Minimally-invasive CLOG-resistant shunts and catheters

Abstract

Described herein are fluid management devices (FMDs), including shunts and catheters, that can exhibit improved clog resistance and reduce surgical risk. The FMDs described herein can include a durable, extremely slippery, hydrophobic coating that reduces the ability of biological matter to stick to the device surface and reduces drag for fluid flow. Thus, the FMDs described herein can be particularly well suited for drainage of sticky bodily fluids, such as CSF, that are prone to clogging traditional FMDs. The FMDs described herein can, in some embodiments, possess a reduced inner diameter compared to traditional FMDs due to the lower incidence of clogging. The reduction in clogging in FMDs may also increase the lifetime of the devices in vivo.

Description

MINIMALLY-INVASIVE CLOG-RESISTANT SHUNTS AND CATHETERSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to, and the benefit of, U.S. Provisional Application No. 63 / 518,446 filed on August 9, 2023, the disclosure of which is hereby expressly incorporated by reference herein in its entirety.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to medical devices for the management and manipulation of bodily fluids within living organisms. More specifically, the present disclosure relates to such medical devices, such as shunt or catheter devices, that can be prone to clogging once deployed in vivo.BACKGROUND

[0003] Any discussion of the related art throughout this specification should in no way be considered as an admission that such art is widely known or forms part of the common general knowledge of the field.

[0004] There are a wide variety of fluids within most living organisms, such as humans, that are critical to bodily operation. Abnormalities in the properties and distribution of these fluids are associated with a range of physiological and neurological conditions, including hydrocephalus, ascites, pleural effusion, idiopathic intracranial hypertension (IIH), and biliary duct obstruction. Treatment of these conditions often involves surgical intervention to restore proper fluid levels and distribution through the introduction of a shunt, catheter, or similar device, hereafter referred to as a fluid management device (FMD), to redirect fluid within the body, or to add or remove fluid from the body.

[0005] Hydrocephalus is a common application of FMDs, and results from the abnormal buildup of cerebrospinal fluid (CSF) in the ventricles deep within the brain. Elevated CSF volume within the ventricles exerts pressure on the surrounding brain tissues, causing a variety of neurological symptoms. In general, hydrocephalus can be either communicating, in which CSF throughout the brain, subarachnoid spaces, and spinal cord is at approximately equal pressure, or non-communicating, where an occlusion within the brain causes the development of isolated regions of elevated pressure. Approximately 20% of hydrocephalus cases are noncommunicating, for which there are few treatment options that do not require neurosurgery.

[0006] Communicating hydrocephalus is often treated through the installment of a shunt or catheter to drain CSF from areas of the central nervous system (CNS), including the brain ventricles or thecal sac, and into other regions of the body such as the peritoneum, third ventriculostomies, or subcutaneous tissue. Standard treatments include ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts, which drain from the ventricles to the peritoneal cavity or right atrium of the heart, respectively, and lumbar shunts, which access CSF in the thecal sac through the lumbar portion of the spinal cord and drain either externally, subcutaneously or into the peritoneal cavity.

[0007] Currently, all the standard treatments for hydrocephalus are surgical procedures, and VP and VA shunts in particular require extensive neurosurgery to route fluids from deep within the brain. Despite the relatively higher surgical risk, VP and VA shunts have a well- established clinical efficacy in managing chronic hydrocephalus and are the current standard-of- care, except in cases in which VA or VP shunts are deemed ineligible. This can be due to complications such as the development of slit ventricles due to chronic CSF shunting [Maripudi 2018]. Lumbar shunts, on the other hand, provide less invasive access to the CSF but are thought to be prone to clogging, overdrainage, or the development of Chiari malformation.

[0008] Subcutaneous lumbar (LS) shunts are a particularly attractive alternative to VP, VA, lumboperitoneal (LP), and externally draining lumbar (LE) shunts, owing to their minimally invasive installation that avoids neurosurgery and their ease of access for sampling. Currently, LS shunt installment is still a surgical procedure, and there is considerable interest in developing an LS shunt that can be installed in a bedside operation. Treatment of hydrocephalus with LS shunts has been shown to provide relief for some patients over a period of 1-6 months [Ushewokunze 2008]. Without being bound by theory, reducing the incidence of clogging may enable longer term employment of LS shunts to manage hydrocephalus. Traditionally, the risk of clogging has been mitigated by increasing the inner diameter of the shunt, with a current minimum diameter of roughly 1.5 mm.

[0009] Installment of any FMD often requires surgical procedures with varying degrees of risk and invasiveness which can influence patient outcomes. In some cases, the installation may be deemed too dangerous or difficult, potentially resulting in progression of the condition. Some patients with hydrocephalus, for instance, may be deemed ineligible for standard surgical intervention and go on to develop complications such as dementia. Patients that are treated with FMDs can face risks associated with device failure, over or underdrainage, and infection, all of which can lead to ineffective treatment or potentially life-threatening emergencies.

[0010] There is therefore a considerable interest in the development of new FMDs with decreased surgical risk and complexity. To this end, the present disclosure discusses FMDs with increased clog resistance, which enables the use of smaller FMDs and opens new treatment pathways with lower risk.

[0011] The compositions disclosed herein address these and other needs.SUMMARY OF THE DISCLOSURE

[0012] The present disclosure relates generally to shunts, catheters, and similar devices, referred to as fluid management devices (FMDs), with improved clog resistance and reduced surgical risk. The FMDs of the present disclosure, hereafter referred to as clog-resistant FMDs (CFMDs), possess a durable, extremely slippery, hydrophobic coating that reduces the ability of biological matter to stick to the device surface and reduces drag for fluid flow. The CFMDs of the present disclosure are ideally suited for drainage of sticky bodily fluids, such as CSF, that are prone to clogging traditional FMDs. The CFMDs described herein can possess a reduced inner diameter compared to traditional FMDs due to the lower incidence of clogging. The reduction in clogging in CFMDs may increase lifetime of the devices. To this end, the present disclosure describes CFMDs and specific applications thereof.

