US4668400A — Hemodialysis processes and hemodialysis solutions

Claim 1

Independent Claim 558 words

A process for determining the permeant ion composition in a complex physiological electrolyte solution existing on each side of a dialysis membrane, such solution on one side of such membrane corresponding to a dialyzing fluid, and such solution on the other side of such membrane corresponding to blood plasma from a patient whose blood is being hemodialyzed through such membrane, said process accomplishing both: (1) adjusting the charge on at least one non permeant polyionic material existing on one side of the membrane by regulating the pH on at least one side of the membrane, and (2) determining the ionic composition of permeant ions on one side of the membrane by selecting the permeant ion concentrations on the other side of the membrane, said process comprising the steps of: (A) estimating the approximate molar concentration of albumin in said blood plasma, (B) selecting a particular pH value for said blood plasma, thereby to make the electrolyte solution existing on one side of said membrane have such pH and consequently thereby to set the approximate anionic valence of said albumin in said blood plasma, and where, in equation (3), Z is defined as the valence of the non permeant polyionic material, mainly serum albumin, whose valence varies with pH in accordance with the following approximately linear relationship: ______________________________________ Z.sup.- Charge on 1 mole pH serum albumin ______________________________________ 5.1 0 5.6 -7.5 6.6 -13.5 7.4 -20.5 8.0 -27 8.8 -33.2 ______________________________________ and further where said selected pH value determines the value of Z as represented in said relationship, (C) specifying the desired ion concentrations in millimoles per liter of fluid water of permeant ions present in the electrolyte solution existing on one side of said membrane in accord with the following equation (1) ##EQU3## wherein: subscript i designates a permeant ion in said plasma, subscript o designates a permeant ion in said dialyzing fluid, and each chemical symbol in square bracket designates concentration in millimole per liter of fluid water provided that, when any given ion specified in said equation (1) is not present, then that ratio which incorporates such ion is dropped and said equation (1) is thereby amended, thus, to identify all permeant ions to be considered in both electrolyte solutions, and further, provided that, if the chosen so specified ion concentrations are in dialysis fluid, the sum charge of all cations equals the sum charge of anions in conformity with following equation (2): ##STR1## or, if the chosen so specified ion concentrations are in plasma, the sum charge of all cations equals sum charge of all anions in conformity with following equation (3): ##EQU4## which such equations (2) and (3) state that electrical neutrality exists in both solutions, (D) multiplying each specified ion concentration by a ratio of one chosen pair of ions appearing in said amended equation (1), (E) substituting these resulting so multiplied specified ion concentrations into either said equation (2) or said equation (3), depending upon whether the ion composition being determined is for a dialyzing fluid or for a hemodialyzed said blood plasma, and regrouping the terms of the resulting equation, (F) effecting an algebraic solution for the unknown ion ratio so selected, and (G) using the said algebraic solution of said ion ratio by substituting said algebraically solved ratio into equation (1), thus identifying the concentration of each of the unknown ions.

Claim 2

Dependent Claim 558 words

A process for determining the permeant ion composition in a complex physiological electrolyte solution existing on each side of a dialysis membrane, such solution on one side of such membrane corresponding to a dialyzing fluid, and such solution on the other side of such membrane corresponding to blood plasma from a patient whose blood is being hemodialyzed through such membrane, said process accomplishing both: (1) adjusting the charge on at least one non permeant polyionic material existing on one side of the membrane by regulating the pH on at least one side of the membrane, and (2) determining the ionic composition of permeant ions on one side of the membrane by selecting the permeant ion concentrations on the other side of the membrane, said process comprising the steps of: (A) estimating the approximate molar concentration of albumin in said blood plasma, (B) selecting a particular pH value for said blood plasma, thereby to make the electrolyte solution existing on one side of said membrane have such pH and consequently thereby to set the approximate anionic valence of said albumin in said blood plasma, and where, in equation (3), Z is defined as the valence of the non permeant polyionic material, mainly serum albumin, whose valence varies with pH in accordance with the following approximately linear relationship: ______________________________________ Z.sup.- Charge on 1 mole pH serum albumin ______________________________________ 5.1 0 5.6 -7.5 6.6 -13.5 7.4 -20.5 8.0 -27 8.8 -33.2 ______________________________________ and further where said selected pH value determines the value of Z as represented in said relationship, (C) specifying the desired ion concentrations in millimoles per liter of fluid water of permeant ions present in the electrolyte solution existing on one side of said membrane in accord with the following equation (1) ##EQU3## wherein: subscript i designates a permeant ion in said plasma, subscript o designates a permeant ion in said dialyzing fluid, and each chemical symbol in square bracket designates concentration in millimole per liter of fluid water provided that, when any given ion specified in said equation (1) is not present, then that ratio which incorporates such ion is dropped and said equation (1) is thereby amended, thus, to identify all permeant ions to be considered in both electrolyte solutions, and further, provided that, if the chosen so specified ion concentrations are in dialysis fluid, the sum charge of all cations equals the sum charge of anions in conformity with following equation (2): ##STR1## or, if the chosen so specified ion concentrations are in plasma, the sum charge of all cations equals sum charge of all anions in conformity with following equation (3): ##EQU4## which such equations (2) and (3) state that electrical neutrality exists in both solutions, (D) multiplying each specified ion concentration by a ratio of one chosen pair of ions appearing in said amended equation (1), (E) substituting these resulting so multiplied specified ion concentrations into either said equation (2) or said equation (3), depending upon whether the ion composition being determined is for a dialyzing fluid or for a hemodialyzed said blood plasma, and regrouping the terms of the resulting equation, (F) effecting an algebraic solution for the unknown ion ratio so selected, and (G) using the said algebraic solution of said ion ratio by substituting said algebraically solved ratio into equation (1), thus identifying the concentration of each of the unknown ions.

