WO2017173382A1 - Adsorbant sélectif de médiateurs de maladie - Google Patents

Adsorbant sélectif de médiateurs de maladie Download PDF

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Publication number
WO2017173382A1
WO2017173382A1 PCT/US2017/025570 US2017025570W WO2017173382A1 WO 2017173382 A1 WO2017173382 A1 WO 2017173382A1 US 2017025570 W US2017025570 W US 2017025570W WO 2017173382 A1 WO2017173382 A1 WO 2017173382A1
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WIPO (PCT)
Prior art keywords
carbonaceous material
anhydride
functional group
acid
bodily fluid
Prior art date
Application number
PCT/US2017/025570
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English (en)
Inventor
Carol A. Rae
Sergeui USMANOV
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ImMutriX Therapeutics, Inc.
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Publication of WO2017173382A1 publication Critical patent/WO2017173382A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/20—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising free carbon; comprising carbon obtained by carbonising processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/3085—Chemical treatments not covered by groups B01J20/3007 - B01J20/3078

Definitions

  • compositions, systems, and methods for the selective removal of biological molecules from bodily fluids More particularly disclosed herein are compositions methods and systems for the treatment of one or more pathophysiological conditions.
  • Bodily fluids are liquids originating from inside the bodies of living humans. They include fluids that are excreted or secreted from the body. In addition to their roles in disease transmission, numerous bodily fluids during a pathophysiological event serve as repositories for molecules that function as disease mediators or disease-related toxins.
  • disease-related toxin is used to refer to the molecule or collection of molecules that are associated with the pathophysiology the subject is seeking treatment for. Attenuation of the adverse events associated with the persistence of these disease-related toxins at levels detrimental to a subject's physiological well-being holds continuing potential for development into a multitude of treatment options.
  • Figure 1 depicts an aspect of an apparatus of the type disclosed herein.
  • Figure 2 is a plot of the covalent bonding (indicated by FTIR spectra) observed in solution as a function of ultrasonic frequency utilized.
  • Figure 3 is a plots of the covalent bonding (indicated by FTIR spectra) observed in solution as a function of ultrasonic power utilized.
  • a carbonaceous material comprising at least 80 wt. % pure carbon and a functional group, wherein the functional group has been chemically-associated with the carbonaceous material by ultrasonication.
  • a method comprising obtaining an uncleansed bodily fluid from a subject; contacting the uncleansed bodily fluid with a carbonaceous material comprising at least 80 wt.% pure carbon and a functional group, wherein the functional group has been chemically- associated with the carbonaceous material by ultrasonication; obtaining a cleansed bodily fluid subsequent to the contacting; and recovering the cleansed bodily fluid.
  • compositions and methodologies useful treating pathophysiologies associated with the persistence of disease-related toxins in the bodily fluids of a subject comprises any and all organisms and includes the term “patient.”
  • a subject to be treated according to the methods described herein may be one who has been diagnosed by a medical practitioner as having a disease, disorder, or dysfunction amenable to treatment with the methodologies disclosed herein.
  • treating refers to utilizing the disclosed methodologies and compositions for prophylactic and/or therapeutic purposes.
  • treating refers to a subject undergoing, either for therapeutic or prophylactic purposes, the methodologies disclosed herein.
  • the method comprises exposure of a bodily fluid to a selectively adsorbent carbon (SAC) configured to retain some disease-related toxin while concomitantly excluding molecules/materials beneficial to the physiological well-being of the subject.
  • SAC selectively adsorbent carbon
  • a bodily fluid comprising a disease mediator or disease-related toxin e.g., an uncleansed bodily fluid
  • a selectively adsorbent carbon SAC
  • an amount of the disease mediator or disease related toxin of the uncleansed bodily fluid being adsorbed by the selectively adsorbent carbon (SAC), thereby obtaining a bodily fluid with a reduced amount of disease mediator or disease-related toxin (e.g., a cleansed bodily fluid).
  • the disease-related toxin as used herein may refer to a single compound, molecule, toxin, or biomolecule or may be used herein to refer to a collection of compounds, toxins, molecules or biomolecules that can be selectively adsorbed by the SAC when compared to the absorption of other compounds, molecules, toxins or biomolecules present in the bodily fluid.
  • the SAC retains greater than about 70% of the total amount of disease- related toxin present in the volume of bodily fluid treated by exposure to the SAC.
  • the SAC retains greater than about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the total amount of disease-related toxin present in the volume of bodily fluid treated by exposure to the SAC.
  • the SAC has a reduced binding of molecules either (i) not contributing to the disease or disorder of the subject or (ii) contributing to the physiological well-being of the subject.
  • the SAC may display nonspecific binding of molecules of less than about 20% such that of the total number of molecules bound less than about 20% of the molecules by total moles of molecules bound are (i) not contributing to the disease or disorder of the subject or (ii) contributing to the physiological well-being of the subject.
  • the SAC is prepared from a synthetic carbon particle containing micro-, meso- and macropores.
  • a synthetic carbon particle of the type disclosed herein may be prepared using any suitable methodology.
  • the synthetic carbon particle is prepared using a phenolic resin.
  • micropore refers to a pores with diameter ⁇ 2 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC.
  • meopore refers to pores with diameter from ca. 2 nm to ca. 50 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC.
  • macropore refers to pores with diameters larger than 50 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC.
  • macroporous beads they are located within beads and formed by pore-formers.
  • the synthetic carbon particle has a first type of macropores wherein the macroporous pore size ranges from about 50 nm to about 1000 nm, alternatively from about 70 nm to about 200 nm. These macropores are very effective in adsorption of cytokines.
  • the synthetic carbon particle has a second type of macropores wherein the macroporous pore size ranges from about 75 ⁇ to about 1000 ⁇ , alternatively from about 100 ⁇ to about 750 ⁇ , or alternatively from about 200 ⁇ to about 500 ⁇ .
  • synthetic carbon particles suitable for use in the present disclosure are characterized by macropore sizes ranging from about 0.05 ⁇ to about 1 ⁇ .
  • a synthetic carbon particle suitable for use in the present disclosure may comprise an synthetic carbon particle having at least two distributions of macroporous pore sizes.
