Urea sorbent

Information

  • Patent Grant
  • 8672145
  • Patent Number
    8,672,145
  • Date Filed
    Monday, July 29, 2013
    10 years ago
  • Date Issued
    Tuesday, March 18, 2014
    10 years ago
Abstract
A sorbent polymer is provided that interacts or reacts with aqueous urea to aid the regeneration of a dialysate liquid. The sorbent polymer may include one or more specific functional groups bonded thereto. Such specific functional groups are selected from carboxylic acids, carboxylic acid esters, carboxylates, amides, dicarboxylic acids, dicarboxylic acid esters, and dicer boxylates to produce the desired urea sorbent.
Description
TECHNICAL FIELD

The following disclosure relates to sorbent materials for separating and/or removing urea from dialysate solutions in sorbent-based dialysis treatment or for separating and/or removing urea from aqueous solutions or liquids in medical related processes or circumstances.


BACKGROUND

Hemodialysis is a process by which toxins and other molecules, such as urea, are removed from the blood using a semi-permeable filtering membrane. Typically, the patient's blood and an aqueous solution (i.e., dialysate) are pumped in counter-direction flows in and about hollow, semi-permeable fibers. In FIG. 1 a known configuration of a dialyzer is shown. Generally, blood flows in one end of the dialyzer and through hollow semi-porous or semipermeable fibers toward the blood output side of the dialyzer. Meanwhile, dialysate flows in an opposite direction, with respect to the blood flow, by entering a dialysate inlet and flowing around or about the semi-porous hollow fibers in which the blood is flowing. The dialysate then exits the dialysate outlet. The toxins within the blood are removed from the blood via a combination of diffusion, convection, and osmosis processes while the blood is flowing within the fibers and the dialysate is flowing outside the fibers. Generally, the dialyzer is comprised of a large number of semi-permeable hollow fibers bundled together and placed in a cylindrical jacket as shown. Present day dialysis processes may be classified as: 1) single pass; and 2) sorbent-based. Single pass processes require a continuous supply of gallons of fresh and treated water. The treated water may be purified by for example, reverse osmosis or distillation. The gallons of fresh and treated water are used to create the dialysis fluid, which is discarded after flowing through the dialyzer and collecting the toxins in a single pass through of the dialyzer.



FIG. 2 shows a schematic/diagram of a cross section of a single semi-permeable fiber that may be used in a dialyzer. The blood flows through the hollow lumen within the semi-permeable walls of the fiber. The membrane walls have a thickness, which is the difference of the radius R2 minus the radius R1. The membrane is semi-permeable and the dialysate, as shown, flows in the opposite direction outside of the semi-permeable fiber.


Sorbent dialysis differs from single pass dialysis in that the dialysate is regenerated using a series of chemical powders to remove toxins from the dialysate solution. Typically, spent dialysate from the dialyzer is pumped through the first chemical layer of an enzyme called “urease”. The urease catalyzes the breakdown of urea into ammonia and carbon dioxide. The dialysate will then pass through a second chemical layer, a cation exchange layer (zirconium phosphate) which absorbs ammonia and other positively charged ions and then through a third, chemical layer, an anion exchange layer (hydrous zirconium oxide) where anions such as phosphate and fluoride are absorbed. Finally, the dialysate is pumped through a fourth layer of activated carbon where organic metabolites such as creatinine are absorbed. At some point, the filtered dialysate may be passed through a degasser to remove air, carbon dioxide and other gas bubbles that may form or be found in the dialysate.


The capacity of the zirconium phosphate cation exchange layer to absorb ammonia is limited by the number of sites available to bind ammonia. If the zirconium phosphate layer is depleted, ammonia will remain in the dialysate as it is recycled to the dialyzer. In this case the patient may be at risk of ammonia toxicity. Consequently, the filtered dialysate must be periodically tested or monitored for ammonia concentration.


