access system to access the lymph. Examples of biocompatible materials include plastics and metals. Biocompatible plastics are advantageous as they can be used with conventional fabrication techniques. Preferably, the lymph reservoir is constructed from an elastomeric material capable of withstanding repeated punctures with a needle without leaking and which preferably seals after the needle is removed.

[036] In one embodiment the lymphatic access system may be implantable in a subject.

[037] In another embodiment the lymphatic access system, is configured for subcutaneous implantation in a subject.

[038] In one embodiment the lymphatic access system is configured for percutaneous use.

[039] Preferably the subject is a mammal. The mammal preferably is a human, sheep, pig, rabbit or rat.

[040] In a second aspect the present invention provides a kit comprising:

a lymphatic access system according to the first aspect of the present invention; and

at least one catheter configured to provide fluid communication between a lymph duct in a subject and the lymph reservoir of the lymphatic access system.

[041] In a third aspect the present invention provides a method for diverting lymph from a subject, the method comprising:

connecting a lymphatic access system according to the first aspect of the present invention to a lymph duct of a subject; and

diverting lymph from the subject to the lymph reservoir of the lymphatic access system;

accessing lymph in the lymph reservoir; and

returning the lymph to a vessel in the subject.

[042] The lymph may or may not have been processed before being returned to the subject.

[043] In a preferred form, lymph in the reservoir is accessed through an access fitting of the reservoir.

[044] In a preferred form, at least some lymph in the lymph reservoir is returned to the subject via the outlet. [045] The lymph may be returned to the lymphatic system via a lymph vessel or diverted to the venous or urinary system for natural processing and removal from the subject.

[046] In a preferred method the lymph accessed from the lymph reservoir is separated, fractionated, refined, or purified.

[047] In one embodiment the diverted lymph within the lymph reservoir is separated, fractionated, refined, metabolised, purified, and or altered by pharmacological, biochemical, centrifugal and or molecular means prior to returning the lymph.

[048] In one embodiment the accessed lymph is altered by pharmacological, biochemical, physical or molecular means. The pharmacological alteration includes drug treatment, immuno-therapy, or transfection of a biological material.

[049] Preferably the lymph within the lymph reservoir is diverted in order to diagnose or respond to the presence of a pathological disease or condition. The pathological disease or condition is selected from the group consisting of cardiovascular disease,

hyperlipidaemia, diabetes, infectious disease, obesity, metabolic syndrome associated with obesity, organ failure, autoimmune disease, transplant rejection, malignancies including de novo or recurrent malignancies, neurodegenerative diseases, organ failure, sepsis, shock lung, and food allergies.

[050] In one embodiment the neurodegenerative disease is Alzheimer's disease or dementia.

In one embodiment the organ failure is kidney failure, cardiac failure or liver failure.

[051] Preferably the pharmacological alteration includes incorporation of a drug, transfection of a biological material or immuno-therapy.

[052] In one embodiment, the present invention relates to a system for accessing and processing lymph. The system is configured to direct lymph from a lymph vessel in a subject in a controlled fashion to allow acquisition and processing of the lymph with the option of returning some or all of the processed lymph to the subject. In general the system may include a component to access lymph including a device or devices to facilitate physical access to the lymphatic portion of the vasculature, for example a stent. The system also includes conduits and accessible reservoir(s) to facilitate acquisition of the contained lymphatic fluid.. Furthermore, the system may include processing components described in greater detail below. These processing components can assist in processing the lymph for therapeutic purposes. The apparatus may be positioned external to a subject. The apparatus may be located subcutaneously for percutaneous use. That is any or all of the components comprising the system may be implantable and interchangeable.

[053] Throughout this specification, unless the context requires otherwise, the word 'comprise', or variations such as 'comprises' or 'comprising', will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. Thus, in the context of this specification, the term 'comprising' means 'including principally, but not necessarily solely'.