  • the synthetic carbon particle may comprise a first population having a macroporous pore size denoted x and a second population having a macroporous pore size y where the synthetic carbon particle provides a mixture having a ratio of x/y of about 1; alternatively about 5, alternatively about 10, alternatively about 20; alternatively about 50, or alternatively about 100.
  • the synthetic carbon particle comprises a mixture of two populations wherein the pore size of the first population is approximately twice the pore size of the second population. In some aspects, the synthetic carbon particle comprises a mixture of three populations where the pore size of a first population is approximately twice the pore size of the second population and the pore size of the third population is approximately two and a half times the pore size of the second population.
  • a synthetic carbon particle suitable for use in the present disclosure may have any shape compatible with the compositions and methodologies disclosed herein.
  • the shape of the synthetic carbon particle may be that of an irregular granule, a low angularity shape, spherical (e.g., bead), pellet, minilith, monolith, etc.
  • the present disclosure may refer to the use of beads of the SCB however it is to be understood the synthetic carbon particle may be of any suitable shape.
  • the synthetic carbon particles may be formed using any suitable methodology to results in a material having the properties disclosed herein.
  • a precursor resin formulation is used which comprises a large proportion of pore former, e.g. 250 parts ethylene glycol or other pore former to 100 parts of resin-forming components.
  • a mesoporous resin may be formed by condensing a nucleophilic component which comprises a phenolic compound or a phenol condensation prepolymer with at least one electrophilic cross-linking agent selected from formaldehyde, paraformaldehyde, furfural and hexamethylene tetramine in the presence of a pore-former selected from the group consisting of a diol (e.g. ethylene glycol), a diol ether, a cyclic ester, a substituted cyclic ester, a substituted linear amide, a substituted cyclic amide, an amino alcohol and a mixture of any of the above with water to form a resin.
  • a diol e.g. ethylene glycol
  • a diol ether e.g. ethylene glycol
  • a diol ether e.g. ethylene glycol
  • a diol ether e.g. ethylene glycol
  • the pore-former is present in an amount effective to impart meso- or macroporosity to the resin (e.g. at least 120 parts by weight of the pore former being used to dissolve 100 parts by weight of the total resin forming components, i.e. nucleophilic component plus electrophilic component), and it is removed from the porous resin after condensation by cascade washing with water or by vacuum drying.
  • the resulting resin may be carbonized by heating in an inert atmosphere to a temperature of at least 600°C to give a material having a bimodal distribution of pores, the pore structure as estimated by nitrogen adsorption porosimetry comprising micropores and mesopores or macropores.
  • the value for the differential of pore volume with respect to the logarithm of pore radius (dV/dlogR) for the mesopores is greater than 0.2 for at least some values of pore size in the range 20-500 A.
  • the mesoporous carbon may have a BET surface area of 250- 800 m 2 /g without activation. It may be activated by heating it at high temperature in the presence of carbon dioxide, steam or a mixture thereof, e.g. by heating it in carbon dioxide at above 800 °C, or it may be activated by heating it in air at above 400 °C. It may then have surface areas of up to 2000 m 2 /g and even higher e.g. 1000-2000 m 2 /g. As used herein the term "BET surface area" is determined by the Brunauer, Emmett, and Teller (BET) method according to ASTM D 1993 -91, see also ASTM D6556-04.
  • Resins for making carbonaceous material can be prepared from any of the starting materials such that the nucleophilic components may comprise phenol, bisphenol A, alkyl phenols e.g. cresol, diphenols e.g. resorcinol and hydroquinione and aminophenols e.g. m-amino-phenol.
  • the nucleophilic components may comprise phenol, bisphenol A, alkyl phenols e.g. cresol, diphenols e.g. resorcinol and hydroquinione and aminophenols e.g. m-amino-phenol.
  • a phenolic Novolac or other similar oligomeric starting material which because it is already partly polymerized makes polymerization to the desired resin a less exothermic and hence more controllable reaction.
  • the preferred Novolacs have average molecular weights (AMW) in the range of from 300 to 3000 prior to cross-linking (corresponding to a DP with respect to phenol of about 3-30). Where Novolac resins are used, they may be solids with melting points in the region of 100 °C. Novolac resins of AMW less than 2000 and preferably less than 1500 form resins which on carbonization tend to produce carbons with desired pore size distributions using lower amounts of pore former.
  • AMW average molecular weights
  • Novolacs are thermally stable in that they can be heated so that they become molten and cooled so that they solidify repeatedly without structural change. They are cured on addition of cross-linking agents and heating. Fully cured resins are infusible and insoluble. Whilst commercial Novolacs are largely produced using phenol and formaldehyde, a variety of modifying reagents can be used at the pre-polymer formation stage to introduce a range of different oxygen and nitrogen functionalities and cross-linking sites. These include but are not limited to: (a) Dihydric phenols e.g. resorcinol and hydroquinone. Both are more reactive than phenol and can lead to some cross-linking at the pre-polymer production stage.
  • Dihydric phenols e.g. resorcinol and hydroquinone. Both are more reactive than phenol and can lead to some cross-linking at the pre-polymer production stage.
  • Nitrogen containing compounds that are active in poly condensation reactions such as urea, aromatic (aniline, m-amino phenol) and heteroaromatic (melamine) amines. These allow the introduction of specific types of nitrogen functionality into the initial polymer and final carbon and influence the development of the mesoporous structure of both the resins and the final carbons.
  • Nitrogen containing nucleophilic modifying reagents which can be used possess two or more active sites and are more reactive in condensation reactions than phenol or Novolacs. It means that they are first to react with primary cross-linking agents forming secondary cross-linking agents in situ.
  • the nucleophilic component may be provided alone or in association with a polymerization catalyst which may be a weak organic acid miscible with the Novolac and/or soluble in the pore former e.g. salicylic acid, oxalic acid or phthalic acid.
  • the concentration of Novolac in the pore former may be such that when combined with the solution of cross-linking agent in the same pore former the overall weight ratio of pore former to (Novolac+cross-linking agent) is at least 125: 100 by weight.