A typical dialysis patient generates an excess of about 24 to about 60 grams of urea per day that must be removed from the blood to avoid uremia. Therefore, what is needed is a sorbent for use in dialysis that has the capacity to remove this quantity of urea in a reasonable time frame. Thus, suitable sorbents should have the capacity to remove approximately 2.5 grams per deciliter of dialysate per hour (gm/dl/hr) from the dialysate.


SUMMARY

In one embodiment, a urea sorbent is provided that is suitable for use in a sorbent-based dialysis process. The sorbent absorbs urea from the dialysate without generating ammonia or carbon dioxide, thereby eliminating the need for monitoring the concentration of ammonia in the dialysate as well as reducing or eliminating the need for de-gassing the dialysate. In one variation, the sorbent is insoluble or substantially insoluble in water and effective to remove urea from dialysate in a pH range of between 4 and 12 and more particularly in a pH range of between about 6 and 8. In another embodiment the sorbent is soluble or substantially soluble and effective to bond with urea to remove, or bind urea from a dialysate solution or other aqueous solution.


In another aspect, a filter for regenerating dialysate includes a sorbent layer comprising a polymer having specific functional groups bonded thereto that interact or react with urea at a pH of between 4 and 12, and more particularly at a pH of between 6 and 8, to remove urea from an aqueous solution. The exemplary polymer may be any one of soluble, substantially soluble, insoluble and substantially insoluble in water. The exemplary polymer further reacts or interacts with urea while near room temperature or while in a defined temperature range between about 50° F. and 110° F. without releasing ammonia or generating carbon dioxide. The reaction product of the polymer and urea may also be any one of soluble, substantially soluble, insoluble and substantially insoluble in water. A second filter layer may be used with the exemplary polymer sorbent. The second filter layer comprises activated carbon for absorbing organic metabolites from the dialysate or other aqueous solution. In one variation, the filter further includes an anion exchange layer for removing anions from the dialysate.


In another aspect, a filter for removing urea from an aqueous solution or liquid is provided. The filter comprises a sorbent layer or coating. The sorbent layer or coating comprises a polymer having specific functional groups bonded thereto. The exemplary polymer having specific functional groups bonded thereto interacts or reacts with urea at a pH of between 4 and 12 or a predetermined bounded pH range therebetween (i.e., 3 to 7, 5-9, 6-8, etc.) Upon interaction or perhaps a reaction with urea, urea is bonded to the exemplary sorbent polymer and removed from an aqueous solution. An exemplary polymer may be soluble, substantially soluble, insoluble, or substantially insoluble in water. Furthermore, an exemplary polymer reacts with urea at near room temperature or other predetermined temperature range without releasing ammonia or generating carbon dioxide. In various aspects, an exemplary polymer reacts or interacts with urea to produce a single reaction product. The filter may also include activated carbon for adsorbing and removing other molecules from the aqueous solution. The reaction product produced by the reaction or interaction of an exemplary polymer and urea may be soluble, substantially soluble, insoluble, or substantially insoluble in water.





BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding, reference is now made to the following description taken in conjunction with the accompanying Drawings in which:



FIG. 1 illustrates a diagram of a dialyzer; and



FIG. 2 illustrates a cross-sectional diagram of a fiber lumen in a dialyzer.





DETAILED DESCRIPTION

Referring now to the drawings, the various views and embodiments of exemplary urea sorbents are illustrated and described, and other possible embodiments are described. The figures are not necessarily drawn to scale, and in some instances the drawings have been exaggerated and/or simplified in places for illustrative purposes only. One of ordinary skill in the art will appreciate the many possible applications and variations based on the following examples of possible embodiments.