[054] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention, in Australia or elsewhere, before the priority date of each claim of this specification.

[055] In order that the present invention may be more clearly understood, preferred embodiments will be described with reference to the following drawings and examples.

Brief Description of the Drawings

[056] Figure 1 is a schematic view of an embodiment of the lymphatic access system of the invention.

[057] Figure 2 is a schematic view of an embodiment of the lymphatic access system of the invention.

[058] Figure 3 is a schematic view of an embodiment of the lymphatic access system of the invention showing a reservoir having two compartments.

[059] Figure 4 is a schematic view of an embodiment of the lymphatic access system of the invention with two reservoirs.

[060] Figure 5 is a schematic view of an embodiment of the lymphatic access system of the invention for percutaneous or transvenous use that obviates the need for a transmural connection. Definitions

[061] The following are some definitions that may be helpful in understanding the description of the present invention. These are intended as general definitions and should in no way limit the scope of the present invention to those terms alone, but are put forth for a better understanding of the following description.

[062] Unless the context requires otherwise or specifically stated to the contrary, integers, steps, or elements of the invention recited herein as singular integers, steps or elements clearly encompass both singular and plural forms of the recited integers, steps or elements.

[063] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps, features, compositions and compounds.

(064] The term 'access system' as used in this specification refers to a device used to divert or permit flow of a fluid from one region back to another region within the same fluid conduit.

[065] The term 'valve' as used in this specification refers to any device for controlling the passage of fluid.

[066] The term 'pressure release valve' as used in this specification refers to any device for controlling the passage of fluid in response to pressure.

[067] The term 'stent' as used in this specification refers a tubular support device.

[068] In the context of this specification, the term 'subject' includes humans and individuals of any species of social, economic or research importance including but not limited to members of the genus ovine, bovine, equine, porcine, feline, canine, primates (including human and non-human primates), rodents, murine, caprine, leporine, and avian. In preferred embodiments the subject is a human.

Detailed Description of Embodiments of the Invention

[069] With reference to the Figures a lymphatic access system 10 is provided.

[070] The lymphatic access system 10 includes a lymph reservoir 12 for containing lymph. The lymph reservoir 12 includes inlet 14 configured to direct lymph from a lymph duct in a subject to the lymph reservoir 12. In use, the inlet 14 provides fluid

communication between the lymph duct in the subject and the lymph reservoir 12. Typically the lymph reservoir 12 is accessible, for example by use of a needle. In some embodiments there is an access fitting 16 associated with the lymph reservoir 12 which allows access to lymph in the lymph reservoir 12. The lymph reservoir 12 also includes an outlet 18 configured to allow lymph to return to a vessel in the subject. In use, the outlet 18 provides fluid communication between the lymph reservoir 12 and a vessel in the subject. The lymphatic access system 10 can also include a valve 20 to control flow of lymph of the subject to or from the lymph reservoir 12. In some embodiments the lymphatic access system 0 also includes a pressure release valve 22.

[071] The lymphatic access system 10 may be made from any suitable biocompatible material. Typically the material will possess sufficient resilience to resist damage from needles or other devices that may be repeatedly inserted into the access system to access the lymph. Examples of biocompatible materials include plastics and metals. Biocompatible plastics are advantageous as they can be used with conventional fabrication techniques. Preferably, the lymph reservoir 2 is constructed from an elastomeric material capable of withstanding repeated punctures with a needle without leaking and which preferably seals after the needle is removed.

[072] Typically, the inlet 14 includes a conduit 24 to connect to a lymph duct of a subject at one end and divert lymph from the lymph duct of the subject to the lymph reservoir 12. The outlet 18 typically includes an outlet conduit 26 configured to connect to a vessel of a subject at one end and allow lymph from the lymph reservoir 12 to return to the vessel of the subject.

[073] The lymph reservoir 12 may have two or more compartments 28 capable of receiving lymph. For example, as illustrated in Figure 3, the lymph reservoir 2 has compartments 28 formed by the presence of one or more valves, partitions, baffles, support structures 30 or any combination thereof.