[0013] According to one aspect of the present disclosure, a CFMD comprises a tube that enables fluid drainage from one location within the body to another, wherein at least some of the tube has a clog-resistant coating that permits the use of a narrow inner diameter.

[0014] According to one aspect of the present disclosure, the clog-resistant coating is superhydrophobic.

[0015] According to one aspect of the present disclosure, the clog-resistant coating comprises a fluorinated polymer surface covered with a fluorinated liquid.

[0016] According to one aspect of the present disclosure, the CFMD drains liquid from a source or reservoir of bodily fluid.

[0017] According to one aspect of the present disclosure, the CFMD drains liquid to the resorption location within the body.

[0018] According to one aspect of the present disclosure, the CFMD drains liquid to the subcutaneous tissue.

[0019] According to one aspect of the present disclosure, the CFMD extends into a source or reservoir of bodily fluid.

[0020] According to one aspect of the present disclosure, the CFMD comprises one or more flow restrictors.

[0021] According to one aspect of the present disclosure, the CFMD comprises one or more fluid reservoirs.

[0022] According to one aspect of the present disclosure, the CFMD has a desired shape.

[0023] According to one aspect of the present disclosure, the CFMD comprises multiple drainage pathways.

[0024] According to one aspect of the present disclosure, the CFMD drains fluid to multiple subcutaneous tissue regions.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects described below.

[0026] FIG. 1 A provides a diagram of the central nervous system in a human, showing the location of cerebrospinal fluid.

[0027] FIG. IB illustrates the treatment of hydrocephalus with a ventriculoperitoneal shunt.

[0028] FIG. 1C illustrates the treatment of hydrocephalus with a ventriculoatrial shunt.

[0029] FIG. ID illustrates the treatment of hydrocephalus with a lumboperitoneal shunt.

[0030] FIG. 1 E illustrates the treatment of hydrocephalus with a subcutaneous lumbar shunt.

[0031] FIG. 2A provides a cut-away view of a tube within a fluid management device with a clog-resistant coating on the inner surface.

[0032] FIG. 2B provides a cross-sectional view of a tube within a fluid management device with a clog-resistant coating on the inner surface.

[0033] FIG. 3A provides a cut-away view of a tube within a fluid management device with a clog-resistant coating on the outer surface.

[0034] FIG. 3B provides a cross-sectional view of a tube within a fluid management device with a clog-resistant coating on the outer surface.

[0035] FIG. 4A provides a cut-away view of a tube within a fluid management device with a clog-resistant coating on both the inner and outer surfaces.

[0036] FIG. 4B provides a cross-sectional view of a tube within a fluid management device with a clog-resistant coating on both the inner and outer surfaces.

[0037] FIG. 5A is a diagram of a clog-resistant fluid management device for subcutaneous fluid drainage with a single drainage pathway.

[0038] FIG. 5B illustrates the treatment of hydrocephalus with the subcutaneous clogresistant fluid management device of FIG. 5 A.

[0039] FIG. 6A is a diagram of a clog-resistant fluid management device for subcutaneous fluid drainage with multiple drainage pathways.

[0040] FIG. 6B illustrates the treatment of hydrocephalus with the subcutaneous clog- resistant fluid management device of FIG. 6A.

[0041] FIG. 7A is a diagram of a clog-resistant fluid management device for subcutaneous fluid drainage with an attached fluid reservoir.

[0042] FIG. 7B illustrates the treatment of hydrocephalus with the subcutaneous clog- resistant fluid management device of FIG. 7A.

[0043] FIG. 8 is a diagram of a clog-resistant fluid management device with an attached flow restrictor.

[0044] FIG. 9 is a diagram of a clog-resistant fluid management device with a tapered end.DETAILED DESCRIPTION

[0045] The following description of the disclosure is provided as an enabling teaching of the disclosure in its best, currently known embodiments. Many modifications and other embodiments disclosed herein will come to mind to one skilled in the art to which the disclosed compositions and methods pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the disclosures are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein.

[0046] Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0047] As can be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure.

[0048] Any recited method can be carried out in the order of events recited or in any other order that is logically possible. That is, unless otherwise expressly stated, it is in no wayintended that any method or aspect set forth herein he construed as requiring that its steps he performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

[0049] All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation.

[0050] It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods belong. It can be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly defined herein.

[0051] Prior to describing the various aspects of the present disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in the present disclosure.Definitions

[0052] As used herein, “comprising” is to be interpreted as specifying the presence of the stated features, integers, steps, or components as referred to, but does not preclude the presence or addition of one or more features, integers, steps, or components, or groups thereof. Moreover, each of the terms “by”, “comprising,” “comprises”, “comprised of,” “including,” “includes,” “included,” “involving,” “involves,” “involved,” and “such as” are used in their open, nonlimiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms “consisting essentially of’ and“consisting of.” Similarly, the term “consisting essentially of’ is intended to include examples encompassed by the term “consisting of.”

[0053] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound”, “a composition”, or “a disorder”, includes, but is not limited to, two or more such compounds, compositions, or disorders, and the like.

[0054] It should be noted that ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. It can be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it can be understood that the particular value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed.