  • the actual ratios of Novolac:pore former and cross-linking agen pore former are set according to convenience in operation by the operational requirements of a bead production plant and are controlled by the viscosity of the Novolac:pore former solution such that it remains pumpable and by the ratio of cross-linking agen pore former such that the cross-linking agent remains in solution throughout the plant.
  • the cross-linking agent is normally used in an amount of from 5 to 40 parts by weight (pbw) per 100 parts by weight of the nucleophilic components e.g. Novolac. It may be, for example, an aldehyde e.g. formaldehyde or furfural, it could be hexamethylenetetramine (hexamine), or hydroxymethylated melamine.
  • Hexamine is preferably used as cross-linking agent. In aspects requiring a completely cured resin, it is preferably used for cross-linking Novolac resin at a proportion of 10 to 25 pbw e.g. about 15 to 20 pbw hexamine per 100 pbw of Novolac. This ensures formation of the solid resin with maximal cross-linking degree and ensures the stability of the mesopore structure during subsequent removal of the pore former.
  • the pore former also acts as solvent.
  • the pore former is preferably used in sufficient quantities to dissolve the components of the resin system, the weight ratio of pore former to the total components of the resin system resin being preferably at least 1.25: 1.
  • the pore former may be, for example, a diol, a diol-ether, a cyclic ester, a substituted cyclic or linear amide or an amino alcohol e.g. ethylene glycol, 1,4-butylene glycol, di ethylene glycol, triethylene glycol, ⁇ -butyrolactone, propylene carbonate, dimethylformamide, N-methyl-2- pyrrolidinone and monoethanolamine, ethylene glycol being preferred, and where the selection is also limited by the thermal properties of the solvent as it should not boil or have an excessive vapor pressure at the temperatures used in the curing process.
  • a diol e.g. ethylene glycol, 1,4-butylene glycol, di ethylene glycol, triethylene glycol, ⁇ -butyrolactone, propylene carbonate, dimethylformamide, N-methyl-2- pyrrolidinone and monoethanolamine, ethylene glycol being preferred, and where the selection is also limited by the thermal properties of the solvent as it should not
  • the pore former In the presence of a low level of pore former the pore former is compatible with, and remains within, the cross-linked resin domains, (e.g., ⁇ 120 parts/100 parts Novolac for the Novolac-Hexamine-Ethylene Glycol reaction system), whilst the remainder forms a solution with the partially cross-linked polymer between the domains.
  • the pore former adds to the light polymer fraction increasing the volume of material in the voids between the domains that gives rise to the mesoporosity and/or macroporosity.
  • the higher the pore former content the wider the mesopores, up to macropores, and the higher the pore volume.
  • This phase separation mechanism provides a variety of ways of controlling the pore development in the cross-linked resin structures. These include chemical composition and concentration of the pore former; chemical composition and quantity of the cross-linking electrophilic agents, presence, chemical nature and concentration of modifying nucleophilic agents, chemical composition of phenolic nucleophilic components (phenol, Novolac), the presence of water within the solvent and concentration of any curing catalyst if present.
  • Production of the bead form may be by pouring a solution of a partially cross-linked pre- polymer into a hot liquid such as mineral oil containing a dispersing agent and stirring the mixture.
  • the pre-polymer solution forms into beads which are initially liquid and then, as curing proceeds, become solid.
  • the average bead particle size is controlled by several process parameters including the stirrer type and speed, the oil temperature and viscosity, the pre-polymer solution viscosity and volume ratio of the solution to the oil and the mean size can be adjusted between 5 ⁇ and 2000 ⁇ although in practice the larger bead sizes are difficult to achieve owing to problems with the beads in the stirred dispersion vessel.
  • the beads can then be filtered off from the oil.
  • Discrete solid beads of polymeric material e.g. phenolic resin having a porous structure
  • the process comprises the steps of: (a) combining a stream of a polymerizable liquid precursor e.g. a Novolac and hexamine as cross-linking agent dissolved in a first polar organic liquid e.g. ethylene glycol with a stream of a liquid suspension medium which is a second non-polar organic liquid with which the liquid precursor is substantially or completely immiscible e.g.
  • transformer oil containing a drying oil (b) mixing the combined stream to disperse the polymerizable liquid precursor as droplets in the suspension medium e.g. using an in-line static mixer; (c) allowing the droplets to polymerize in a laminar flow of the suspension medium so as to form discrete solid beads that cannot agglomerate; and (d) recovering the beads from the suspension medium.
  • the pore former comprises a polar organic liquid e.g. ethylene glycol chosen in combination with dispersion medium which is a non-polar organic liquid so as to form a mainly or wholly immiscible combination, the greater the incompatibility between the pore former which forms the dispersed phase and the dispersion medium, the less pore former becomes extracted into the dispersion medium.
  • the pore former desirably has a greater density than the dispersion medium with which it is intended to be used so that droplets of the pore former containing dissolved resin-forming components will pass down a column more rapidly than a descending flow of dispersion medium therein.
  • the pore former should also, in the case of phenolic resins, be compatible with water and/or other minor condensation products (e.g. ammonia) which are formed by elimination as polymerization proceeds, and the pore former is preferably highly miscible with water so that it can be readily removed from the polymerized resin beads by washing.
  • minor condensation products e.g. ammonia
  • the dispersion medium is a liquid which can be heated to the temperature at which curing is carried out e.g. to 160 °C without boiling at ambient pressure and without decomposition and which is immiscible with ethylene glycol and with the dissolved components therein.
  • It may be hydrocarbon-based transformer oil which is a refined mineral oil and is a by-product of the distillation of petroleum. It may be composed principally of C.15-C.40 alkanes and cycloalkanes, have a density of 0.8-0.9 depending upon grade and have a boiling point at ambient pressure of 260- 330 °C, also depending upon grade.
  • Transformer oil has a viscosity of about 0.5 poise at 150 °C which is a typical cure temperature.
  • Transformer oil or other dispersion medium may be used in volumes 3-10 times the volume of the combined streams of nucleophilic precursor and crosslinking agent e.g. about 5 times.