[074] In another embodiment, for example as illustrated in Figure 4, the access system 10 includes a second reservoir 32 in fluid communication with the lymph reservoir 12. In a preferred embodiment, the second reservoir 32 includes an inlet 34 configured to receive lymph from the lymph reservoir 12 and an outlet 18 configured to allow lymph to be removed from the second reservoir 32. The second reservoir 32 may be connected to the lymph reservoir 12 by a conduit 38. Alternatively, the outlet 18 may be connected to the inlet 34 of the second reservoir 32. [075] In one embodiment the second reservoir 32 includes a valve 40 configured to control flow of lymph to or from the second reservoir 32.

[076] The reservoir may be any volume considered useful by those skilled in the art. Preferred reservoir volumes are between 5 ml and 500 ml. For example the reservoir volume may be about 5 ml, or about 25 ml, or about 50 ml, or about 75 ml, or about 100 ml, or about 125 ml, or about 150 ml, or about 175 ml, or about 200 ml, or about 225 ml, or about 250 ml, or about 275 ml, or about 300 ml, or about 325 ml, or about 350 ml, or about 375 ml, or about 400 ml, or about 425 ml, or about 450 ml, or about 475 ml, or about 500 ml.

[077] The length of the conduits is typically between about 10 cm and 1 meter. For example the conduit length may about 10 cm, or about 20 cm, or about 30 cm, or about 40 cm, or about 50 cm, or about 60 cm, or about 70 cm, or about 80 cm, or about 90 cm, or about 1 meter. The length may be altered by any means known in the art to suit the anatomy of the subject to which the lymphatic access system 10 is provided.

[078] The lumen size of the conduits is typically between about 1 mm and about 4 mm. For example, the lumen size may be about 1 mm, or about 1.5 mm, or about 2 mm, or about 2.5 mm, or about 3 mm, or about 3.5 mm, or about 4 mm.

[079] In the context of this specification the subject may be an animal. Preferably, the subject is a mammal. The term 'mammal' includes humans and individuals of any species of social, economic or research importance including but not limited to members of the genus ovine, bovine, equine, porcine, feline, canine, primates (including human and non-human primates), rodents, murine, caprine, leporine, and avian. In preferred embodiments the mammal is a human. The lymphatic access system 10 is also suitable for animals such as laboratory animals including mice, rats, rabbits, dogs, sheep, pigs and cows for medical or veterinary research use.

[080] The lymphatic access system 10 may be provided to a subject using minimally invasive techniques known in the art and preferably with the assistance of magnetic resonance imaging (MRI) to reveal the course of the lymphatic duct in the subject. The lymphatic access system 10 may be assembled during installation into the subject. For example, in Figure 1 the inlet conduit 24 may be connected to the lymph duct before connection to the inlet of the lymph reservoir 12. The outlet 18 may then be connected to a vessel directly or via an outlet conduit 26. It is envisaged that where the lymphatic access system 10 is assembled during installation in the body, the order of assembly of the components will be at the discretion of the physician performing the implantation to achieve optimum placement of the lymphatic access system. [081] After installation of the lymphatic access system 10, confirmation that the lymphatic access system 10 is operating may be achieved by for example MRI or by testing the lymphatic access system 10 by removal of lymph from the lymph reservoir 12.

[082] In use, the lymphatic access system 10 can be implantable in a subject and typically surgically implanted, preferably such that it is entirely subcutaneous. For example the lymphatic access system 10 may be fully implantable into the subject such that the access fittings, and/or reservoir(s) are located subcutaneously so as to allow access to the lymph in the reservoir through the skin for example using a needle. That is, the lymph reservoir 12 and/or the second reservoir 32 may be configured for percutaneous use. In preferred embodiments the lymphatic access system 10 is implanted in the extra-thoracic region of a subject and the inlet conduit 24 is connected to the thoracic duct. In this embodiment the outlet conduit 26 may be connected to the junction of the left jugular and subclavian veins.