Claim 3

Dependent Claim 22 words

The process of claim 1 wherein said assigning in said step (A) is carried out by determining total blood |Z|[protein z- ].

Claim 4

Dependent Claim 16 words

The process of claim 1 wherein the ion composition of a dialyzing fluid is so determined.

Claim 5

Dependent Claim 17 words

The process of claim 3 wherein said dialyzing fluid is prepared according to such so determined composition.

Claim 6

Dependent Claim 195 words

The process of claim 4 wherein the anion gap in said hemodialysis solution is supplied by at least one of the following near equilibrium couples in the respective quantities indicated: (1) from 0 to about 80 millimoles per liter of a first couple mixture consisting of bicarbonate anions and carbon dioxide wherein the milliequivalent ratio of said bicarbonate anions to said carbon dioxide ranges from about 0.1:1 to 55/0.1, (2) from 0 to about 80 millimoles per liter of a second couple mixture consisting of 1-lactate anions and pyruvate anions wherein the milliequivalent ratio of said 1-lactate anions to said pyruvate anions ranges from about 20:1 to 1:1, and (3) from about 0 to about 80 millimoles per liter of a third couple mixture consisting of d-betahydroxybutyrate anions and acetoacetate anions wherein the milliequivalent ratio of said d-betahydroxybutyrate to said acetoacetate ranges from about 6:1 to 0.5:1, and wherein each of the respective quantities chosen is entered into the forgoing said equations before said step (E) is practiced, and further wherein values for the quantities of such near equilibrium couples so chosen and so calculated are utilized in preparing said solution in said step (F).

Claim 7

Dependent Claim 67 words

The process of claim 4 wherein said solution is characterized further, and is so prepared in step (F) to have an interrelationship between water and all solutes comprising such solution such that: (1) the milliosmolarity ranges from about 260 to 765, (2) the pH ranges from about 5 to 9, and (3) the milliequivalent ratio of sodium cations to chloride anions ranges from about 1.24 to 1.55.

Claim 8

Dependent Claim 13 words

A hemodialysis solution which has been prepared by the process of claim 4.

Claim 9

Dependent Claim 183 words

The process of claim 3 wherein the pH of said dialyzing fluid is set by following the steps of (A) dissolving CO 2 gas in an aqueous medium in a total quantity sufficient to achieve a predetermined concentration in accordance with the relationship: ##EQU5## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as concentration of carbon dioxide in said solution in millimoles per liter solution water, and (B) adding sufficient bicarbonate into said solution so as to achieve a concentration thereof which is sufficient together with said dissolved CO 2 concentration to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU6## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, and [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 10

Dependent Claim 180 words

The process of claim 8 wherein the pH of said dialyzing fluid is set by following the steps of (A) adding sufficient bicarbonate in an aqueous solution in a total quantity sufficient to achieve a predetermined concentration, and (B) dissolving sufficient CO 2 gas in such resulting solution to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU7## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as the concentration of carbon dioxide in said solution expressed as millimoles per liter solution water, thereby to produce a solution having a pH as defined in accordance with the relationship: ##EQU8## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, and [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 11

Dependent Claim 23 words

The process of claim 1 wherein the ion composition of said patient's blood returning to said patient from hemodialysis apparatus is so determined.