  • Preferred dispersing agents which are dissolved in the dispersion medium before that medium is contacted with the reaction mixture to be dispersed therein to retard droplet coalescence are either sold as drying oils e.g. Danish oil or are produced by partially oxidizing naturally occurring precursors such as tung oil, linseed oil etc.
  • the dispersing agents are consumed as the process proceeds, so that if the dispersion medium is recycled, dispersing agent in the recycled oil stream should be replenished.
  • the dispersing agent is conveniently supplied as a stream in solution in the dispersion medium e.g. transformer oil and e.g.
  • the resin beads formed as described above may be carbonized and optionally activated.
  • carbonization and activation may comprise supplying the material to an externally fired rotary kiln maintained at carbonizing and activating temperatures, the kiln having a downward slope to progress the material as it rotates, the kiln having an atmosphere substantially free of oxygen provided by a counter-current of steam or carbon dioxide, and annular weirs being provided at intervals along the kiln to control progress of the material.
  • a synthetic carbon particle suitable for use in the present disclosure is characterized by a microporous/macroporous structure.
  • a synthetic carbon particle suitable for use in the present disclosure is characterized by a microporous/mesoporous structure.
  • a synthetic carbon particle suitable for use in the present disclosure is characterized by a mesoporous/macroporous structure.
  • a synthetic carbon particle suitable for use in the present disclosure is characterized by a macroporous(x)/macroporous(y) structure.
  • a method of preparing the SAC comprises (i) contacting a synthetic carbon particle of the type disclosed herein with a reaction medium containing a solvent and an oligomerizable monomer to form a reaction mixture (ii) exposing the reaction mixture to ultrasonic energy under conditions sufficient associate the monomer with the synthetic carbon particle forming a reaction product comprising a SAC; and (iii) recovering the reaction products.
  • the monomer is a vinyl monomer.
  • vinyl monomers subjected to acoustic cavitation in liquids may undergo oligomerization and/or polymerization in the absence of chemical initiators or stabilizers.
  • the monomer comprises ethylene, ethylene glycol, propylene, acrylates such as methyl methacrylate or n-butyl acrylate, vinyl acetates, acrylamide, ethylene oxide, or combinations thereof.
  • any monomer capable of oligomerization and/or polymerization by exposure to ultrasonic energy may be included in the reaction medium.
  • the reaction medium is exposed to ultrasonic energy having a frequency of equal to or greater than about 20 kilo Herz (kHz), alternatively greater than about 25 kHz, alternatively greater than about 30 kHz, alternatively greater than about 35 kHz, alternatively greater than about 40 kHz, alternatively greater than about 40 kHz, alternatively greater than about 45 kHz, or alternatively greater than about 50 kHz.
  • the reaction products comprise the synthetic carbon particle, monomers associated with the synthetic carbon particle (m-SAC), unreacted monomers, oligomers, oligomers associated with the synthetic carbon particle (o-SAC), polymers, and polymers associated with the synthetic carbon particle (p-SAC).
  • the term "associated” refers to the formation of a chemical link or between the synthetic carbon particle and the molecule (e.g., monomer or oligomer).
  • the molecules/moieties may be associated with the SAC (to form for example m-SAC, o-SAC, or p-SAC) such that these moieties are distributed throughout the surface and/or interior of the SAC.
  • the reaction products comprise less than about 1 wt.% polymers or p-SAC.
  • a polymer can be denoted Xn where X represents the monomer utilized in the reaction and n is greater than 6.
  • the reaction products comprise from about 0.1 wt.% to about 5 wt.%) m-SAC, and from about 0.1 wt.%> to about 5 wt.% oligomers.
  • the remainder of the reaction products comprises o-SAC.
  • o-SAC Alternatively greater than about 80 wt.%> o- SAC, alternatively greater than about 85 wt.% o-SAC, or alternatively greater than about 90 wt.%> o-SAC.
  • the presently disclosed methodology contemplates the ultrasonic production of areas of high and low pressure on the synthetic carbon particle surface resulting the deformation of pores in response to the acoustic energy (e.g., an accordion effect) in the affected dimensions and geometries of substrate surface.
  • the mass transfer momentum of the acoustic energy wave moves the precursor molecules (e.g., vinyl monomer) in a wave-like fashion toward the carbon surface essentially driving the precursor molecules toward the pores of the synthetic carbon particles.
  • the precursor molecule experiences local micro-level compression and distortion from dynamically-deforming synthetic carbon particles that produce a high probability of chemical bonding between the synthetic carbon particles and precursor molecules as the reaction distances are dramatically reduced during the compression cycles. Additionally, other reactive sites on the synthetic carbon particles become exposed during the expansion cycles. Trapped and bounded precursor molecules experience redistribution of electron densities within a molecule, as some of the inner-molecule shared electrons become involved in covalent bounding with the synthetic carbon particle. This distortion of the inner molecules' electronic field opens opportunities for a variety of additional chemical bonding with external molecules in relation to the synthetic carbon particle where bound precursor perform the function of an anchored interface between external functional molecules and the synthetic carbon particle.
  • the moieties associated with the SAC are chemically reactive.
  • chemically reactive refers to the ability of the moieties associated with the SAC (e.g., oligomer associated with SAC or o-SAC) to be further chemically modified to include one or more functional groups and generate a functionalized reaction product that associates with some user and/or process- desired molecule.
  • functionalized reaction product is meant that the reaction product (e.g., o- SAC) is contacted with a functional group, and optionally a catalyst, heat, initiator, or free radical source to cause all or part of the functional group to incorporate, graft, bond to, physically attach to, and or chemically attach to the SAC.
  • ком ⁇ онент is meant any compound with a molecular weight of 1000 g/mole or less that contains a heteroatom and or an unsaturation.
  • the functional group may be a compound containing a heteroatom, such as maleic anhydride.
  • functional groups include organic acids, organic amides, organic amines, organic esters, organic anhydrides, organic alcohols, organic acid halides (such as acid chlorides, acid bromides, etc.) organic peroxides,
  • suitable functional groups include unsaturated carboxylic acids, esters of the unsaturated carboxylic acids, acid anhydrides, di-esters, salts, amides, imides, aromatic vinyl compounds hydrolyzable unsaturated silane compounds and unsaturated halogenated hydrocarbons.