[083] In one embodiment the lymphatic access system 10 is configured such that the lymph reservoir 12 and/or the second reservoir 32 are external to a subject. For example, the inlet conduit 24 may protrude through the skin of a subject and connect with the inlet of the lymph reservoir 12 that is external to the subject. The outlet 18 may be associated with a conduit 26, for example the outlet conduit 26 that penetrates the skin of a subject to allow return of the lymph to the vessel.

[084] With reference to Figure 1 , in one embodiment the access fitting 16 may be a self-sealing penetrable membrane such as a septum. The access fitting 16 may be a cap or lid, a fitting for a syringe such as a male or female luer lock fitting. For example the access fitting 16 may be associated with a further conduit (not shown). The further conduit may be configured to connect to a vessel at one end. The further conduit may be associated with a valve (not shown) such as an inflatable cuff. The valve 20 may seal the further conduit when not in use.

[085] The valve 20 or pressure release valve 22 may be a ball valve, a butterfly valve, a pinch valve, an inflatable cuff, a gate valve, a diaphragm valve, a needle valve, a check valve. Preferably the valve 20, or pressure release valve 22 is a unidirectional valve.

[086] In one embodiment the lymph reservoir 12 and/or the second reservoir 32 may include more than one chamber. Fpr example, and with reference to Figure 3, the lymph reservoir is divided into compartments 28 by at least one valve, or at least partition, baffle, support structure 30, or any combination thereof. [087] The inlet conduit 14 is configured to connect to a lymph duct by any suitable means known in the art. In one embodiment, the inlet conduit 14 is configured to connect to a lymph duct by anastomosis with the duct, catheterisation of the duct, or insertion into the duct. Typically this connection is made surgically.

[088] The outlet conduit 18 and/or the further conduit (not shown) may be configured to connect to a vessel by any suitable means known in the art. In one embodiment, the outlet conduit 18 and/or further conduit is adapted to be connected to a vessel for example by an anastomosis with the vessel, catheterisation of the vessel or insertion into the vessel. Typically this connection would also be made surgically.

[089] The outlet conduit 18 and/or the further conduit (not shown) may be connected with any vessel. In one embodiment the vessel may be a lymph duct, vein or ureter.

[090] In one embodiment the inlet conduit 14 may be connected to a stent (not shown) configured for placement within a lymph duct. In one embodiment, the outlet conduit 24 may be connected to the stent (not shown) or to another stent (not shown) configured for placement within a lymph duct or other vessel.

[091] In one embodiment the lymphatic access system 10 shown in Figure 4, in operation, is connected to a lymphatic duct such as the thoracic duct. In this

embodiment, the inlet 14 connects the thoracic duct to the lymph reservoir 12. A connecting conduit 38 connects the lymph reservoir and a second reservoir 32. The second reservoir 32 is connected with the thoracic duct by an outlet 18.

[092] Flow of lymph between the lymph reservoir 12 and the second reservoir 32, is controlled by a valve 40. In this embodiment, the valve 40 is associated with the connecting conduit 34 which provides fluid communication between the lymph reservoir 12 and the second reservoir 32.

[093] With reference to Figure 1 , an optional feature of the lymphatic access system 10 is a valve 20 associated with either or both of the inlet conduit 24 and the outlet conduit 26 and is located proximal to the thoracic duct. The valve 20 is configured to isolate the lymphatic access system 10 from the thoracic duct, for example when the lymphatic access system 10 is not in use.

[094] In another embodiment the lymphatic access system 10 as shown in Figure 4, in operation, is connected to a lymphatic duct, such as the thoracic duct and the left subclavian vein. In this embodiment the inlet 14 connects the thoracic duct to the lymph reservoir 12. A connecting conduit 34 connects the lymph reservoir 12 and a second reservoir 32. The second reservoir 32 is connected with the left subclavian vein by an outlet 18.

