United States Patent 19
`Mueller
`
`11)
`45)
`
`4,094,775
`June 13, 1978
`
`(54) DIALYSIS SYSTEM
`75 Inventor: William A. Mueller, Glendale, Calif.
`73) Assignee: California Institute of Technology,
`Pasadena, Calif.
`21 Appl. No.: 772,434
`22 Filed:
`Feb. 28, 1977
`51
`int. Cl’.............................................. B01D 13/00
`52 U.S. C. ................................... 210/22; 210/321 B
`58) Field of Search ........................ 210/22, 23, 321 B
`(56)
`References Cited
`U.S. PATENT DOCUMENTS
`... 210/321
`9/1971 Haselden.
`3,608,729
`3,617,545 11/1971
`Dubois ............
`. 210/22
`3,669,880
`6/1972 Marantz et al. .
`210/22
`o
`3,703,959 11/1972 Raymond ............................. 210/321
`
`3,994,799 11/1976 Yao et al. ........................ 210/321 A
`Primary Examiner-Charles N. Hart
`Assistant Examiner-E. Rollins Cross
`Attorney, Agent, or Firm-Marvin E. Jacobs
`57
`ABSTRACT
`The improved hemodialysis system utilizes a second
`polymeric membrane having dialyzate in contact with
`one surface and a urea decomposition solution in
`contact with the other surface. The membrane selec
`tively passes urea from the dialyzate into the decompo
`sition solution, while preventing passage of positively
`charged metal ions from the dialyzate into the solution
`and ammonium ions from the solution into the dialy
`Zate.
`
`19 Claims, 4 Drawing Figures
`
`
`
`
`
`SPENT
`DALYZATE
`
`
`
`22
`
`PURIFED
`DALYZATE
`
`GCE - Exhibit 1022, Page 1
`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
`
`

`

`U.S. Patent
`
`June 13, 1978
`
`4,094,775
`
`8
`
`2
`
`+ UREASE
`
`
`
`NH
`4
`--
`HC0;
`
`
`
`
`
`
`
`20
`
`-n.
`SPENT
`DALYZATE
`
`
`
`PURI FED
`DALYZATE
`
`ARTERIAL
`BLOOD
`
`A. 27- 4
`
`
`
`
`
`F-86
`TO VEN
`
`GCE - Exhibit 1022, Page 2
`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
`
`

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`1.
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`O
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`
`DALYSES SYSTEM
`ORIGIN OF THE INVENTION
`The invention described herein was made in the per
`formance of work under a NASA contract and is sub
`ject to the provisions of Section 305 of the National
`Aeronautics and Space Act of 1958, Public Law 83-568
`(72 Stat. 435; 42 USC 2457).
`BACKGROUND OF THE INVENTION
`1. Field of the Invention
`The present invention relates to a hemodialysis sys
`tem and, more particularly, to an improved system for
`selectively removing urea from dialyzate.
`2. Description of the Prior Art
`A sizable fraction of the estimated 50,000 people who
`die of kidney failure each year in the United States are
`free of other complications and might be restored to
`20
`useful life if their kidney function could be provided
`artificially. At present, artificial kidneys (using hemodi
`alysis) and clinical procedures have been developed to
`the point where long-term sustenance of life by periodic
`hemodialysis is practical in many cases.
`The limitations in using hemodialysis are the small
`number of patients who can be treated with a given
`kidney machine and the considerable expense of main
`taining and staffing a kidney-treatment center. Obvi
`ously, a desirable solution lies in the development of an
`30
`artificial kidney which is inexpensive, portable and ca
`pable of being operated outside the confines of a hospi
`tal with a minimum of medical attention. Attainment of
`this solution will require increased efficiency of mass
`transfer and further optimization in design of artificial
`35
`kidney systems.
`In recent years, considerable attention has been fo
`cused on methods of reducing the size of the artificial
`kidney. This requires miniaturization of the membrane
`containing dialyzer and a significant reduction in the
`volume of dialyzing fluid. It is generally conceded that
`the toxin primarily responsible for the uremic syndrome
`has not yet been identified. Even though urea is not
`considered particularly toxic, its removal is one of the
`chief objectives of dialysis as practiced today. The rea
`45
`son for the concentration on urea removal is that, in the
`absence of more specific knowledge, dialysis based on
`this principle is obviously beneficial. At least two expla
`nations suggest themselves: (a) Unidentified toxicants
`are removed along with the urea. (b) Urea produces
`toxic products.