  • unsaturated carboxylic acids and acid derivatives include, but are not limited to maleic anhydride, citraconic anhydride, 2-methyl maleic anhydride, 2-chloromaleic anhydride, 2,3-dimethylmaleic anhydride, bicyclo[2.2.1]-5-heptene-2,3- di carboxylic anhydride and 4-m ethyl -4-cyclohexene-l,2-dicarboxylic anhydride, acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, citraconic acid, mesaconic acid, crotonic acid, bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic acid anhydride, 1 ,2,3,4,5,8,9, 10- octahydronaphthalene-2,3 dicarboxylic acid anhydride, 2-oxa-l,3-diketospiro(4.4)non-7-ene, bicyclo[2.2
  • Nonlimiting examples of the esters of the unsaturated carboxylic acids include methyl acrylate, ethyl acrylate, butyl acrylate, methyl methacrylate, ethyl methacrylate and butyl methacrylate and the like.
  • any suitable methodology may be utilized to functionalize the reaction products associated with the SAC.
  • the monomer may be a methyl acrylate.
  • the oligomer may be terminated by allyl groups.
  • allyl alcohol or 1,2- epoxy-5-hexene monomers which are not reactive by ultrasonication, can be added, alcohol and epoxy functionalities respectively may be incorporated at the oligomer chain end.
  • a SAC of the type disclosed herein, with or without an associated oligomer, with or without functionalization may be utilized in a therapy to address the detrimental aspects of a disease state, disorder, or dysfunction, collectively referred to as a medical condition.
  • a SAC is contacted with a bodily fluid such as whole blood, diluted blood, heparinized blood, plasma, frozen plasma and/or cerebral/spinal liquid.
  • a bodily fluid such as whole blood, diluted blood, heparinized blood, plasma, frozen plasma and/or cerebral/spinal liquid.
  • the SAC may be a component of an extracorporeal apparatus.
  • the apparatus 300 comprises an inlet 305 in fluid communication with a pump 360 which regulates access and fluid communication with conduit 315.
  • the apparatus 300 may be connected to a subject through establishing a means of bodily fluid flow from the subject to inlet 305.
  • Any suitable container 355 may be used as a reservoir from which to establish a means of bodily fluid flow from the subject to the inlet 305.
  • a methodology of the type disclosed herein comprises establishing fluid communication between a subject's bodily fluid flow 355 and the inlet 305 of the apparatus 300.
  • the pump 360 regulates the flow of the subject's bodily fluid to the remainder of the apparatus 300 through conduit 315.
  • Conduit 315 may be a pipe or flow line comprised of material suitable for use in the methodologies disclosed herein.
  • the subject's bodily fluid is allowed to flow through conduit 315 until it reaches valve 380 which when in the on position allows the bodily fluid flow to enter column A 310 in a particular flow direction F 390.
  • Bodily fluid may be pumped through column A 310 and exit the column thorough an outlet regulated by a valve 385.
  • Bodily fluid exiting from column A 310 through the outlet regulated by valve 385 may enter conduit 395 where it is pumped to inlet port 340 whose access is regulated by valve 345.
  • valve 345 When valve 345 is in the on position, the bodily fluid may be pumped from inlet port 340 to column B 350 where it moves in flow direction G 342 through column B 350 to outlet port 348 which is regulated by valve 352.
  • valve 352 When valve 352 is in the on position the bodily fluid may flow from column B 350 into conduit 315.
  • the subject's bodily fluid is allowed to flow through conduit 315 until it reaches inlet port 360 which is regulated by valve 362 which when in the on position allows the bodily fluid flow to enter column C 370 in a particular flow direction H 375.
  • the bodily fluid may exit column C 370 via outlet port 378 which is regulated by valve 376 which when in the on position allows the bodily fluid to flow into conduit 395 and back to the subject or a container vessel 392.
  • the rate of flow of a bodily fluid (e.g., bodily fluid) through apparatus 300 may be regulated to provide some user and/or process goal.
  • the rate of bodily fluid flow through apparatus 300 may range from about 1 mL/min to about 300 mL/min, alternatively from about 25 mL/min to about 300 mL/min, alternatively from about 25 mL/min to about 150 mL/min, or alternatively from about 150 mL/min to about 300 mL/min.
  • treatment of a subject of the type disclosed herein may require the subject be in fluid communication with apparatus 300 for a period of time ranging from about 1 hour to about 24 hours, alternatively from about 1 hour to about 12 hours, alternatively from about 1 hour to about 6 hours, alternatively from about 1 hour to about 4 hours, or alternatively less than about 4 hours.
  • Figure 1 presents an aspect of an apparatus suitable for use in the present disclosure. Additional routine modifications to the apparatus are contemplated by the present disclosure.
  • the apparatus may contain more or less than the 3 columns depicted in Figure 1 or the columns may be disposed in positions other than perpendicular to conduits 315 and 395.
  • the apparatus 300 may be associated with a computer system.
  • disease-related toxins that may be selectively removed by the present compositions and methodologies include small inorganic compounds such as nitric oxide, nitrogen dioxide, nitrate, hydrogen peroxide; billirubin, cretinine, heme; LPS-endotoxin; growth factors such as vascular endothelia growth factor, epidermal cell- derived factor, fibroblast growth factor, nerve growth factor, growth-regulated protein alpha, Interferon-inducible T-cell alpha chemoattractant, stem cell factor, transforming growth factor beta; C-reactive protein, transforming growth factor-alpha, and transforming growth factor beta; cytokines such as C-reactive protein, transforming growth factor-alpha, interleukin 1-beta; interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin 12, interleukin
  • a method of treating a subject comprises subjecting at least a portion of the subject's blood to contact with an extracorporeal device comprising the a SAC of the type disclosed herein.
  • the subject's blood may be characterized by an initial circulating blood level of disease mediators designated x. It is to be understood the subject's blood may be further characterized by the presence of desirable blood components present in an amount a.
  • a cleansed product is obtained, which may be characterized by a circulating blood level of disease mediators designated y where y is less than x and a level of desirable blood components b where a is about equal to b.