Sorbent Preparation:


1. Preparation of MPS-IV-048 (Polyvinylglyoxalate)



embedded image


1.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol
1.000 g
5.0 × 10−3
1



(M. wt. = 205000)

(23.3 mmol of





alcohol units)


2
Glyoxylic acid
2.144 g
23.30
1



monohydrate



(M. wt. = 92)


3
EDC•HC1 (M. wt. =
3.973 g
20.72
0.88



191.71)


4
Distilled water
  15 ml









1.2 Procedure.


To a stirred solution of glyoxylic acid monohydrate and EDC.HCl in distilled water, polyvinyl alcohol was added stirred the solution for 24 h. Water was evaporated under reduced pressure to obtain a gum, which was used for urea trapping experiments from the dialysis solutions.


2. Preparation of MPS-IV-054 (Polyvinylglyoxalate)



embedded image


2.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol (M.
1.000 g
5.0 × 10−3
1



wt. = 205000)

(23.3 mmol of





alcohol units)


2
Glyoxylic acid
2.144 g
23.30
1



monohydrate



(M. wt. = 92)


3
NaH (M. wt. =
1.538 g
0.846
1.51



24 55-60%



in suspension)


4
Dry-N,N-
  10 ml



Dimethylformamide



(DMF)









2.2 Procedure


Sodium hydride was added to a cooled (0° C., ice bath) stirred suspension of polyvinyl alcohol in dry DMF and stirring continued for 2-3 min. Glyoxylic acid monohydrate was added to this mixture and the mixture was brought to room temperature after 2 h stirring at 0° C. Stirring continued for overnight. The solid obtained was washed with DCM and used for urea trapping experiments from the dialysis solutions.


2.3 Properties

    • Weight of MPS-IV-054=3.691 g
    • Melting Point of MPS-IV-054=doesn't melt up to 290 0° C.
    • Mn=75540; Mw=79736; ρ=1.055 g/cm3


3. Preparation of MPS-V-003 (Bis(Polyvinyloxalate))



embedded image


3.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol
1.000 g
5.0 × 10−3
1



(M. wt. = 205000)

(23.3 mmol of





alcohol units)


2
Oxalic acid (M. wt. =
2.000 g
25.64
1.1



78)


3
EDC•HC1 (M. wt. =
3.973 g
20.72
0.88



191.71)


4
Distilled water
  20 ml









3.2 Procedure


To a stirred solution of oxalic acid and EDC.HCl in distilled water, polyvinyl alcohol was added stirred the solution for 24 h. Water was evaporated under reduced pressure to obtain a gum, which was used for urea trapping experiments from the dialysis solutions.


3.3 Properties

    • Weight of MPS-V-003=6.20 g


4. Preparation of MPS-V-004 (Polyvinylpyruvate)



embedded image


4.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol
1.000 g
5.0 × 10−3
1



(M. wt. = 205000)

(23.3 mmol of





alcohol units)


2
Pyruvic acid
 2.10 ml
25.28
1.1



(M. wt. = 88.06; d =
(≡2.226 g)



1.06)


3
EDC•HC1 (M. wt. =
 3.92 g
20.44
0.88



191.71)


4
Distilled water
  15 ml









4.2 Procedure


To a stirred solution of pyruvic acid and EDC.HCl in distilled water, polyvinyl alcohol was added stirred the solution for 24 h. Water was evaporated under reduced pressure to obtain a gum, which was used for urea trapping experiments from the dialysis solutions.


4.3 Properties

    • Weight of MPS-V-004=6.42 g


5. Preparation of MPS-V-005 (Polyvinylbezoate 0.33 Polyvinylalcohol 0.66)



embedded image


5.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
2.000 g
1.0 × 10−2
1 × 10−2
1


Polyvinyl

(46.6 mmol
(46.6 mmole


alcohol

of alcohol
of alcohol


(M. wt. =

units)
units)


205000)


2
Benzoyl chloride
2.00 ml
17.23
0.37



(M. wt. =
(≡2.422 g)



130.57; d =



1.211)


3
Dry pyridine
  25 ml









5.2 Procedure


To a stirred, cooled (0° C., ice bath) solution of polyvinyl alcohol in dry pyridine (17 ml), a solution of benzoyl chloride in dry pyridine (8 ml) was added dropwise over a period of 10 min and stirring continued for 24 h with gradual increase in reaction temperature to rt. After 24 h, the pyridine was removed under reduced pressure and by co-evaporation with toluene to obtain a gum which was used for next step. The gum (MPS-V-005) swelled when brought in contact with solvents like ethyl acetate, dichloromethane (DCM), chloroform and methanol.