`In order to increase the efficiency of hemodialysis, it
`is desirable to maintain the trans-membrane concentra
`tion gradient of waste metabolites as high as possible.
`Low waste concentrations in the dialyzing fluid have in
`55
`the past been maintained by two methods. The more
`widely used method is the continual dilution of the
`dialyzed substances in a large reservoir of fluid, usually
`100 to 300 liters. A second method of maintaining the
`gradient is to use the dialyzing fluid in a single-pass
`operation, where the waste-bearing effluent is dis
`carded. Even then, more than 100 liters of fluid are
`required. The current research trend in obtaining low
`concentrations of wastes is to remove them selectively
`from the dialyzing fluid. Such an approach would allow
`65
`the use of much smaller volumes of dialyzing fluid.
`Among all waste products, urea is by far the major
`waste metabolite which must be removed daily from the
`
`4,094,775
`2
`body fluid. Three major methods of urea removal from
`dialysate have been reported.
`The first procedure utilizes an activated carbon bed
`which removes urea by absorption. However, the dem
`onstrated capacity for urea is only 0.2-0.8 grams per 100
`grams of carbon. In another method urea is reduced by
`enzymatic hydrolysis either inside microcapsules or by
`the combination with other absorbents. However, enzy
`matic decomposition of urea produces large concentra
`tions of ammonium ion which is toxic. Therefore, it is
`essential to achieve rapidly removal of the ammonium
`ion or it can accumulate in the dialyzate and enter the
`blood. A commercial apparatus utilizes sodium zirco
`nium phosphate to remove the ammonia produced by
`enzymatic decomposition of urea in the presence of
`urease. Though this system does remove urea from
`dialyzate it also removes essential metal ions such as
`strontium and calcium which must be replaced. Fur
`thermore, large amounts of zirconium phosphate are
`required and the process is expensive since the spent
`zirconium phosphate absorbent is not regeneratable and
`must be discarded.
`SUMMARY OF THE INVENTION
`The improved hemodialysis system in accordance
`with the invention obviates the need for an ammonia
`absorbent in the urea decomposition solution. The sys
`tem of the invention permits purification and recircula
`tion of dialyzate fluid in an efficient manner and sub
`stantially reduces the quantity of dialyzate needed for
`dialysis making it feasible to produce a portable, or
`wearable artificial kidney system. The degradation
`products produced by the dialyzate treating portion of
`the apparatus forms a soluble toxic component and a
`soluble nontoxic component. The toxic component is
`retained in the treating section of the apparatus while
`the nontoxic component may migrate or diffuse back
`into the dialyzate for safe elimination in the body of the
`patient. The system of the invention also prevents diffu
`sion of essential metal ions from dialyzate into the treat
`ing solution.
`Urea is continuously removed from dialyzate in ac
`cordance with the invention by passing the urea in
`contact with a polymeric membrane selectively perme
`able to urea. The urea passes through the membrane
`into a solution containing a urea decomposition agent
`such as the enzyme urease. The urea is decomposed into
`ammonium and bicarbonate ions. The membrane is
`selectively impermeable to ammonium ion but may pass
`the bicarbonate back into dialyzate and eventually
`through the primary membrane into the blood. How
`ever, bicarbonate is nontoxic and is readily decomposed
`and eliminated by exhalation as carbon dioxide. The
`membrane used in the dialyzate purification section is
`also selectively nonpermeable to essential positive cati
`ons such as strontium and calcium which remain in the
`dialyzate obviating the need to replenish these metals as
`is practiced in commercial systems. Preferred mem
`branes are positively charged membranes, suitably poly
`quaternary substituted cation exchange resins, since
`such membranes do not require gradient effects for
`providing the desired nonselectivity to passage of cati
`ons in either direction.
`The dialyzate treating apparatus of the invention has
`demonstrated the capability of removing almost half the
`urea content of test dialyzates in 20 hours while retain
`ing up to about 90% ammonium ions in the treating
`chamber. Operation is continuous and regeneration
`
`25
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`50
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`GCE - Exhibit 1022, Page 3
`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
`
`

`

`5
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`15
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`25
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`4,094,775
`3
`4.
`simply involves replacing the low cost urease enzyme.