[0055] When a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g., the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’ . The range can also be expressed as an upper limit, e.g., ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of Tess than x’, less than y’, and Tess than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’, greater than y’, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’”.

[0056] It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g.,about 0.5% to about 1.1 %; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range.

[0057] As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “substantially free,” when used in the context of a composition or component of a composition that is substantially absent, is intended to refer to an amount that is then about 1 % by weight or less, e.g., less than about 0.5 % by weight, less than about 0.1 % by weight, less than about 0.05 % by weight, or less than about 0.01 % by weight of the stated material, based on the total weight of the composition.Product

[0058] Provided herein is a clog-resistant fluid management device, the device comprising: a tube body comprising a distal tip and at least one drainage tip, an inner surface; and an outer surface; wherein the distal tip facilitates fluid flow between the tube body and a first location within a living organism, wherein the drainage tip facilitates fluid flow between the tube body and at least one second location within a living organism, wherein at least one portion of the inner surface, the outer surface, the distal tip, the drainage tip, or a combination thereof, comprises a clog-resistant coating, and wherein said tube body has an inner diameter of from greater than 0 mm to 5 mm.

[0059] A living organism refers to anything that has life and is made up of cells as its basic unit of organization. More specifically, living organism includes subjects such as humans and animals.

[0060] In some embodiments, the tube body can have an inner diameter of 5 mm or less (e.g., 4.75 mm or less, 4.5 mm or less, 4.25 mm or less, 4 mm or less, 3.75 mm or less, 3.5 mm or less, 3.25 mm or less, 3 mm or less, 2.75 mm or less, 2.5 mm or less, 2.25 mm or less, 2 mm or less, 1.9 mm or less, 1.8 mm or less, 1.7 mm or less, 1.6 mm or less, 1.5 mm or less, 1.4 mm or less, 1.3 mm or less, 1.2 mm or less, 1.1 mm or less, 1 mm or less, 0.9 mm or less, 0.8 mm or less, 0.7 mm or less, 0.6 mm or less, 0.5 mm or less, 0.4 mm or less, 0.3 mm or less, 0.2 mm or less, or 0.1 mm or less). In some embodiments, the tube body can have an inner diameter greater than 0.0 mm (e.g., at least 0.1 mm, at least 0.2 mm, at least 0.3 mm, at least 0.4 mm, at least 0.5 mm, at least 0.6 mm, at least 0.7 mm, at least 0.8 mm, at least 0.9 mm, at least 1 mm, at least 1.1 mm, at least 1 .2 mm, at least 1 .3 mm, at least 1 .4 mm, at least 1 .5 mm, at least 1 .6 mm, at least 1.7 mm, at least 1.8 mm, at least 1.9 mm, at least 2 mm, at least 2.25 mm, at least 2.5 mm, at least 2.75 mm, at least 3 mm, at least 3.25 mm, at least 3.5 mm, at least 3.75 mm, at least 4 mm, at least 4.25 mm, at least 4.5 mm, or at least 4.75 mm).

[0061] The tube body can have an inner diameter ranging from any of the minimum values described above to any of the maximum values described above. In some examples, the tube body can have an inner diameter of from greater than 0 mm to 5 mm (e.g., from greater than 0 mm to 4 mm, from greater than 0 mm to 3 mm, from greater than 0 mm to 2 mm, or from greater than 0 mm to 1 mm). In further examples, tube body can have an inner diameter of from 1 to 2 mm, from 2 to 3 mm, 3 to 4 mm, or 4 to 5 mm. In further examples, the tube body can have an inner diameter of from 2 to 2.5 mm, 2.5 to 3 mm, 3 to 3.5 mm, 3.5 to 4 mm, 4 to 4.5 mm, or 4.5 to 5 mm. In certain examples, said tube body has an inner diameter of from 2 to 3.5 mm, 2 to 4 mm, or 2 to 4.5 mm. In specific examples, said tube body has an inner diameter of from 2 to 2.25 mm, 2.25 to 2.5 mm, 2.5 to 2.75 mm, 2.75 to 3 mm, 3 to 3.25 mm, 3.25 to 3.5 mm, 3.5 to 3.75 mm, 3.75 to 4 mm, 4 to 4.25 mm, 4.25 to 4.5 mm, 4.5 to 4.75 mm, or 4.75 to 5 mm. In some examples, said tube body has an inner diameter of from 2 to 2.75 mm, 2 to 3.25 mm, 2 to 3.75 mm, 2 to 4.25 mm, or 2 to 4.75 mm.

[0062] In further examples, the inner diameter is 1 mm or less, 0.9 mm or less, 0.8 mm or less, 0.7 mm or less, 0.6 mm or less, 0.5 mm or less, 0.4 mm or less, 0.3 mm or less, 0.2 mm or less, 0.1 mm or less, or between 0 mm and 1 mm.

[0063] In some examples, said clog-resistant coating is hydrophobic or superhydrophobic.

[0064] Hydrophobic refers to surfaces that allow water droplets to roll off due to the surface having a static water contact angle greater than 90°.

[0065] Superhydrophobic refers to surfaces with high water contact angles and low surface energy, thereby allowing water droplets to roll off easily due to lower contact angle hysteresis. More specifically, superhydrophobic surfaces have a static water contact angle of greater than 150°.

[0066] In further examples, the clog-resistant coating is durable. Durable is used to refer to a material able to withstand wear, pressure, or damage, particularly when used inside the living organism.

[0067] In certain examples, the clog-resistant coating is slippery. Slippery is used to refer to a surface with a low coefficient of friction, thereby allowing objects to glide across the surface, particularly biological materials such as blood.