  • y may have a value that is that is from about 10% to about 90% less than x, alternatively from about 20% to about 80%) less than x, or alternatively from about 30%> to about 70% less than x.
  • y has a value that is at least one order of magnitude less than x.
  • b has a value that is ⁇ 20% of the value of a, alternatively ⁇ 10% the value of a.
  • the compositions, methodologies, and systems disclosed herein result in the selective reduction of circulating blood level of disease mediators with a concomitant retention of desirable blood components.
  • compositions and methodologies disclosed herein may be utilized in the treatment of a subject having a medical condition.
  • the medical condition is selected from the group consisting of metabolic disorders, inflammatory diseases, degenerative diseases, neoplastic diseases, and systemic immune response (SIRS) disorders or SIRS-like disorders and the bodily fluid is plasma with blood cellular components.
  • inflammatory diseases refer to those in which the body reacts to an injurious agent by means of inflammation.
  • degenerative diseases refer to diseases where the primary abnormality is degeneration of a part of the body.
  • metabolic diseases refer to those where the primary abnormality is a disturbance in an important metabolic process in the body.
  • neoplastic disease refers to a disease where the primary abnormality is unregulated cell growth leading to the formation of various types of benign and malignant tumors.
  • medical conditions selected from the group consisting of metabolic disorders, inflammatory diseases, degenerative diseases, neoplastic diseases and SIRS or SIRS-like disorders are collectively termed Class A disorders.
  • the medical condition is a neoplastic disorder such as cancer. Cancer is a major public health problem in the United States and many other parts of the world. In 2013, in the United States alone, there were 1,660,290 new occurrences. Cancer is the second most common cause of mortality.
  • Chronic inflammation can be oncogenic by various mechanisms: (i) induction of genomic instability, (ii) increasing angiogenesis, (iii) altering the genomic epigenetic state and (iv) increasing cell proliferation. Chronic inflammation also induces anemia and cachexia observed in cancer.
  • the medical condition is a metabolic disorder resulting in chronic kidney disease (CKD).
  • CKD is defined as kidney damage or a glomerular filtration rate (GFR) below 60 and is a result of metabolic syndrome.
  • GFR is a measure of the level of kidney function.
  • CKD affects 20 million Americans (1 in 9 adults) and another 20 million are at increased risk. Hemodialysis does not stop progression to end-stage and patients are at high risk for developing anemia and other comorbidities. Early treatment of anemia is recommended to minimize the symptoms and improve quality of life. The treatment is difficult, since anemia in CKD is mainly not erythropoietin (EPO) deficient. In fact, CKD patients suffer from significantly higher oxidative stress and systemic inflammation.
  • EPO erythropoietin
  • TGF- ⁇ levels are about 3 times those of the controls.
  • High TGF- ⁇ levels prevent erythropoiesis.
  • TNF-a, IL- ⁇ and IFN- ⁇ which showed to be strong anti-erythropoietic agents, are also elevated.
  • inflammatory cytokines TNF-a, IL- ⁇ , IL-6, IL-8, IFN- ⁇
  • TGF- ⁇ superfamily besides CKD anemia, mediates nephrosclerosis.
  • Other nephrotoxic molecules include uric acid, free hemoglobin, CRP, and active lipid- (i.e., 8-isoprostane), oxygen- and nitrogen- species.
  • the medical condition is a degenerative disorder such as cardiovascular disease and the bodily fluid is plasma with blood cellular components.
  • Cardiovascular diseases are the leading cause of death in the United States. They kill an estimated 17 million people worldwide each year. Cardiovascular diseases are a group of disorders of the heart and blood vessels and include: (i) coronary heart disease, (ii) cerebrovascular disease, (iii) peripheral arterial disease, (iv) rheumatic heart disease, (v) congenital heart disease, (vi) deep vein thrombosis and (vii) pulmonary embolism. Heart attacks and strokes are caused by a blockage that prevents blood from flowing to the heart or brain.
  • cardiovascular disease formerly considered only as a bland lipid storage disease, but actually involves an ongoing inflammatory response.
  • the mediators of cardiovascular diseases include: cholesterol, triglyceride, LDL, VLDL, ox-LDL, other biologically active lipids and pro-inflammatory mediators such as C-reactive protein (CRP) and cytokines.
  • CRP C-reactive protein
  • cytokines pro-inflammatory mediators such as C-reactive protein (CRP) and cytokines.
  • CRP C-reactive protein
  • cytokines C-reactive protein
  • cardiovascular disease may be treated by lifestyle modifications aimed at slowing or stopping its progression.
  • surgical intervention or a non-surgical procedure may be necessary.
  • the medical condition is a SIRS or SIRS-like disorder and the bodily fluid is plasma with blood cellular components.
  • SIRS Systemic Inflammatory Response Syndrome
  • sepsis has a high mortality rate at approximately 25-50%.
  • Septic shock is characterized by hypotension, defective 02 binding, lactic acidemia and myocardial depression.
  • LPS circulating endotoxin
  • SIRS single respiratory distress syndrome
  • SIRS is a common complication in other medical conditions that has a high mortality rate, particularly burns. According to CDC deaths from fires and burns are the third leading cause of fatal home injury. On average in the United States, someone dies in a fire every 169 minutes, and someone is injured every 30 minutes. Fire and burn injuries represent 1% of the incidence of injuries and 2% of the total costs of injuries, or $7.5 billion each year.
  • Burn injuries are characterized by (i) endotoxemia that results from bacterial translocation and leads to hypotension and end organ hypoperfusion, (ii) oxidative stress, (iii) SIRS, (iv) capillary leak syndrome (CLS), (v) hypoalbuminemia and (vi) immunosuppression with depressed T-cell function that results in infections.
  • These pathological responses are mediated by circulating endotoxin that activates phagocytes to release TNF-a that in turn activates NOS converting L-arginine to NO.
  • NO stimulates production of cGMP that lowers intracellular calcium producing hypotension and myocardial depression.
  • Acute respiratory distress syndrome (ARDS) is also commonly observed in burns.