`of urea in the dialyzate. Usually the urea concentration
`The system substantially reduces the amount of dialy
`should be at least 25-300% the concentration of the
`urea in the dialyzate in order to provide adequate peri
`Zate required and a small size is indicated for use in
`ods before the need to recharge urease to the treating
`current clinical dialyzers in a typical thrice weekly
`dialysis regimen.
`chamber.
`The dialyzate treating unit of the invention can be
`These and many other features and attendant advan
`combined with many diverse types of hemodialysis
`tages of the invention will become apparent as the in
`units. In its simplest form shown in FIG. 2 the dialyzate
`vention becomes better understood by reference to the
`following detailed description when considered in con
`chamber 24 would have one wall formed by the pri
`junction with the accompanying drawings.
`mary membrane 26 and another wall portion formed of
`O
`the secondary treating membrane 28. Blood from an
`BRIEF DESCRIPTION OF THE DRAWINGS
`artery enters the inlet 30 to continuous flow through
`chamber 32 and leaves through outlet 34. As the blood
`FIG. 1 is a schematic illustration of a spent dialyzate
`flows past primary membrane 26 such as a cellulose
`urea removal unit in accordance with the invention;
`ester, preferably a cupprammonium treated cellulose
`FIG. 2 is a schematic illustration of an artificial kid
`ney hemodialysis unit incorporating the dialyzate treat
`acetate, urea diffuses through membrane 26 into the
`dialyzate chamber 24. The urea in turn will diffuse
`ing unit of the invention;
`through secondary positively charged membrane 28
`FIG. 3 is a schematic illustration of a hollow fiber
`into the treating section 36 where it will be decomposed
`hemodialysis apparatus in accordance with the inven
`by urease into ammonium and bicarbonate ions. The
`tion; and
`20
`bicarbonate ions will build up in concentration and can
`FIG. 4 is a schematic illustration of an artificial kid
`ney machine incorporating a single cationic membrane
`flow backwards through membrane 28 into the dialy
`and having the urease present in the dialyzate,
`zate and in turn through membrane 26 into the blood.
`The blood will leave through outlet 34 and will be
`DESCRIPTION OF THE PREFERRED
`returned to a vein of the subject by intravenous injec
`EMBODIMIENTS
`tion.
`In the typical artificial kidney machine a very thin
`Referring now to FIG. 1 the dialyzate treating unit 10
`film of flowing blood is separated from the surrounding
`of the invention includes a container 12 divided into a
`dialyzate solution by an approximately 3 mill thick semi
`dialyzate chamber 14 and a urea decomposition cham
`ber 16 by a common membrane 18. Spent dialyzate
`permeable cellulose acetate membrane. This membrane
`30
`enters chamber 14 through inlet 20 and purified dialy
`allows substances in normal molecular solution and the
`solvent to pass through its pores but it prevents the
`zate leaves through outlet 22. The membrane 18 is per
`passage of very large molecules such as proteins and
`meable to the urea which diffuses into chamber 16
`which contains a solution of urease enzyme. The en
`cellular constituents of the blood. The membrane does
`zyme decomposes the urea into ammonium ion which is
`not permit the passage of bacteria and viruses so that
`35
`repelled by the membrane 18 and is retained in chamber
`sterilization of the apparatus located outside the mem
`brane is not required. Since the apparatus operates by
`14 and into bicarbonate which may permeate through
`the membrane 18 into the dialyzate. The purified dialy
`diffusion and osmosis the dialyzate liquid must contain
`physiological concentrations of all membrane-passing,
`zate may be recycled to the dialysis section of a hemodi
`alysis unit.
`dissolved normal constituents of the blood, electrolytes
`in particular, which are required to be maintained in the
`The membrane 18 is formed of a high molecular
`weight synthetic polymer having good tensile strength,
`blood. The dialyzate may also contain high concentra
`elongation and flexural strength. The membrane is se
`tions of substances which it is desired to introduce into
`lectively permeable to solvated urea molecules while
`the blood stream by diffusion such as drugs, dextrose,
`preventing passage of larger molecules and preventing
`etc. The dialyzate must be at the same temperature as
`45
`the blood this usually being effected by thermostatic
`passage of cationic ammonium or metallic ions in either
`control. Oxygen may be bubbled into the dialyzate so as
`direction. Preferred membrane materials are synthetic
`polymers containing cationic groups such as phospho
`to maintain the oxygen content of blood in a normal
`nium, sulfonium or quaternary nitrogen. A suitable
`condition. The kidney machine may also contain a
`pump and means to introduce anticoagulants such as
`membrane material is RAI P-4025 which is a polyethyl
`50
`ene containing 45% grafted vinylpyridine having an
`hirudin or heparin into the blood to prevent clotting of
`ion-exchange capacity of 5 meq/gm and a resistance of
`the blood on all surfaces of the apparatus that are in
`1 ohm-cm. The membrane may be utilized in various
`contact with blood.