[095] Flow of lymph between the lymph reservoir 12 and the second reservoir 32 is controlled by a valve 40. In this embodiment, the valve 40 is associated with the connecting conduit 34, which provides fluid communication between the lymph reservoir 12 and the second reservoir 32.

[096] With reference to Figure 1 , an optional feature of the lymphatic access system 10 is a pressure release valve 22, illustrated as associated with the outlet conduit 26 and is located proximal to the thoracic duct. The pressure release valve 22 is configured to release lymph from the lymphatic access system 10 once a predetermined pressure is reached in the reservoir 12.

[097] With reference to Figure 5, the inlet conduit 24 and the outlet conduit 26 may be a multiple lumen catheter 48 inserted into the thoracic duct via percutaneous and transvenous techniques with entry for example from the left subclavian vein and held in place using an inflatable balloon 50 around the catheter.

[098] In an alternate embodiment illustrated in Figure 5 the lymphatic access system 10 may include a biocompatible, double lumen, balloon catheter 48 that may be delivered into the lumen of a major lymphatic trunk by percutaneous, transvenous techniques. The catheter 48 obviates the need for transmural connection. It provides an afferent conduit via lumen and an efferent conduit via lumen. The direction of flow of lymph may be controlled by inflation or deflation of inflatable balloon 50 which may be a lumen-occluding balloon. When the accessing component of the system is no longer required, this catheter 48 may be withdrawn by means of deflation of inflatable balloon 50. The catheter 48 may be introduced into the lumen of a lymphatic trunk via percutaneous, transvenous techniques known in the art.

[099] The present invention also relates to various uses of a system for accessing and processing lymph. For example, the lymphatic access system 10 is configured to direct lymph from a lymph vessel in a subject in a controlled fashion to allow acquisition and processing of the lymph with the option of returning some or all of the processed lymph to the subject. The lymphatic access system 10 may optionally include apparatus to process the lymph for therapeutic and/or diagnostic purposes. Any or all of the components comprising the system may be implantable and interchangeable.

[0100] Optional processing apparatus can include means to process the lymph for therapeutic purposes for example to remove lipids or metastatic cells or to isolate fractions of lymph or populations of cells in the lymph. In some embodiments the lymphatic access system 10 may be positioned external to a subject. Alternatively, the lymphatic access system 10 may be located subcutaneously for percutaneous use. That is, any or all of the components comprising the system may be implantable and interchangeable.

[0101] In one embodiment use of the lymphatic access system 10 may include processing to remove lipid from chylous lymph. The lipid-treatment can be configured to remove dietary lipid in the form of chylomicrons from chylous lymph. Beads coated with lipid-removing material(s) can be used and include for example anti-apo B antibodies, dextran sulphate cellulose, polyacrylate or other substances known in the art to be suitable for binding lipid. The beads coated with lipid removing materials can be capable of regeneration by the introduction of an eluting solution or solutions.

[0102] In another embodiment the lymphatic access system 10 may can be used to acquire lymphocytes, chylomicrons from chylous lymph or the incorporation of substances including drugs, biological agents (such as antibodies) or genetic materials for site-specific delivery. Use of the lymphatic access system 10 to acquire lymphocytes or chylomicrons as the acquisition of endogenous chylomicrons or lymphocytes will provide a substrate for incorporation of drugs, genetic material, biological agents such as antibodies, oligonucleotides and other therapeutic agents. The therapeutically modified lymphocytes and/or chylomicrons can then be re-introduced to a subject with the expectation that, in the case of modified chylomicrons, they will selectively be taken up by the liver. The use of endogenous lipoproteins and/or lymphocytes should prevent the development of an immune response against the vehicle carrying the therapeutic agent. This will permit the repeated administration of the agent concerned.