Claim 12

Dependent Claim 185 words

A process for establishing the pH of a bicarbonate containing physiological electrolyte solution with gaseous CO 2 comprising the steps of: (A) dissolving CO 2 gas in an aqueous medium in a total quantity sufficient to achieve a predetermined concentration in accordance with the relationship: ##EQU9## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as concentration of carbon dioxide in said solution expressed as millimoles per liter solution water, and (B) adding sufficient bicarbonate in said solution so as to achieve a concentration thereof which is sufficient together with said dissolved CO 2 concentration to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU10## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 13

Dependent Claim 185 words

A process for establishing the pH of a bicarbonate containing physiological electrolyte solution with gaseous CO 2 comprising the steps of: (A) dissolving CO 2 gas in an aqueous medium in a total quantity sufficient to achieve a predetermined concentration in accordance with the relationship: ##EQU9## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as concentration of carbon dioxide in said solution expressed as millimoles per liter solution water, and (B) adding sufficient bicarbonate in said solution so as to achieve a concentration thereof which is sufficient together with said dissolved CO 2 concentration to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU10## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 14

Dependent Claim 181 words

A process for establishing the pH of a bicarbonate containing electrolyte solution with gaseous CO 2 comprising the steps of: (A) adding sufficient bicarbonate into an aqueous solution in a total quantity sufficient to achieve a predetermined concentration, and (B) dissolving sufficient CO 2 gas in such resulting solution to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU11## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as the concentration of carbon dioxide in said solution expressed as millimole per liter solution water, thereby to produce a solution having a pH as defined in accordance with the relationship: ##EQU12## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, and [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 15

Dependent Claim 181 words

A process for establishing the pH of a bicarbonate containing electrolyte solution with gaseous CO 2 comprising the steps of: (A) adding sufficient bicarbonate into an aqueous solution in a total quantity sufficient to achieve a predetermined concentration, and (B) dissolving sufficient CO 2 gas in such resulting solution to produce a specified pH in the range from about 5 to 9 in accordance with the relationship ##EQU11## wherein: pCO 2 is defined as the partial pressure of the CO 2 gas being dissolved in mm of Hg, α is defined as the milliliters CO 2 dissolved in one milliliter of solution, and [CO 2 ] is defined as the concentration of carbon dioxide in said solution expressed as millimole per liter solution water, thereby to produce a solution having a pH as defined in accordance with the relationship: ##EQU12## wherein: pKa' is defined as the apparent dissociation constant of carbonic acid under physiological conditions, [CO 2 ] is as defined above, and [HCO 3 ] is defined as the concentration in millimoles per liter of bicarbonate present in said solution.

Claim 16

Dependent Claim 107 words

In a hemodialysis delivery apparatus of the type which delivers hemodialysis fluid to a hemodialyzer and which incorporates in addition to a hemodialyzer (a) dialysis fluid supply pump means, (b) dialysis fluid supply pressure regulating means, (c) dialysis fluid supply temperature regulating means, (d) dialysis fluid supply flow regulating means, (e) dialysis fluid supply means, and (f) conduit means interconnecting said pump means, said regulating means, and said supply means, the improvement which comprises incorporating into said supply means: (A) means for dissolving CO 2 gas in said hemodialysis fluid, (B) means for regulating the dissolved CO 2 concentration in said hemodialysis fluid at a predetermined pH.

Claim 17

Dependent Claim 107 words

In a hemodialysis delivery apparatus of the type which delivers hemodialysis fluid to a hemodialyzer and which incorporates in addition to a hemodialyzer (a) dialysis fluid supply pump means, (b) dialysis fluid supply pressure regulating means, (c) dialysis fluid supply temperature regulating means, (d) dialysis fluid supply flow regulating means, (e) dialysis fluid supply means, and (f) conduit means interconnecting said pump means, said regulating means, and said supply means, the improvement which comprises incorporating into said supply means: (A) means for dissolving CO 2 gas in said hemodialysis fluid, (B) means for regulating the dissolved CO 2 concentration in said hemodialysis fluid at a predetermined pH.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1990-05-25	1990-11-24	1991-05-26	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1994-05-25	1994-11-24	1995-05-26	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1998-05-25	1998-11-24	1999-05-26	$7700.00	Window Closed / Lapsed

Hemodialysis processes and hemodialysis solutions

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