`A principle requirement of a kidney machine is that
`thicknesses depending on the desired flow rate and
`mechanical properties required in the purification unit.
`the semipermeable membrane should have a large sur
`55
`face area to insure adequate osmotic interchange be
`The thickness may be from 1-15 mill, generally around
`tween the blood and the dialyzate. This usually requires
`2-10 mill in thickness. The surface area membrane is
`selected so as to give adequate removal of urea from the
`that the blood flow in a verythin film to provide maxi
`dialyzate. From experiments to date, it is estimated that
`mum contact with the membrane bathed by the dialy
`Zate liquid. Many configurations of kidney machines
`the surface required would be about 10 to 40 square
`have been devised and are all compatible with the dialy
`inches.
`The treating chamber 16 should contain concentra
`Zate treating section or unit of the invention. The blood
`dialyzate portion of the equipment may be in the form
`tions of low molecular weight ingredients equal to that
`contained in the dialyzate chamber 14. For example,
`of a rotary drum apparatus in which a blood-filled flat
`cellophane tube is wound in helical fashion around a
`buffer concentration should be equivalent as should
`rotating drum made of wire mesh, the drum being
`saline concentration to prevent diffusion from dialyzate
`bathed or submerged in dialyzate. A sandwich-type
`into the treating solution. The urease concentration
`apparatus has been devised and can more readily be
`should be sufficient to significantly decrease the amount
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`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
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`4,094,775
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`6
`utilized for ultrafiltration under pressure. In this form of
`can be replaced as needed. Should the hollow fibers of
`construction a flat cellophane bag is sandwiched be
`the blood cartridge 68 become damaged or worn out,
`tween grooved plates of plastic. The dialyzate liquid
`that unit can be replaced. Any of the cartridges can be
`flows through the grooves in the opposite direction to
`readily removed for sterilization.
`the flow of blood in the cellophane bag. However, this
`An example of practice follows.
`configuration provides dead flow spaces providing an
`Two cylindrical chambers of about 30 mls. capacity
`inherent danger of clotting unless large amounts of
`were separated by a positively charged membrane (RAI
`anticoagulants are used. Another configuration is a
`P-4025 membrane) having a surface area of about one
`twin-coil apparatus in which the semipermeable mem
`square inch. Synthetic test solutions were introduced on
`brane is in the form of a flat, wide cellophane tube
`each side of the membrane. The synthetic dialyzate
`10
`which is coiled in two tiers around the hollow core. The
`contained about 2 gm/liter of urea, 4.5 gm/liter of so
`coils are mounted inside a container through which the
`dium acetate trihydrate and 5.8 gm/liter of sodium
`rinsing liquid is passed. A very thin film of blood flows
`chloride. The urease chamber test solution contained
`through the coils which present a large area of contact
`about 1 gm/liter of urease, 4.5gm/liter sodium acetate
`with the surrounding liquid. This has the advantage that
`trihydrate and 5.8 gm/liter of sodium chloride.
`the modules can be supplied, sterilized and ready to use
`After six hours analysis showed that the quantity of
`inside the container and can be quickly and easily ex
`urea in dialyzate had dropped about 25% and that sig
`changed.
`nificant concentrations of ammonium were present in
`Hollow fibers also offer the advantage of high surface
`the urease chamber. After 20 hours, urea concentration
`area in a very compact volume. Hollow fibers may be
`had dropped 45% and about 90% of the ammonia was
`utilized for either or both of the membranes discussed
`present in the urease chamber, but the urease chamber
`herein. A more complete artificial kidney machine em
`now is found to contain no urea.