6. Preparation of MPS-IV-009 (Polyvinylbezoate 0.33 Polyvinylglyoxalate 0.66)



embedded image


6.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
MPS-V-005
2.000 g
(29.3 mmol of
1





alcohol units)


2
Glyoxylic acid
0.920 g
10.00
0.34



monohydrate (M.



wt. = 92)


3
EDC•HC1 (M.
 1.55 g
10.00
0.34



wt. = 191.71)


4
Distilled water
  20 ml









6.2 Procedure


A solution of glyoxylic acid monohydrate and EDC.HCl in distilled water was added to MPS-V-005 and the suspension was stirred at room temperature for 48 h. The white ppt obtained was filtered off, dried and used for urea trapping experiments from the dialysis solutions.


6.3 Properties

    • Weight of MPS-V-009=1.543 g


7. Preparation of MPS-V-027 (Polyvinylglyoxalate-Ethylene Copolymer)



embedded image


7.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol-
 2.28 g
41.67 mmol
1



coethylene (27%
(≡1.838 g of
of



ethylene)
polyvinyl alcohol)
OH group


2
Glyoxalic acid
 4.00 g
 43.48
1.04



monohydrate



(M. wt. = 92)


3
NaH (M. wt. =
1.200 g
 50.00
1.2



24 55-60%



in suspension)


4
Thionyl chloride
12 (≡19.572 g)
164.51
3.78



(M. wt. = 118.97,



d = 1.613)


5
Dry-N,N-
  30 ml



Dimethylformamide



(DMF)









7.2 Procedure


Glyoxylic acid monohydrate was dissolved in thionyl chloride and the mixture was refluxed for 48 h. Removal of excess thionyl chloride under vacuum gave a gum (glyoxaloyl chloride). Polyvinyl alcohol co-ethylene was dissolved in dry DMF (by warming up to 100° C.) and this solution was added (after cooling to about 40° C.) to the previously obtained gum. The mixture was stirred for about 30 min in ice bath and NaH was added. Stirring continued for overnight after removal of the ice bath to obtain a sticky solid which was used for the urea trapping experiments from the dialysis solutions.


7.3 Properties

    • Weight of MPS-V-027=4.763 g


8. Preparation of MPS-V-036

(polyacrylicacid0.9polyvinylpolyacrylicacid0.1)




embedded image


8.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent







1
Poly(acrylic acid)
1.500 g
3.75 × 10−4
1



(M. wt. = 4000000)

(20.83 mmol





of —COOH





units)


2
Polyvinyl alcohol
1.000 g
4.88 × 10−4
0.1



(M. wt. = 205000)

(2.27 mmol of





—OH units)


3
EDC•HC1
0.479 g
2.49
1.1 eq of —OH



(M. wt. = 191.71)


groups


4
Distilled water
  50 ml









8.2 Procedure


Poly (acrylic acid) was added to a stirred solution of EDC.HCl in distilled water. To this stirred suspension, polyvinyl alcohol was added and the solution was stirred for overnight. The gel obtained was filtered under suction (vacuum pump), washed with water, methanol, dichloromethane (DCM), acetone and ether respectively and dried for one week at room temperature to obtain a glassy solid, which was used for urea trapping experiments from the dialysis solutions.