[0068] In specific examples, the clog-resistant coating comprises a fluorinated surface covered with a fluorinated liquid.

[0069] A fluorinated surface is a surface exposed to fluorine, which due to its high reactivity, partially replaces hydrogen atoms on the material’s surface.

[0070] A fluorinated liquid is a liquid with certain properties that result from the presence of fluorine atoms in their chemical structure.

[0071] In some examples, the fluorinated surface comprises fluoropolymers or perfluoropolymers selected from the group consisting of: perfluoroalkoxy alkanes; polytetrafluoroethylene; fluorinated ethylene propylene; expanded polytetrafluoroethylene; expanded fluorinated ethylene propylene; perfluoromethylvinylether; perfluoro elastomers; ethylene tetrafluoroethylene; polyvinylidene fluoride; fluoroelastomers; vinylidene fluoridehexafluoropropylene fluoroelastomer; vinylidene fluoride-hexafluoropropylene / tetrafluoro ethylene / hexafluoropropylene fluoroelastomer terpolymer; and combinations thereof.

[0072] In further examples, the fluorinated surface comprises polytetrafluoroethylene.

[0073] Fluoropolymer refers to fluorocarbon-based polymers with multiple carbonfluorine bonds. In some examples, fluorocarbons are not as susceptible to van der Waals force as hydrocarbons, thereby resulting in their non-stick and friction reducing properties. In further examples, fluoropolymers have increased stability due to the carbon-fluorine bonds in the chemical structure. Fluoropolymers can include thermosets and thermoplastics. Further, fluoropolymers can be homopolymers or copolymers.

[0074] Perfluoropolymers are a type of fluoropolymer in which the hydrogens bonded to carbon in the chemical structure are replaced by fluorine atoms. This is in contrast to other fluoropolymers which are partially fluorinated.

[0075] In further examples, the fluorinated liquid includes one or more solvents selected from: perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluorooctane, perfluorodecalin, perfluoroperhydrophenanthrene, perfluorooctylbromide, perfluoro tributyl amine, perfluorotripentyl amine, poly(hexafluoropropylene oxide) and combinations thereof.

[0076] In some examples, the fluorinated liquid comprises perfluorodecalin.

[0077] Solvent refers to a substance capable of dissolving one or several substances.

[0078] In certain examples, the first location within a living organism is one of the thecal sac, the ventricles, the central nervous system, the chest cavity, or the biliary duct.

[0079] The thecal sac (also known as dural sac) is the membranous sheath or tube of dura mater that surrounds the spinal cord and the cauda equina. The thecal sac contains the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord. The thecal sac has projections that follow the spinal nerves along their paths out of the vertebral canal which become the dural root sheaths.

[0080] The central nervous system is a part of the nervous system and includes the brain and spinal cord. The central nervous system collects information from sensory nerves to process and respond to them, thereby regulating everything the body does.

[0081] The chest cavity, also known as the thoracic cavity, is a space in the chest that contains the heart, lungs, and other organs and tissues.

[0082] The biliary duct, also known as the common bile duct, is a tube that carries bile from the liver and gallbladder through the pancreas and into the small intestine. It starts where the ducts from the liver and gallbladder join and ends at the small intestine.

[0083] In specific examples, the at least one second location within a living organism is one or more of, or a combination of, a subcutaneous tissue region, peritoneum, pleural cavity, the heart (e.g., an atrium of the heart), or a vein.

[0084] The subcutaneous tissue region, also called the hypodermis, is a layer of connective tissue that lies immediately below the dermis and contains fat, larger blood vessels, and nerves.

[0085] The peritoneum is a membrane made of a sheet of smooth tissue that lines the abdominopelvic cavity and surrounds the abdominal organs. It pads and insulates the organs and helps hold them in place, secreting a lubricating fluid to reduce friction when they rub against each other.

[0086] The pleural cavity is a space between the visceral and parietal pleura, which are thin layers of tissue that surround the lungs and line the chest cavity.

[0087] A vein is a blood vessel located throughout the body that collects oxygen-poor blood and returns it to the heart.

[0088] In some examples, said subcutaneous tissue is located in one of the back, stomach, legs, pelvis, buttocks, chest, arms, neck, or cranium.

[0089] In further examples, the device extends from 1 cm to 15 cm into said first location within a living organism.

[0090] In some examples, the device extends from 1 to 2 cm, 2 to 3 cm, 3 to 4 cm, 4 to 5 cm, 5 to 6 cm, 6 to 7 cm, 7 to 8 cm, 8 to 9 cm, 9 to 10 cm, 10 to 11 cm, 11 to 12 cm, 12 to 13 cm, 13 to 14 cm, or 14 to 15 cm. In further examples, the device extends from 1 to 3 cm, 3 to 5 cm, 5 to 7 cm, 7 to 9 cm, 9 to 1 1 cm, 1 1 to 13 cm, or 13 to 15 cm. In certain examples, the device extends from 1 to 5 cm, 5 to 10 cm, or 10 to 15 cm. In specific extends from 1 to 4 cm, 1 to 5 cm, 1 to 6 cm, 1 to 7 cm, 1 to 8 cm, 1 to 9 cm, 1 to 10 cm, 1 to 11 cm, 1 to 12 cm, 1 to 13 cm, or 1 to 14 cm.

[0091] In certain examples, the device further comprises at least one flow restrictor.

[0092] A flow restrictor, also known as a flow limiter, is a device that restricts or limits the flow of a fluid.

[0093] In specific examples, the flow restrictor is one of a nozzle, valve, HV valve, bladder valve, or tapered segment.