`ploying hollow fibers is illustrated in FIG. 3. In the
`The above experiment demonstrates that urea readily
`kidney machine 40 of FIG. 3 a cylindrical container 42
`diffuses through the membrane and is rapidly hydro
`houses the dialyzate chamber 44. The container 42 is
`lyzed to ammonium bicarbonate. The initial rate of
`25
`surrounded with a heating jacket 46 such as an electric
`removal of urea from dialyzate was about 0.1 gm/hr
`resistance heater powered by thermostatically con
`and about 0.05 gm/hr after 20 hours for the 4-5 mil
`trolled power unit 48. The cellulose acetate membrane
`thick film utilized. Higher diffusion rates can be ex
`is in the form of a plurality of fine filamentary hollow
`pected with thinner membranes. The positively charged
`fibers 50 having their inlet ends potted to a common
`membrane also demonstrated the ability to isolate the
`30
`toxic ammonium ion from the dialyzate and to retain the
`inlet header 52 and their outlet ends connected to a
`essential metal cations within the dialyzate. Preliminary
`common outlet header 54. Each of the headers 52 and
`54 can be threadingly and sealingly received into the
`estimates indicate that the dialyzate membrane need
`only require 24 in of surface area to be compatible with
`side walls 56, 58 of the container 42.
`the urea production of conventional hemodialysis units.
`The second membrane may also be in the form of a
`A cartridge or treating chamber could readily be
`plurality of hollow fiber tubes containing the urease
`solution and connected to the common inlet and outlet
`housed in a 1 ft. X 2 in. X 2 in. unit which is well within
`design constraints for continuous operation in portable
`headers as in the blood chamber described above. How
`or wearable artificial kidney apparatus for a typical
`ever, since there is no need to recirculate the urease
`thrice weekly dialysis regimen. Urease enzyme is not
`solution the dialyzate treating chamber can be in the
`expensive and can readily be recharged for the next
`form of a cartridge 60 in which the plurality of hollow
`dialysis treatment.
`fibers 62 have both ends connected to a base 62 which
`is threadingly received into a wall 58 of the container
`The urease solution could be pumped past the mem
`42. A further replaceable cartridge element 64 may be
`brane and removed from the chamber for continuous
`provided in the chamber containing an effective absor
`replenishment of urease and removal of ammonium
`45
`ions. Similarly the dialyzate could be continuously
`bent such as activated carbon to remove other impuri
`ties from the dialyzate.
`pumped in concurrent or countercurrent flow past both
`The kidney machine 40 of FIG. 3 is utilized by filling
`membranes to increase urea transfer rate from the blood
`the chamber 44 with dialyzate through inlet plug 66.
`into the dialyzate. Another configuration would be to
`encapsulate the urease within a positively charged poly
`The absorbent cartridge 64, dialyzate treating cartridge
`60 and blood cartridge 68 are inserted. The heater 48 is
`meric membrane and place the capsules in-line in the
`dialyzate flow path to absorb urea from the dialyzate
`turned on and a first catheter 70 is inserted into a vein of
`while retaining ammonium salts within the capsules.
`the subject and connected to blood outlet 72 and a sec
`ond catheter 74 is inserted into an artery of the subject
`The cationic polymer membrane can also be utilized
`and connected to the pump 76. The pump is then ener
`to form a single membrane, low dialyzate volume arti
`gized and as blood is drawn from the artery and
`ficial kidney machine. Referring now to FIG. 4, the
`through the hollow fiber tubes 50 of the blood car
`machine 70 includes a container 72 divided into a blood
`tridge, urea passes into the common body of dialyzate
`chamber 74 and a dialyzate chamber 76 by means of a
`44 and then through the walls of hollow fiber tubes 62
`cationic membrane 78. The membrane 78 repels and
`of the cartridge 60 where urea is decomposed and re
`prevents passage of NH4+ ions 80 and M ions 82.
`Therefore the dialyzate need not contain equilibrium
`tained therein. However, the positively charged walls
`of the hollow fibers 62 prevent the ammonium ions
`concentrations of the essential cations such as strontium
`from entering the dialyzate and prevent metal cations
`or calcium.