  • Hepatic encephalopathy which accompanies many disease states such as neoplastic, metabolic, traumatic, infectious, and toxicosis, is a condition with significant morbidity and mortality.
  • HE is caused by an accumulation of circulating toxins that are damaging to CNS, particularly ammonia (NH 3 ), marcaptans and phenol, normally removed by the liver.
  • NH 3 ammonia
  • marcaptans and phenol
  • the medical condition is the ingestion of poisons and/or drugs at levels that are harmful to the body and the bodily fluid is plasma with blood cellular components.
  • a medical condition arising from the ingestion of poisons and/or drugs at high level are termed Class 1 conditions. Every day in the United States, 120 people die as a result of drug overdose, and another 7,000 are treated for the misuse or abuse of drugs. Nearly 9 out of 10 poisoning deaths are caused by drugs. In 2013, of the 43,982 drug overdose deaths in the United States, 22,767 (51.8%) were related to pharmaceuticals.
  • acetaminophen which block the action of the neurotransmitter acetylcholine (such as atropine, scopolamine, belladonna, antihistamines, and antipsychotic agents), antidepressant drugs such as amitriptyline, desipramine, and nortriptyline); cholinergic drugs, which stimulate the parasympathetic nervous system (carbamate, pilocarpine, etc.); cocaine and crack cocaine; depressant drugs (tranquilizers, antianxiety drugs, sleeping pills); digoxin, a drug used to regulate the heart; narcotics or opiates (heroin, morphine, codeine, etc.), salicylates (aspirin) and many others.
  • acetaminophen which block the action of the neurotransmitter acetylcholine (such as atropine, scopolamine, belladonna, antihistamines, and antipsychotic agents), antidepressant drugs such as amitriptyline, des
  • a method of the present disclosure comprise subjecting a carbonaceous material to ultrasonic energy under conditions suitable to chemically associate the carbonaceous material with a short chain organic molecule to generate a carbonaceous material having a chemically associated functional group (e.g., o-SAC).
  • the carbonaceous material having a chemically-associated functional group may retain greater than about 85% of the original pore morphology of the carbonaceous material.
  • the carbonaceous material having a chemically associated functional group may retain within about 10% of the original porosity of the carbonaceous material.
  • generation of the carbonaceous material having a chemically associated functional group results in the generation of microparticles (e.g., fines) that constitute less than about 1.0 wt.% of the original weight of the carbonaceous material, alternatively less than about 0.5 wt.%), less than about 0.4 wt.%, less than about 0.3 wt.%, less than about 0.2 wt.% or less than about 0.1 wt.%).
  • the carbonaceous material having a chemically associated functional group is prepared from a carbonaceous material that contains from about 80 wt. %> to about 100 wt. %> chemically pure carbon.
  • the carbonaceous material may contain additional elements as H, N, O, S, P and combinations thereof.
  • a method of the present disclosure further comprises modification of the chemically associated functional group to produce a chemical moiety available to interact with one or more user and/or process desired disease-related toxins.
  • the carbonaceous material having a chemically-associated functional group may be a component of a therapeutic process for the treatment of a medical condition.
  • the carbonaceous material having a chemically-associated functional group may be characterized as a material that associates with disease-related toxins but exhibits minimal shedding of particulates (e.g., microfines) when contacted with one or more bodily fluids.
  • the SACs disclosed herein may be prepared to contain of macropores having pores 0.05 ⁇ to 1.0 ⁇ in effective diameter.
  • the SACs may be prepared by attaching short chain organic molecules and further attaching therapeutic substances to the structure.
  • therapeutically selected active substances may be permanently attached to or associated with the SAC through short chain molecular anchors. Such attachments and/or associations may be made after formation of and characterization of the pore structure of the carbonaceous material.
  • the therapeutic substances attached to short chain molecular anchors can have positive, negative or nearly neutral electric charges.
  • the carbonaceous material having a chemically-associated functional group may be characterized by a dramatic increase in effective treatment surface area when compared to the original carbonaceous material. Further, carbonaceous material having a chemically-associated functional group of the type disclosed herein (i.e., SAC) may display a reduced amount of shedding of microparticles from macropore walls during handling, assembly, and interaction with bodily liquids.
  • the carbonaceous material having a chemically-associated functional group may be further characterized by a structure containing a plurality of pore sizes such as macro-, meso-, and micro- pores where the mesoporous integral porosity is smaller than or equal to the macroporous integral porosity.
  • the carbonaceous material having a chemically-associated functional group i.e., SAC
  • the chemically-associated functional group may be subjected to further modifications (e.g., oxidation) to improve the selectivity of disease-related toxin removal from bodily liquids.
  • a selectively adsorbent carbon material of the type disclosed herein was prepared. Chemicals used in ultrasonic experiment are following PEG 300, PEG 2000, PEG 60000 which were used as purchased from Sigma Aldrich. PEG 60000 was used as calibrated marker for rheological properties pre and after sonication solutions. Sonication solutions had 5%, 10%, 15%, 20%, and 25% of polymer by weight in deionized and debased water under constant temperature of 25 °C. Sonications were performed in sonication baths with variable sonication frequency and intensity manufactured by EMYSONIC 310 GmHB utilizing a variable intensity sonication probe operating at 25 kHz.
  • FIGS. 2 and 3 are plots of the covalent bonding (indicated by FTIR spectra) observed in solution as a function of ultrasonic frequency utilized (kHz, Figure 2) or ultrasonic power (W, Figure 3).
  • Exemplary aspects of the present disclosure include the following non-limiting aspects.
  • a first aspect which is a carbonaceous material comprising at least 80 wt. % pure carbon and a functional group, wherein the functional group has been chemically-associated with the carbonaceous material by ultrasonication.
  • a second aspect which is the carbonaceous material of the first aspect wherein the functional group has a molecular weight of equal to or less than about 1000 g/mole.
  • a third aspect which is the functional group of any of the first through second aspects wherein the functional group comprises a heteroatom.
  • a fourth aspect which is the functional group of any of the first through third aspects wherein the functional group comprises an unsaturation.