[0094] In some examples, a nozzle refers to a pipe or tube of varying cross-sectional area and it can be used to direct or modify the flow of a fluid, such as the rate of flow, speed, direction, mass, shape and / or the flow pressure.

[0095] In further examples, a valve is a device that opens and closes to control the flow of fluids. In some examples, a valve closes temporarily a passage or orifice through which a fluid flow or permits movement of fluid in one direction only.

[0096] A bladder valve is a valve used to shut off, throttle, or dose materials, such as dose bulk solids, suspensions, sludge, fibrous or corrosive media, powders, granulates, and / or slurries. Bladder valves can be mechanical or pneumatic and can be controlled manually with a hand wheel or with accessories like solenoid valves, pressure regulators, and limit switches.

[0097] In some examples, at least one of the at least one flow restrictor is located at one of, or a combination of, the distal tip, drainage tip, or tube body.

[0098] In further examples, the device further comprises at least one fluid reservoir.

[0099] Fluid reservoir refers to a place in the device where fluid is held. In some examples, the fluid reservoir holds fluid collected from the living organism. In further examples, the fluid reservoir holds fluid administered to the living organism.[000100] In certain examples, at least one portion of the tube body has a predefined shape.[000101] As used herein, predefined shape refers to a defined structure with specific dimensions such as height, length, width, diameter, for example.[000102] In specific examples, the device comprises at least 1 drainage tip, wherein each of said drainage tips facilitates fluid flow to a different second location within said living organism. [000103] In some examples, the device comprises at least 1 drainage tip, at least 2 drainage tips, at least 3 drainage tips, at least 4 drainage tip, or at least 5 drainage tips.[000104] In some examples, each of said different secondary locations is a subcutaneous tissue region.[000105] The present disclosure introduces an effective means for fluid management within living organisms, including humans. Fluid management devices (FMDs), as defined herein, refer to shunts, catheters and similar devices that enable fluid flow from one part of the body to another, or into or out of a particular part of the body. FMDs are often used in the treatment of various diseases caused by abnormal fluid levels in the body, including hydrocephalus, ascites, pleural effusion, and idiopathic intracranial hypertension, among others. FMDs provide relief of abnormal fluid buildup by allowing drainage of fluids into another part of the body where it can be resorbed, or out of the body entirely into a collection system. FMDs can also provide access to bodily fluids for sampling or infusion through attached reservoirs or additional lumens.Clogging and infection are particularly salient for FMDs managing cerebrospinal fluid (CSF), owing to the high viscosity of CSF and the sensitive areas being drained. The present disclosure teaches methods to form clog-resistant FMDs (CFMDs) and methods of utilizing the same to form a subcutaneous lumbar shunt for CSF.[000106] The CFMDs of the present disclosure possess superior clog and infection resistance owing to their extremely slippery, hydrophobic coating. This permits the use of a smaller inner diameter and may enable less invasive treatment options for certain conditions in certain patients. In one example, the CFMDs of the present disclosure may be ideal for the treatment of hydrocephalus through a subcutaneous lumber shunt (LS). Hydrocephalus treatment requires drainage of CSF from regions of elevated pressure, which can be in either isolated pockets or throughout the entire central nervous system (CNS). As shown in FIGS. 1A-1E, CSF is located throughout the CNS 100 and can be accessed directly through the ventricles 101 or through the thecal sac 102 by FMDs including ventricular and lumbar shunts.[000107] FIG. 1B-1C depict a ventriculoperitoneal (VP) shunt 110 and a ventriculoatrial(VA) shunt 120 for treatment of communicating or non-communicating hydrocephalus. VP shunt 110 drains CSF from the ventricles 101 into the peritoneal cavity 103 in the abdomen, while VAshunt 120 drains from the ventricles 101 into the right atrium of the heart 104. Other ventricular shunt options include ventriculopleural shunts and ventriculovenous shunts, among others. Installment of ventricular shunts requires neurosurgery to access the ventricles and route CSF across the body. Despite the requirement for neurosurgery, ventricular shunts are often the standard of treatment, as they are thought to exhibit lower incidence of clogging. Chronic use of ventricular shunts, however, can lead to the development of slit ventricles, particularly in infants and children, which can prevent further use of ventricular shunts [Marupudi 2018].[000108] FIG. ID depicts a lumboperitoneal (LP) shunt 130 for communicating hydrocephalus treatment. Instead of accessing the ventricles directly, LP shunt 130 drains CSF from the thecal sac 102 into the peritoneum 103. While installment of LP shunt 130 does not require surgery to access the thecal sac, routing the shunt from the spine into the peritoneum is a surgical procedure. LP shunts are a second standard treatment for hydrocephalus and have demonstrated success at managing cases that cannot be treated with ventricular shunts. LP shunts, however, are thought to be prone to clogging and overdrainage, and may pose challenges for accessing CSF for sampling.[000109] FIG. IE depicts a subcutaneous lumbar (LS) shunt 140 for communicating hydrocephalus treatment. LS shunt 140 drains CSF from the thecal sac 102 into subcutaneous tissues which can be located in various positions within the body, including in the back, stomach, legs, arms, pelvis, buttocks, chest or neck. While installment of LS shunt 140 does not require surgery to access the thecal sac, routing the shunt from the spine into the subcutaneous tissues may or may not be a surgical procedure, depending on the position within the body. The significantly reduced invasiveness of the LS shunt may be ideal for managing certain types of hydrocephalus in some individuals.