8.3 Properties

    • Weight of MPS-V-036=3.361 g


9. Preparation of MPS-V-037 (Polyvinylpyrurate-Ethylene Copolymer)



embedded image


9.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol-
 1.14 g
20.84 mmol
1



coethylene (27%
(≡0.909 g of
of OH group



ethylene)
polyvinyl alcohol)


2
Pyruvic acid
 1.90 ml
27.19
1.3



(M. wt. =
(≡2.394 g)



88.06, d = 1.26)


3
DCC
6.450 g
31.26
1.5



(M. wt. 206.33)


4
DMAP (M. wt. =
0.382 g
 3.13
0.15



122.17)


5
Dry-N,N-
  30 ml



Dimethylformamide



(DMF)









9.2 Procedure


Polyvinyl alcohol co-ethylene was dissolved in DMF (15 ml) by heating the mixture to 100° C. This solution (after cooling to 40° C.) was added to a mixture of pyruvic acid, dicyclohexyl carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) in dry DMF (15 ml) and the reaction mixture was stirred at room temperature for overnight. The solid obtained was filtered off, washed with water, methanol, dichloromethane (DCM), acetone and ether respectively, dried and used for the urea trapping experiments from the dialysis solutions.


9.3 Properties

    • Weight of MPS-V-037=6.305 g


10. Preparation of MPS-V-038 (Polyvinylglyoxalate-Ethylene Copolymer)



embedded image


10.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent



















1
Polyvinyl alcohol-
 1.14 g
20.84 mmol
1



coethylene (27%
(≡0.909 g of
of OH group



ethylene)
polyvinyl alcohol)


2
Glyoxylic acid
2.400 g
26.09
1.25



monohydrate (M.



wt. = 92)


3
DCC (M. wt. =
6.450 g
31.26
1.5



206.33)


4
DMAP (M. wt. =
0.382 g
 3.13
0.15



122.17)


5
Dry-N,N-
  30 ml



Dimethylformamide



(DMF)









10.2 Procedure


Polyvinyl alcohol co-ethylene was dissolved in DMF (15 ml) by heating the mixture to 100° C. This solution (after cooling to 40° C.) was added to a mixture of glyoxylic acid monohydrate, dicyclohexyl carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) in dry DMF (15 ml) and the reaction mixture was stirred at room temperature for overnight. The solid obtained was filtered off, washed with water, methanol, dichloromethane (DCM), acetone and ether respectively, dried and used for the urea trapping experiments from the dialysis solutions.


10.3 Properties

    • Weight of MPS-V-038=6.025 g


11. Preparation of MPS-V-047 (Isopropylaminepolyacrylicamide)



embedded image


11.1 Reagents
















Entry
Reagent/solvent
Amount
mmol
Equivalent







1
Poly(acrylic acid)
1.500 g
3.75 × 10−4
1



(M. wt. = 4000000)

(20.83 mmol





of —COOH





units)


2
iso-Propylamine (M.
 0.20 ml
2.33
0.11



wt. = 59.11, d =
(≡0.138 g)



0.688)


3
EDC•HC1 (M. wt. =
0.479 g
2.49
1.1 eq of



191.71)


—OH






groups


4
Distilled water
  50 ml









11.2 Procedure


Poly(acrylic acid) was added to a stirred solution of EDC.HCl in distilled water. To this stirred suspension, iso-propylamine was added and the solution was stirred for overnight. The gel obtained was filtered under suction (vacuum pump), washed with water, methanol, dichloromethane (DCM), acetone and ether respectively and dried for one week at room temperature to obtain a thick gel (like a glassy solid), which was used for urea trapping experiments from the dialysis solutions.


11.3 Properties

    • Weight of MPS-V-047=2.46 g


Dialysate solutions were analyzed for nitrogen content and the amount of urea in the dialysate was calculated. In some cases, additional urea was added to the solution as indicated in column 2 of each Table (1-5). The polymer reagent was added to the solution in the amount indicated in column 3. The mixture was stirred at room temperature for one hour and filtered. The filtrate was analyzed and the amount of urea removed from the dialysate solution was determined. A minus sign (−) indicates that the results were inconclusive.