`from the dialyzate from entering the tubes 62. Other
`The blood chamber 74 contains an inlet 84 and an
`impurities are absorbed onto the granules 78 of acti
`outlet 86. As the blood flows past the membrane 78,
`essential large proteins, cellular constituents and cations
`vated carbon within the cartridge 64. As the urease
`containing cartridge 60 is exhausted a new cartridge is
`are retained in the blood, while urea 88 traverses the
`inserted. Similarly, the activated carbon cartridge 64
`membrane 78, enters the dialyzate chamber 76 and is
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`GCE - Exhibit 1022, Page 5
`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
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`4,094,775
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`10. A method of selectively removing urea from an
`decomposed into NH and HCO. The ammonium
`aqueous liquid containing urea and positive metal cati
`ion is retained in the dialyzate chamber. Substantially
`ons comprising the steps of:
`smaller amounts of dialyzate are required compared to
`placing the liquid in contact with a first surface of a
`dilution and continuous flowing dialyzate configura
`cationically charged polymeric membrane selec
`tions.
`tively permeable to urea and having low permea
`It is to be realized that only preferred embodiments of
`bility to cations;
`the invention have been described and that numerous
`placing an urea decomposition solution containing an
`Substitutions, modifications and alterations are permissi
`urea decomposition agent in contact with a second
`ble without departing from the spirit and scope of the
`surface of the membrane; and
`invention as defined in the following claims.
`selectively permeating urea from the liquid through
`What is claimed is:
`the membrane into the solution thereby decompos
`1. A system for selectively removing urea from an
`ing urea into ammonium cations and bicarbonate
`aqueous liquid containing urea and positive metal cati
`whereby the ammonium cations are retained in the
`ons comprising in combination:
`decomposition solution and the metal cations are
`a container divided into a first chamber and a second
`retained in the liquid.
`chamber by means of a continuous sheet of cationi
`11. A method according to claim 10 in which the
`cally charged polymeric membrane selectively
`membrane contains quaternary ammonium groups.
`permeable to urea and having low permeability to
`12. A method according to claim 11 in which the
`cations;
`membrane has an exchange capacity of from 1 to 20
`said first chamber including means for receiving said
`meg/gm.
`liquid; and
`13. A method according to claim 12 in which the
`said second chamber receiving a solution containing a
`membrane is a vinyl pyridine grafted polyethylene hav
`urea decomposition agent whereby said cations are
`ing a thickness from 1 to 15 mils.
`repelled by said membrane and retained in said
`14. A method according to claim 11 in which the
`25
`liquid and urea permeates through the membrane
`agent is urease.
`into the solution and is decomposed into bicarbon
`15. A method according to claim 14 in which the
`ate and ammonium, the ammonium being retained
`urease concentration of the decomposition solution is at
`in the solution in the second chamber.
`least 25% of the concentration of urea in the urea con
`2. A system according to claim 1 in which the mem
`taining liquid.
`30
`brane contains quaternary ammonium groups.
`16. A method according to claim 14 in which the urea
`3. A system according to claim 2 in which the mem
`containing liquid is dialyzate from a blood dialysis unit.
`brane is a vinyl pyridine grafted polyethylene.
`17. A method according to claim 14 in which the urea
`4. A system according to claim 1 in which the mem
`containing liquid is blood.
`brane has a thickness from 1 to 15 mils.
`18. An artificial kidney machine comprising in combi
`35
`5. A system according to claim 4 in which the mem
`nation:
`brane has an exchange capacity of 1 to 20 meq/gm.
`enclosure means having an inlet and an outlet, and
`6. A system according to claim 1 in which the first
`having a wall surface formed of a cationically
`chamber is a hollow body having said membrane as one
`charged membrane defining a channel for flowing
`wall thereof and having an inlet and outlet for flowing
`urea containing blood past one surface of the mem
`40
`said liquid past a first surface of the membrane.
`brane;
`7. A system according to claim 1 in which the urea
`urea removal means comprising walls defining a
`decomposition agent is urease.
`chamber, said chamber including a solution of ure
`8. A system according to claim 7 in which the urease
`ase having a concentration at least 25% by weight
`concentration of the solution is at least 25% by weight
`of the urea content of the blood; and
`45
`of the urea content of the liquid.
`means for supplying the urea permeate from the sec
`9. A system according to claim 7 in which the liquid
`ond surface of the membrane to the urease solution.
`is dialyzate containing urea and further including a
`19. A machine according to claim 18 in which the
`blood dialysis membrane selectively permeable to urea
`membrane forms a common wall portion of said channel
`having one surface in contact with said dialyzate and a
`and chamber.
`50
`second surface for contacting a flow of blood.
`
`2
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`GCE - Exhibit 1022, Page 6
`GCE Gas Control Equipment Inc. v. VBOX, Inc.
`IPR2023-00326
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