[000110] In a first aspect of the present disclosure, a CFMD comprises a hollow tube with a clog-resistant coating on the inner surface of the tube. FIGS. 1A and IB provide cut-away and cross-sectional views of CFMD 100 according to the present disclosure. CFMD 100 comprises a hollow tube body 110 with a clog-resistant coating 120 formed on the inner surface of tube body 110. As defined herein, a clog-resistant coating is hydrophobic or superhydrophobic, durable and extremely slippery. As defined herein, an extremely slippery coating has a coefficient of static friction of between 0.01 and 0.1 and substantially inhibits cellular adhesion. As defined herein, a durable coating is substantially resistant to degradation within a biological environment. Clog- resistant coating 120 reduces fluid flow resistance and inhibits the adhesion of biological matter to the inner surface of the tube. Without being bound by theory, the reduction in adhesion of biological matter to the inner surface of the CFMD reduces the incidence of clogging andinfection. Reduction in the incidence of clogging enables the use of a narrow inner diameter, which lowers surgical risk and invasiveness, and may be more comfortable for the patient.[000111] In another aspect of the present disclosure, a CFMD comprises a hollow tube with a clog -resistant coating on the outer surface of the tube. FIGS. 2A and 2B provide cut-away and cross-sectional views of CFMD 200 according to the present disclosure. CFMD 200 comprises a hollow tube body 210 with a clog-resistant coating 230 formed on the outer surface of tube body 210. Clog-resistant coating 230 is hydrophobic or superhydrophobic, durable and extremely slippery. Clog-resistant coating 230 reduces the adhesion of biological matter to the outer surface of the tube. Without being bound by theory, reducing the adhesion of biological matter to the outer surface of the CFMD reduces the incidence of clogging and infection. Reduction in the incidence of clogging enables a narrow inner diameter, which lowers surgical risk and invasiveness, and may be more comfortable for the patient.[000112] In a third aspect of the present disclosure, a CFMD comprises a hollow tube with a clog-resistant coating on both the inner and outer surface of the tube. FIGS. 3A and 3B provide cut-away and cross-sectional views of CFMD 300 according to the present disclosure. CFMD 300 comprises a hollow tube body 310 with clog-resistant coatings 320 and 330 formed on the inner and outer surfaces of tube body 210, respectively. Clog-resistant coatings 320 and 330 reduce the adhesion of biological matter to the surfaces of tube 310. Without being bound by theory, the reduction in adhesion of biological matter to the surfaces of the CFMD reduces the incidence of clogging and infection. Reduction in the incidence of clogging enables a narrow inner diameter, which lowers surgical risk and invasiveness, and may be more comfortable for the patient.[000113] In some examples, the hollow tube bodies 110, 210 and 310 have a narrow inner diameter of less than 2 mm or less than 1 mm or less than 0.9 mm or less than 0.8 mm or less than 0.7 mm or less than 0.5 mm or less than 0.4 mm or less than 0.3 mm or less than 0.2 mm or less than 0.1 mm. The diameter of hollow tube bodies 110, 210 and 310 can be substantially narrow due to the presence of clog-resistant coatings 120, 230, 320, and 330. Without these coatings, hollow tube bodies 110, 210 and 310 may experience high degrees of clogging, a short usable lifespan, and insufficient flow rate. In some aspects of the present disclosure, the diameter of the CFMD used in the treatment of an individual may be chosen to achieve a particular flow rate. In some examples, the flow rate through tube bodies 110, 210 or 310 is between 0 and 100 mL / min, or 100 and 200 mL / min, or 200 and 300 mL / min, or 300 and 400 mL / min, or 400 and 500 mL / min, or 500 and 1000 mL / min, or 1000 and 1500 mL / min, or greater than 500 mL / min.[000114] In some aspects of the present disclosure, the clog -resistant coating is hydrophobic, with a static water contact angle of between roughly 90° and roughly 170°. In some aspects of the present disclosure, the clog-resistant coating is superhydrophobic, with a static water contact angle of greater than roughly 170°. In some aspects of the present disclosure, the clog-resistant coating is provided by a tethered-liquid perfluorocarbon (TLP) coating according to the methods of U.S. Patent No. 9,932,484, which are incorporated herein by reference. TLP coatings have been shown to exhibit hydrophobicity and prevent or reduce the adhesion of biological material to surfaces. TLP coatings comprise a liquid fluorocarbon, perfluorocarbon, or mixture thereof, chemically tethered to a solid fluorinated polymer.[000115] In some aspects of the present disclosure, the liquid component of a TLP coating includes one or more solvents selected from: perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluorooctane, perfluorodecalin, perfluoroperhydrophenanthrene, perfluorooctylbromide, perfluoro tributyl amine, perfluorotripentyl amine, poly(hexafluoropropylene oxide), similar fluorinated polymers, and combinations thereof.[000116] In some aspects of the present disclosure, the solid component of a TLP coating comprises fluorinated polymers, which are fluoropolymers or perfluoropolymers selected from the group consisting of: perfluoroalkoxy alkanes; polytetrafluoroethylene; fluorinated ethylene propylene; expanded polytetrafluoroethylene; expanded fluorinated ethylene propylene; perfluoromethylvinylether; perfluoro elastomers; ethylene tetrafluoroethylene; poly vinylidene fluoride; fluoroelastomers; vinylidene fhioride-hexafluoropropylene fluoroelastomer; vinylidene fhioride-hexafluoropropylene / tetrafluoro ethylene / hexafluoropropylene fluoroelastomer terpolymer; and combinations thereof. In some aspects of the present disclosure, this TLP coating is applied according to the methods described in U.S Patent No. 9,932,484.[000117] In some aspects of the present disclosure, hollow tube bodies 110, 210 and 310 consist of a solid fluorinated polymer that serves as the solid component of the TLP coating. In other aspects, hollow tube bodies 110, 210 and 310 comprise a substantial concentration of a solid fluorinated polymer that serves as the solid component of the TLP coating. In some examples, the concentration of fluorinated polymer is between 80-100%, or between 60-80%, or between 40-60%, or between 20-40%, or between 0-20%, or greater than 85%, or greater than 90%, or greater than 95%.[000118] In some aspects, clog-resistant coatings 120, 230, 320, and 330 comprise both the solid and liquid components of a TLP coating, and hollow tube bodies 110, 210 and 310 arestructural. Tn some examples, these structural tube bodies comprise materials such as silicone, polymeric materials, ceramic materials, and other materials known in the art.