In the following tables, the title identifies the particular polymer reagent tested. The first column of each table represents the experiment or run number. The second column identifies the particular dialysate solution used for the experiment and whether additional urea was added to the solution. The third column indicates the amount of polymer reagent used in the experiment. The fourth column gives the reaction conditions e.g. time and temperature. (Note: rt=room temperature). It is further understood that room temperature is between about 60 and 78° F. (about 15.56° C. to about 25.56° C.) and that reactions will also occur in a temperature range of between about 50° F. to about 110° F. (about 10° C. to about 43.3° C.). It is believed that reactions will also occur at colder or warmer temperatures, but such reactions have not been specifically tested. The fifth column identifies the analyzed portion of the reaction mixture (e.g. filtrate). In some cases, a neutralizing agent was added to the filtrate. The sixth column (BUN or Blood Urea Nitrogen) provides the concentration of nitrogen in the particular dialysate solution used for the experiment. The seventh column gives the amount of urea in the solution. The eighth column contains the maximum amount of urea in the solution. In the cases where additional urea was added as indicated in column 2, this number will be higher than the corresponding entry in the sixth column. The ninth column is the amount of urea removed from the dialysate solution. The first row of each table provides the nitrogen, urea and maximum or total amount of urea present in the dialysate solution used in the experiments.









TABLE 1







MPS-IV-048









Results (in mg/dL)

















Amount of

Analyzed
Blood
Blood
Maximum
Amount




Reagent

portion of
Urea
Urea
amount of
of urea



Soln
Used
Reaction
reaction
Nitrogen
(BUN ×
urea
taken out


Entry
compn
(g)
condn.
mixture
(BUN)
2.14)
present
(mg/dL/h)


















1
Soln-3



7.8
16.692
16.692




Blank



(10 ml)


2
Soln-3
 2
rt, 1 h
Filtrate
14.6
31.244
16.692
(−) 14.552



(10 ml)


(8 mL)


3
Soln-3
13
rt, 1 h
Filtrate
797.2
1706.0
2516.7
810.7



(20 ml) +
(0.50 g)

(10 mL)



Urea



(0.50 g)
















TABLE 2







MPS-IV-OS4 and MPS-V-009









Results (in mg/dL)



















Analyzed



Amount




Amount of

portion
Blood
Blood
Maximum
of urea




Reagent

of
Urea
Urea
amount of
taken



Soln
Used
Reaction
reaction
Nitrogen
(BUN ×
urea
out


Entry
compn
(g)
condn.
mixture
(BUN)
2.14)
present
(mg/dL/h)


















1
Soln-3



4
8.56
8.56




Blank



(10 ml)







MPS-IV-054















2
Soln-3
2.5 
rt, 1 h
Filtrate
2227
4765.78
5008.56
242.78



(20 ml) +


(5 ml;



Urea


pH = 10)



(0.50 g)


3
Soln-3
2.50
rt, 1 h
Filtrate
2523
5399.22
5008.56
(−)



(10 ml) +


(3 ml;



390.66



Urea


pH = 10) +



(1.00 g)


2% HCI-






(0.4 ml)






to






neutralize






to pH = 7







MPS-V-009















4
Soln-3
1.26
rt, 1 h
Filtrate
2563
5484.82
2508.56
(−)



(10 ml) +


(3 ml;



2976.26 



Urea


pH = 7)



(0.50 g)
















TABLE 3







MPS-V-003









Results (in mg/dL)

















Amount of

Analyzed
Blood
Blood
Maximum
Amount




Reagent

portion of
Urea
Urea
amount of
of urea



Soln
Used
Reaction
reaction
Nitrogen
(BUN ×
urea
taken out


Entry
compn
(g)
condn.
mixture
(BUN)
2.14)
present
(mg/dL/h)


