  • a fifth aspect which is the carbonaceous material of any of the first through fourth aspects wherein the functional group comprises organic acids, organic amides, organic amines, organic esters, organic anhydrides, organic alcohols, organic acid halides (such as acid chlorides, acid bromides, etc.) organic peroxides, unsaturated carboxylic acids, esters of the unsaturated carboxylic acids, acid anhydrides, di-esters, salts, amides, imides, aromatic vinyl compounds hydrolyzable unsaturated silane compounds and unsaturated halogenated hydrocarbons.
  • the functional group comprises organic acids, organic amides, organic amines, organic esters, organic anhydrides, organic alcohols, organic acid halides (such as acid chlorides, acid bromides, etc.) organic peroxides, unsaturated carboxylic acids, esters of the unsaturated carboxylic acids, acid anhydrides, di-esters, salts, amides, imides, aromatic vinyl compounds hydrolyzable unsaturated silane compounds and uns
  • a sixth aspect which is the carbonaceous material of any of the first through fifth aspects wherein the functional group comprises maieic anhydride, citraconic anhydride, 2-methy] maleic anhydride, 2-ch!oromaleic anhydride, 2,3-dimethylmaleic anhydride, bicyclo[2.2.1]-5-heptene-2,3- dicarboxylic anhydride and 4-meth.yl-4-cyc3ohexene-l,2-dicarboxylic anhydride, acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, citraconic acid, mesaconic acid, crotonic acid, bicycio[2.2.2]oct-5-ene-2,3-dicarboxylic acid anhydride, 1,2,3,4,5,8,9, 10- octahydronaphthalene-2,3-dicarboxylic acid anhydride, 2-oxa-l,3-diketospiro[
  • a seventh aspect which is the carbonaceous material of any of the first through sixth aspects wherein the functional group comprises methyl acrylate, ethyl acrylate, butyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate or combinations thereof.
  • An eighth aspect which is the carbonaceous material of any of the first through seventh aspects having equal to or greater than about 10% of the original porosity of the carbonaceous material.
  • a ninth aspect which is the carbonaceous material of any of the first through eighth aspects having less than about 1.0 wt.% of microparticles based on the original weight of the carbonaceous material.
  • a tenth aspect which is the carbonaceous material of any of the first through ninth aspects having macropores ranging in size from about 0.05 ⁇ to about 1.0 ⁇ in effective diameter.
  • An eleventh aspect which is the carbonaceous material of any of the first through tenth aspects wherein the functional group comprises a polymerizable monomer.
  • a twelfth aspect which is the carbonaceous material of the eleventh aspect wherein the monomer comprises ethylene, ethylene glycol, propylene, acrylates, methyl methacrylate, n-butyl acrylate, vinyl acetates, acrylamide, ethylene oxide, or combinations thereof.
  • a thirteenth aspect which is the carbonaceous material of any of the first through fourth aspects wherein the functional group comprises an oligomer or polymer.
  • a fourteenth aspect which is the carbonaceous material of the thirteenth aspect wherein the functional group comprises greater than about 80 wt. % oligomer.
  • a fifteenth aspect which is a method comprising obtaining an uncleansed bodily fluid from a subject; contacting the uncleansed bodily fluid with a carbonaceous material comprising at least 80 wt. % pure carbon and a functional group, wherein the functional group has been chemically-associated with the carbonaceous material by ultrasonication; obtaining a cleansed bodily fluid subsequent to the contacting; and recovering the cleansed bodily fluid.
  • a sixteenth aspect which is the method of the fifteenth aspect wherein the uncleansed bodily fluid comprises whole blood, diluted blood, heparinized blood, plasma, frozen plasma, cerebral liquid, or combinations thereof.
  • a seventeenth aspect which is the method of any of the fifteenth through sixteenth aspects wherein the uncleansed bodily fluid comprises disease mediators.
  • An eighteenth aspect which is the method of the seventeenth aspect wherein the disease mediators comprise nitric oxide, nitrogen dioxide, nitrate, hydrogen peroxide; billirubin, cretinine, heme; LPS-endotoxin; vascular endothelia growth factor, epidermal cell-derived factor, fibroblast growth factor, nerve growth factor, growth-regulated protein alpha, Interferon-inducible T-cell alpha chemoattractant, stem cell factor, transforming growth factor beta; C-reactive protein, transforming growth factor-alpha, interleukin 1-beta; interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin 12, interleukin- 17; cholesterol, high-density lipoproteins, low-density lipoproteins, very low-density lipoproteins, triglycerides; liver enzymes, alanine transaminase, aspartate transaminase,
  • a nineteenth aspect which is the method of any of the seventeenth through eighteenth aspects wherein the disease mediators are present in the uncleansed bodily fluid in an amount designated x and the disease mediators are present in the cleansed bodily fluid in an amount designated y.
  • a twentieth aspect which is the method of the nineteenth aspect wherein y has a value that is that is from about 10% to about 90% less than x.
  • a twenty-first aspect which is the method of any of the fifteenth through twentieth aspects wherein the subject is experiencing systemic inflammatory response syndrome.
  • a twenty-second aspect which is the method of any of the fifteenth through twenty- first aspects wherein the subject is experiencing chronic kidney disease.
  • a twenty-third aspect which is the method of any of the fifteenth through twenty- second aspects wherein the subject is experiencing hepatic encephalopathy.

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Abstract

La présente invention concerne un matériau carboné comprenant au moins 80% en poids de carbone pur et un groupe fonctionnel, le groupe fonctionnel ayant été chimiquement associé à la matière carbonée par traitement aux ultrasons. En outre, l'invention concerne un procédé comprenant l'obtention d'un fluide corporel non purifié prélevé sur un patient; la mise en contact du fluide corporel non purifié avec un matériau carboné comprenant au moins 80% en poids de carbone pur et un groupe fonctionnel, le groupe fonctionnel ayant été chimiquement associé à la matière carbonée par traitement aux ultrasons; l'obtention d'un fluide corporel purifié après la mise en contact; et la récupération du fluide corporel purifié.
PCT/US2017/025570 2016-03-31 2017-03-31 Adsorbant sélectif de médiateurs de maladie WO2017173382A1 (fr)

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