[000119] FIG. 5 A provides a first example of the present invention as a subcutaneous lumbar shunt. CFMD 500 comprises a distal tip 501, a drainage tip 502, and a tube body 503. In some aspects of the present disclosure, substantially all of tube body 503 has a clog-resistant coating on the inner surface, outer surface, or both inner and outer surfaces. In some aspects of the present disclosure, only a selected portion of tube body 503 has a clog-resistant coating. In some aspects of the present disclosure, only the distal tip 501, drainage tip 502 or both distal and drainage tips have a clog-resistant coating.[000120] FIG. 5B demonstrates the use of CFMD 500 as a subcutaneous lumbar shunt. CFMD 500 drains CSF from the thecal sac 511 within lumbar region 510 into subcutaneous tissue region 520. Distal tip 501 can be inserted up to 10 cm or more into the thecal sac. The drained CSF is slowly resorbed by the body within subcutaneous tissue region 520. The size and distribution of subcutaneous tissue region 520 depends on many factors, including the location of the tissue on the body, the fluid flow rate, and the rate of resorption by the individual. While depicted here in the lumbar region of the back or stomach, subcutaneous tissue region 520 can be located anywhere on the body, such as the back, stomach, chest, abdomen, buttocks, legs, arms, neck, or cranium.[000121] FIG. 6 A provides a second example of the present invention as a subcutaneous lumbar shunt with multiple drainage channels. CFMD 600 comprises a distal tip 601, tube body 603, and multiple drainage tips 602a-c. Distal tip 600 can be inserted up to 10 cm or more into the thecal sac. Multiple drainage tips 602a-c enable distribution of CSF across a larger subcutaneous region to increase the resorption rate. Increasing the number of available shunt pathways may prevent or mitigate clogging. CFMD 600 is shown here with three drainage tips by way of example, but any number of drainage tips may be present, for instance, there may be two drainage tips 602, or there may be four or more. In some aspects of the present disclosure, drainage tips 602 are connected to a single tube. In some aspects of the present disclosure, each drainage tip is connected to an individual lumen within the FMD assembly. In some aspects of the present disclosure, substantially all of tube body 603 has a clog-resistant coating on the inner surface, outer surface, or both inner and outer surfaces. In some aspects of the present disclosure, only a selected portion of tube body 603 has a clog-resistant coating. In some aspects of the present disclosure, only the distal tip 601, drainage tip 502 or both distal and drainage tips have a clog-resistant coating.[000122] FIG. 6B demonstrates the use of CFMD 600 as a subcutaneous lumbar shunt. CFMD 600 drains CSF from the thecal sac 611 within lumbar region 610 into multiple subcutaneous tissue regions 620a-c. Without being bound by theory, increasing the number of drainage tips 602 increases the total resorption area to improve resorption rate and prevent clogging. While depicted here in the lumbar region of the back or stomach, subcutaneous tissue regions 620 can be located anywhere on the body, such as the back, stomach, chest, abdomen, buttocks, legs, arms, neck, or cranium. Subcutaneous tissue regions 620 may also be located in multiple regions on the body.[000123] FIG. 7A provides another example of the present invention as a subcutaneous lumbar shunt with an attached fluid reservoir. CFMD 700 comprises a distal tip 701, a drainage tip 702, a tube body 703, and a fluid reservoir 704. FIG. 7B demonstrates the use of CFMD 700 as a subcutaneous lumbar shunt within lumbar region 710. Fluid reservoir 704 provides an easy access point for sampling or tapping CSF. While shown here attached to the example of FIG. 5A, fluid reservoir 704 may be incorporated in any aspects of the present disclosure.[000124] FIG. 8 provides a first example of the present invention with an attached flow restrictor. CFMD 800 comprises a distal tip 801, a drainage tip 802, a tube body 803, and a flow restrictor 805 attached to tube body 803. Flow restrictor 805 controls the fluid flow rate through the FMD, and may be either adjustable or non-adjustable. Flow restrictor 805 may be, for instance, a valve, horizontal- vertical (HV) valve, smart valve, butterfly valve or bladder valve. While shown here attached to the example of FIG. 5A, flow restrictor 805 may be incorporated in any aspects of the present disclosure. In some aspects of the present disclosure, multiple flow restrictors may be incorporated into a CFMD. In some aspects of the present disclosure, one or more lumens, or one or more drainage tips, may incorporate an individual flow restrictor.[000125] FIG. 9 provides a second example of the present invention with a tapered end. CFMD 900 comprises a tapered end 901, an untapered end 902, and a tube body 903. Tapered end 901 controls the fluid flow rate through the FMD, and may be either adjustable or non- adjustable. Tapered end 901 may enable clearing of blockages within the FMD through insertion of a stylus by inhibiting the stylus from leaving the FMD and entering the body. While shown here at the distal tip of example FIG. 5A, tapered end 901 may be incorporated in any aspects of the present disclosure. Some examples of the present disclosure incorporate a tapered end at only one end, for instance the distal tip, and in other examples a tapered end may be incorporated in multiple ends, for instance in both the distal and drainage tips.ReferencesUshewokunze S, Haja Mydin HN, Prasad R, Mendelow AD. Lumbar subcutaneous shunt: a novel technique for therapeutic decision making in normal pressure hydrocephalus (NPH) and benign intracranial hypertension (BIH). Br J Neurosurg. 2008 Ocl;22(5):678- 81. doi: 10.1080 / 02688690802007883. PMID: 19016120.Marupudi NI, Harris C, Pavri T, Mell B, Singh R, Ham SD, Sood S. The role of lumboperitoneal shunts in managing chronic hydrocephalus with slit ventricles. J Neurosurg Pediatr. 2018 Dec l;22(6):632-637. dot: 10.3171 / 2018.6.PEDS17642. PMID: 30239284.Lo TY, Myles LM, Minns RA. Long-term risks and benefits of a separate CSF access device with ventriculoperitoneal shunting in childhood hydrocephalus. Dev Med Child Neurol. 2003 Jan;45(l):28-33. PMID: 12549752.Lalou AD, Czosnyka M, Garnett MR, Nabbanja E, Petrella G, Hutchinson PJ, Pickard JD, Czosnyka Z. Shunt infusion studies: impact on patient outcome, including health economics. Acta Neurochir (Wien). 2020 May;162(5): 1019-1031. doi: 10.1007 / s00701- 020-04212-0. Epub 2020 Feb 20. PMID: 32078047; PMCID: PMC7156359.