[0103] In another embodiment, the lymphatic access system 10 may can be used to retain and process the lymphocytes that are present within lymph fluid. In use, this enables the lymphatic fluid to be filtered so that lymphocytes are retained temporarily for purposes including incubation with therapeutic agents such as antibodies or

pharmaceutical agents.

[0104] In another embodiment use of the lymphatic access system 10 may include removing excess fluid and noxious substances in order to alleviate organ insufficiency such as liver failure, renal failure and cardiac failure. In this embodiment the lymphatic fluid collected by the lymphatic access system 10 can be filtered so that fluid and low molecular weight toxins are eliminated whilst lymphocytes and proteins are retained and continually or episodically returned to the circulation in order to maintain nutrition and immune sufficiency.

[0105] In a further embodiment the lymphatic access system 10 can be used to remove noxious substances which contribute to shock, adult respiratory distress syndrome sepsis and severe illness. In this embodiment the lymphatic access system 10 enables the lymphatic fluid in the system to be eliminated or processed to selectively retain favourable elements. This lymphatic access system may also be applied to the management of severe food allergies. In the context of serious food allergy the allergenic dietary proteins are retained by the apparatus and prevented from reaching the systemic circulation.

[0106] Appropriate isolation of fluids can be maintained by appropriately incorporated one-way valves, taps, and flow control devices. The valves, taps and flow control devices may be activated remotely, including external activation of internally implanted valves, taps and flow control devices. The control of flow prevents mixing of inwardly (unprocessed) and outwardly flowing (processed) lymph.

[0107] The lymphatic access system 10 can be used for the acquisition of lymph and/or lymph components for diagnostic pathology testing by means of biochemical, serological, microbiological, genetic, cytological, immunological, histopathological, flow cytometry or other methods known in the art. The sample for analysis may be acquired by percutaneous insertion of a needle and aspiration of the sample from the lymph reservoir 12. In some embodiments, the lymphatic access system 10 is connected to the thoracic duct, which drains all regions except for the right arm, shoulder, neck and head. Therefore the lymph from the thoracic duct can be used to monitor the status of all other regions of the body for signs of pathology, particularly metastasis of malignancies. Monitoring of regions that are not drained by the thoracic duct may be undertaken by connection of the lymphatic access system 10 to another major lymph trunk.

[0108] In some embodiments the second reservoir 32 or compartment 28 may contain, for example, affinity beads which may sequester malignant cells (or other targets), and which may provide samples of those beads for analysis or treatment. The analysis may be designed to detect the presence of bead-bound malignant cells (or other targets) and thereby identify the possibility of metastasis (or other pathological processes) and the need for treatment of the source.

[0109] The present invention provides a lymphatic access system 10 which can divert lymph flow and allow access to the lymph. Additionally, in some embodiments a dual reservoir of the lymphatic access system 10 is particularly suitable for procedures requiring simultaneous inflow and outflow of lymph.

[0110] Although the illustrative embodiments of the present invention have been described with reference to the accompanying drawings, it is to be understood that the invention is not limited to those precise embodiments, and that various other changes and/or modifications may be made by one skilled in the art without departing from the scope or spirit of the invention.

Cross Reference to Related Application

[0111] This application claims priority to US provisional patent application

No 61/675,177 filed 24 July 2012 which is herein incorporated by reference in its entirety.

Claims

Claims:

1. A lymphatic access system comprising:

an inlet configured to divert lymph from a lymph duct in a subject to the lymph reservoir; an outlet configured to allow lymph in the lymph reservoir to return to a vessel in the subject; and

2. The lymphatic access system of claim 1 comprising an access fitting associated with the lymph reservoir to allow access to^' lymph in the lymph reservoir.

3. The lymphatic access system of claim 1 or 2 comprising a pressure release valve.

4. The lymphatic access system of any one of claims 1 to 3 wherein the inlet includes an inlet conduit configured to connect to a lymph duct of a subject at one end and divert lymph from the lymph duct of the subject to the lymph reservoir.