1
Soln-3



4
8.56
8.56




(10 ml)



Blank


2
Soln-3

rt, 1 h
Filtrate
2257
4740
5008
268.3



(20 ml) +


(5 mL;



Urea


pH = 1)



(1.00 g)


3
Soln-3

rt, 1 h
Filtrate
1527
3267.78
5008
1740.22



(20 ml) +


(3 m;



Urea


pH = 1) +



(1.00 g)


saturated






HCO3






(1 ml) to






neutralize






to pH = 7
















TABLE 4







MPS-V-027 and MPS-V-036









Results (in mg/dL)























Amount




Amount

Analyzed
Blood
Blood
Maximum
of urea




of

portion of
Urea
Urea
amount of
taken



Soln
Reagent
Reaction
reaction
Nitrogen
(BUN ×
urea
out


Entry
compn
Used (g)
condn.
mixture
(BUN)
2.14)
present
(mg/dL/h)


















1
Soln-4



88
188.32
188.32




Blank



(9 ml)


2
Soln-4
MPS-V
rt, 1 h
Filtrate
0
0
2688.32
2688.32



(10 ml) +
036

(2 ml)



Urea
(residue

(pH = 6~7)



(0.50 g)
after




filtration)




(2.28 g)


3
Soln-4
MPS-V
rt, 1 h
Filtrate
1114
2339.4
2688.32
349.3



(10 ml) +
027

(4 ml)



Urea
(residue

(pH = 7~8)



(0.50 g)
after




filtration




and




washing




with




MeOH)




(4.40 g)
















TABLE 5







MPS-V-037, MPS-V-038 and MPS-V-047


Data for Solution-4









Results (in mg/dL)























Amount




Amount

Analyzed
Blood
Blood
Maximum
of urea




of

portion of
Urea
Urea
amount of
taken



Soln
Reagent
Reaction
reaction
Nitrogen
(BUN ×
urea
out


Entry
compn
Used (g)
condn.
mixture
(BUN)
2.14)
present
(mg/dL/h)


















1
Soln-4



25
53..5
53..5




Blank



(9 ml)


2
Soln-4
 2
rt, 1 h
Filtrate
0
0
5053.5
5053.5



(20 ml) +


(10 ml)



Urea


(pH-7)



(1.00 g)


3
Soln-4
13
rt, 1 h
Filtrate
0
0
2553.5
2553.5



(10 ml) +
(0.50 g)

(10 ml)



Urea


(pH-7)



(0.50 g)


4
Soln-4
MPS-V
rt, 1 h
Filtrate
479
1025.06
2553.5
1528.44



(10 ml) +
047

(5 ml)



Urea
(2.46 g)

(pH = 5)



(0.50 g)









As will be appreciated from the foregoing, vinyl polymers having specific functional groups selected from carboxylic acids, esters and salts, amides, dicarboxylic acids, and esters and salts may be formulated to provide sorbents suitable for use in removing urea from an aqueous solution having a pH from about 6 to 8. Other sorbents suitable for removing urea from an aqueous solution having a pH range from 4 to 12 are realizable with various ones of the aforementioned specific functional groups by one of ordinary skill in the art having the information contained herein. Such exemplary polymers are substantially insoluble in water and can remove urea from dialysate at a rate of at least 2.5 mg/dl/hr. Additionally, such polymers may be soluble, substantially soluble or insoluble in water depending on variations in their manufacture.


In some variations of the invention, vinyl polymers such as polyvinyl alcohol, polyvinyl alcohol-ethylene co-polymers and polyacrylic acid are reacted with specific functional groups selected from carboxylic acids, carboxylic acid esters, carboxylates, amides, dicarboxylic acids, dicarboxylic acid esters, and dicarboxylates to produce the desired exemplary sorbents. Exemplary polymers may be applied to various substrates for use as dialysis sorbents. Such substrates may be organic or inorganic and may include filter paper, plastic or glass beads and other particulate materials that are insoluble in water. The polymers may also be applied to various screens and mesh-type filter materials formed from wire or plastic strands or cloth.