Claims

CLAIMSWhat is claimed is:

1. A clog -resistant fluid management device, the device comprising: a tube body comprising a distal tip and at least one drainage tip, an inner surface; and an outer surface; wherein the distal tip facilitates fluid flow between the tube body and a first location within a living organism, wherein the drainage tip facilitates fluid flow between the tube body and at least one second location within a living organism, wherein at least one portion of the inner surface, the outer surface, the distal tip, the drainage tip, or a combination thereof, comprises a clog-resistant coating, and wherein said tube body has an inner diameter of from greater than 0 mm to 5 mm.

2. The clog -resistant fluid management device of claim 1, wherein said clog-resistant coating is hydrophobic or superhydrophobic.

3. The clog -resistant fluid management device of any of claims 1-2, wherein the clog- resistant coating is durable.

4. The clog-resistant fluid management device of any of claims 1-3, wherein the clog- resistant coating is slippery.

5. The clog -resistant fluid management device of any of claims 1-4, wherein the clogresistant coating comprises a fluorinated surface covered with a fluorinated liquid.

6. The clog -resistant fluid management device of claim 5, wherein the fluorinated surface comprises fluoropolymers or perfluoropolymers selected from the group consisting of: perfluoroalkoxy alkanes; polytetrafluoroethylene; fluorinated ethylene propylene; expanded polytetrafluoroethylene; expanded fluorinated ethylene propylene; perfluoromethylvinylether; perfluoro elastomers; ethylene tetrafluoroethylene; polyvinylidene fluoride; fluoroelastomers; vinylidene fluoride-hexafluoropropylene fluoroelastomer; vinylidene fluoride- hexafluoropropylene / tetrafluoro ethylene / hexafluoropropylene fluoroelastomer terpolymer; and combinations thereof.

7. The clog-resistant fluid management device of any of claims 5-6, wherein the fluorinated liquid includes one or more solvents selected from: perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluorooctane, perfluorodecalin, perfluoroperhydrophenanthrene, perfluorooctylbromide, perfluoro tributyl amine, perfluorotripentyl amine, poly(hexafluoropropylene oxide) and combinations thereof.

8. The clog -resistant fluid management device of any of claims 1-7, wherein the first location within a living organism is one of the thecal sac, the ventricles, the central nervous system, the chest cavity, or the biliary duct.

9. The clog-resistant fluid management device of any of claims 1-8, wherein the at least one second location within a living organism is one or more of, or a combination of, a subcutaneous tissue region, peritoneum, pleural cavity, an atrium of the heart, or a vein.

10. The clog-resistant fluid management device of claim 9, wherein said subcutaneous tissue is located in one of the back, stomach, legs, pelvis, buttocks, chest, arms, neck, or cranium.

11. The clog-resistant fluid management device of any of claims 1-10, wherein the device extends from 1 cm to 15 cm into said first location within a living organism.

12. The clog-resistant fluid management device of any of claims 1-11, further comprising at least one flow restrictor.

13. The clog-resistant fluid management device of claim 12, wherein the flow restrictor is one of a nozzle, valve, HV valve, bladder valve, or tapered segment.

14. The clog-resistant fluid management device of any of claims 12-13, wherein at least one of the at least one flow restrictor is located at one of, or a combination of, the distal tip, drainage tip, or tube body.

15. The clog-resistant fluid management device of any of claims 1-14, further comprising at least one fluid reservoir.

16. The clog -resistant fluid management device of any of claims 1-15, wherein at least one portion of the tube body has a predefined shape.

17. The clog-resistant fluid management device of any of claims 1-16, comprising at least 1 drainage tip, wherein each of said drainage tips facilitates fluid flow to a different second location within said living organism.

18. The clog-resistant fluid management device of claim 17, wherein each of said different secondary locations is a subcutaneous tissue region.

19. The clog-resistant fluid management device of any one of claims 1-18, wherein said tube body has an inner diameter of from greater than 0 mm to 2 mm.

20. The clog -resistant fluid management device of any one of claims 1-19, wherein said tube body has an inner diameter between 0 mm and 1 mm.

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