5. The lymphatic access system of claim 4 wherein the inlet conduit is configured to connect to a lymph duct by anastomosis with the duct, catheterisation of the duct, or insertion into the duct.

6. The lymphatic access system of any one of claims 1 to 4 wherein the outlet includes an outlet conduit configured to connect to a vessel of a subject at one end and allow lymph from the lymph reservoir to return to a vessel of the subject.

7. The lymphatic access system of claim 6 wherein the outlet conduit is adapted to be connected to a vessel by an anastomosis with the vessel, catheterisation of the vessel or insertion into the vessel.

8. The lymphatic access system of any one of claims 1 to 7 wherein the vessel is a lymph duct, vein or ureter.

9. The lymphatic access system of any one of claims 1 to 8 wherein the lymph reservoir has two or more compartments capable of receiving lymph.

10. The lymphatic access system of any one df claims 1 to 9 comprising a second reservoir in fluid communication with the lymph reservoir.

11. The lymphatic access system of claim 10 wherein the second reservoir is configured to allow access to lymph in the second reservoir.

12. The lymphatic access system of claim 10 or 11 wherein the second reservoir includes:

an inlet configured to receive lymph from the lymph reservoir; and

an outlet configured to allow lymph to be removed from the second reservoir.

13. The lymphatic access system of any one of claims 10 to 12 wherein the outlet includes a conduit configured to connect to a vessel of a subject at one end and allow lymph from the second reservoir to return to a vessel of the subject.

14. The lymphatic access system of any one of claims 10 to 12 wherein the second reservoir includes an access fitting configured to allow access to lymph in the second reservoir.

15. The lymphatic access system of any one of claims 10 to 14 wherein the second reservoir includes a valve configured to control flow of lymph to or from the second reservoir.

16. The lymphatic access system of any one of claims 1 to 15 being implantable in a subject.

17. The lymphatic access system of claim 16 configured for subcutaneous implantation in a subject.

18. The lymphatic access system of any one of claims 1 to 17 wherein the subject is a mammal.

19. The lymphatic access system of claim 18, wherein the mammal is a human, sheep, pig, rabbit or rat.

20. The lymphatic access system of any one of claims 1 to 16 wherein access to lymph in the lymph reservoir is through an access fitting, self-sealing membrane, cap, lid, or a fitting for a syringe.

21. A kit comprising:

a lymphatic access system according to any one of claims 1 to 20; and at least one catheter configured to provide fluid communication between a lymph duct in a subject and the lymph reservoir of the lymphatic access system.

22. A method for diverting lymph from a subject, the method comprising: connecting a lymphatic access system according to any one of claims 1 to 20 to a lymph duct of a subject; and

accessing lymph in the lymph reservoir; and

returning to a vessel in the subject.

23. The method of claim 22 wherein the lymph accessed from the lymph reservoir is separated, fractionated, refined, or purified.

24. The method of claim 23 wherein the accessed lymph is altered by

pharmacological, biochemical, physical or molecular means.

25. The method of claim 24 wherein the pharmacological alteration includes drug treatment, immuno-therapy, or transfection of a biological material.

26. The method of any one of claims 22 to 25 wherein the lymph within the lymph reservoir is diverted in response to a pathological disease or condition.

27. The method according to claim 26 wherein the pathological disease or condition is selected from the group consisting of cardiovascular disease, hyperlipidaemia, diabetes, infectious disease, obesity, metabolic syndrome associated with obesity, organ failure, autoimmune disease, transplant rejection, malignancies including de novo or recurrent malignancies, neurodegenerative diseases, organ failure, sepsis, shock lung, and food allergies.

28. The method of claim 27 wherein the neurodegenerative disease is Alzheimer's disease.

29. The method of claim 27 wherein organ failure is kidney failure, cardiac failure or liver failure.