Another advantage of an exemplary urea sorbent is the use of selective functional groups that can be utilized to make a variety of resultant exemplary sorbents ranging from being soluble, insoluble, a liquid, a gum, an adhesive, a flexible material, a coating as well as a solid or powder.


It will be appreciated by those skilled in the art having the benefit of this disclosure that this urea sorbent provides a viable replacement for prior known dialysis sorbent materials. It should be understood that the drawings and detailed description herein are to be regarded in an illustrative rather than a restrictive manner, and are not intended to be limiting to the particular forms and examples disclosed. On the contrary, included are any further modifications, changes, rearrangements, substitutions, alternatives, design choices, and embodiments apparent to those of ordinary skill in the art, without departing from the spirit and scope hereof, as defined by the following claims. Thus, it is intended that the following claims be interpreted to embrace all such further modifications, changes, rearrangements, substitutions, alternatives, design choices, and embodiments.


While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims
  • 1. A filter for regenerating dialysate comprising: a sorbent layer comprising a polymer having specific functional groups bonded thereto that interact with urea at a pH of between 5 and 10 to remove urea from an aqueous solution, wherein the polymer is substantially insoluble in water and interacts with urea in a predetermined temperature range and without releasing ammonia and wherein the reaction product of the polymer and urea is substantially insoluble in water; andactivated carbon for absorbing organic metabolites from the dialysate.
  • 2. The filter of claim 1, further comprising an anion exchange layer for removing anions from the dialysate.
  • 3. A dialysate regenerating filter for removing solids or liquids from dialysate comprising: a sorbent layer comprising a polymer having functional groups bonded thereto that interact or react with urea at a pH of between 4 to 12 and bind urea from an aqueous solution, wherein the polymer is either soluble or substantially insoluble in water and interacts or reacts with urea without releasing ammonia and wherein the interaction or reaction product of the polymer and urea is either soluble or substantially insoluble in water; andactivated carbon for absorbing organic metabolites from the dialysate.
  • 4. The filter of claim 3, further comprising an anion exchange layer for removing anions from the dialysate.
  • 5. The filter of claim 3, wherein the functional groups interact or react with urea at a pH of between 6 and 9.
  • 6. The filter of claim 3, wherein the polymer is insoluble in water.
  • 7. The filter of claim 3, wherein the interaction or reaction product of the polymer and urea is insoluble in water.
RELATED APPLICATION(S)

This application is a divisional of U.S. application Ser. No. 13/541,107, filed Jul. 3, 2012, now abandoned which is a divisional of U.S. application Ser. No. 12/479,513, filed Jun. 5, 2009, now U.S. Pat. No. 8,220,643, which claims the benefit of U.S. Provisional Application No. 61/059,610, filed on Jun. 6, 2008. The entire teachings of the above application(s) are incorporated herein by reference.

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Number Name Date Kind
8220643 Eisen Jul 2012 B2
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20080292579 Brooks et al. Nov 2008 A1
Foreign Referenced Citations (1)
Number Date Country
WO 0240039 May 2002 WO
Non-Patent Literature Citations (2)
Entry
International Search Report, International Application No. PCT/US2010/037637, date of mailing: Feb. 25, 2011.
Notification Concerning Transmittal of International Preliminary Report on Patentability for PCT/US2010/037637, date of mailing: Dec. 15, 2011.
Related Publications (1)
Number Date Country
20130313188 A1 Nov 2013 US
Provisional Applications (1)
Number Date Country
61059610 Jun 2008 US
Divisions (2)
Number Date Country
Parent 13541107 Jul 2012 US
Child 13953565 US
Parent 12479513 Jun 2009 US
Child 13541107 US