WO1998010745A1

WO1998010745A1 - Batch quantity dialysate chemical formulations

Info

Publication number: WO1998010745A1
Application number: PCT/US1997/014094
Authority: WO
Inventors: Dilip H. Shah; Rodney S. Kenley
Original assignee: Aksys, Ltd.
Priority date: 1996-09-11
Filing date: 1997-08-12
Publication date: 1998-03-19
Also published as: AU3976697A

Abstract

The present invention constitutes batch quantity dialysate formulations that are suitable for use in preparing a batch quantity of dialysate solution. The dialysate chemical formulations for one batch of dialysate comprise a liquid acid concentrate unit stored in a first vessel, and a dry bicarbonate unit stored in a second vessel. The contents of the first and second vessels are emptied into a dialysate preparation tank and mixed with water to form a batch quantity of dialysate solution. In a preferred embodiment, the liquid acid concentrate comprises (a) about 79.244-158.489 g/L of sodium chloride; (b) between about 0 and about 40.441 g/L of potassium chloride; (c) about 34.888 g/L of calcium chloride dihydrate; (d) between about 6.893 and about 20.680 g/L magnesium chloride hexahydrate; (e) about 339.00 g of dextrose; (f) about 36.643 g/L of acetic acid; and (g) water in sufficient amount to bring up to about 290-440 mL final volume. In a preferred embodiment, the dry bicarbonate unit contains between about 271.6 and about 358.4 g of sodium chloride; and between about 143.5-204.7 g of sodium bicarbonate.

Description

BATCH QUANTITY DIALYSATE CHEMICAL FORMULATIONS

BACKGROUND OF THE INVENTION

A. Cross Reference

This application is a continuation-in-part of U.S. patent application Ser. No. 08/388,275, filed February 13, 1995.

B. Field of the invention

This invention relates generally to chemical formulations that are used for the preparation of dialysate solutions, and more particularly to the distribution of chemicals into two dialysate concentrate formulations that are particularly suitable for use in preparing batch quantities of dialysate. In the present context, the term "batch" refers to the quantity of dialysate constituents, that when mixed with the proper amount of water, forms enough dialysate solution sufficient for one complete dialysis session for a single patient.

C. Statement of Related Art

Dialysis, including hemodialysis and peritoneal dialysis, is a treatment for patients that suffer from inadequate kidney function. In hemodialysis, blood is pumped from the patient's body through an extracorporeal artificial kidney circuit, where blood-borne toxins and excess water are filtered out of the blood through a semipermeable dialyzer membrane into an electrolyte (dialysate) medium. In peritoneal dialysis, the patient infuses a quantity of dialysate into the peritoneal cavity, and the peritoneal membrane acts as the semipermeable membrane. After a dwell period, the dialysate fluid is drained and a fresh supply of peritoneal dialysate is added to the peritoneum. A variety of concentrate formulations for preparing dialysis solutions used in hemodialysers or in peritoneal dialysis are known. See, for instance, U.S. Patent Nos. 4,336,881 ; 4,489,535; and 4,756,838. These formulations vary not only with respect to specific constituents, but also with respect to the concentrations of these constituents. Generally, concentrate formulations include sodium chloride as the major constituent and potassium chloride, calcium chloride and magnesium chloride as minor constituents. If required by the patient, dextrose may also be included. Sodium acetate and/or sodium bicarbonate are also included as a buffer source to correct for metabolic acidosis With acetate buffer, all of the constituents can be combined into a single concentrate. With bicarbonate buffer, two concentrates are necessary to prevent the precipitation of calcium and magnesium as carbonate salts.

One concentrate, usually called the acid concentrate, contains the chloride salts of sodium, potassium, calcium and magnesium, along with an acid such as acetic acid. The other concentrate, called the bicarbonate concentrate, contains sodium bicarbonate and usually sodium chloride as well. Both concentrates may exist in either liquid or powdered form. The sequential mixing of the two concentrates with purified water generates carbonic acid as a reaction product of the acid with bicarbonate and results in a dialysate having a pH within physiological limits but with sufficient acidity to prevent calcium and magnesium carbonate precipitation. A number of dialysate delivery systems are available for preparing and delivering dialysate. Traditionally, dialysis systems were used for the preparation of large batches ( e.g. , 120 L) of dialysate. Single batches were prepared by adding dialysate constituents to a batch tank with a predetermined amount of purified water and mixing until dissolution occurred to yield a dialysate having a final desired concentration. A reference describing the preparation of a large quantity of dialysate off-line in 50 liter carboys in a factory-like facility is S.T. Boen et al., Periodic Peritoneal Dialysis Using T)ιe Repeated Puncture Technique And An Automatic Cycling Machine, Vol. X Trans. Amer. Soc. Artif. Int. Organs, 44. 409-414 (1964). With the advent of on-line proportioning systems, dialysates can be prepared continuously on-line by combining water, which has been first purified by a separate water treatment system, with liquid concentrates of the dialysate constituents using a proportioning pump. A representative patent discussing this technique is the patent to Serfass, U.S. No. 3,441 , 135. Proportioning systems are considered to be less advantageous for use in a home hemo- or peritoneal dialysis machine, as compared to a batch system, because: (a) proportioning systems are dependent on two or three pumps to meter concentrate and water accurately and thus, instantaneous variation in flow rates can cause undesirable concentration changes. In contrast, a batch system has only one pump and quality of dialysate is assured throughout the treatment cycle; (b) loss of one or more pumps in proportioning system can cause serious harm to the patient if unattended for long periods of time whereas batch system pump failure simply stops dialysis and the patient is not subjected to harmful dialysate anytime; (c) proportioning systems have more moving parts and hence are subjected to more wear and tear and subsequent break down; and (d) adjustment of dialysate flow rates in proportioning systems requires adjustments of concentrate pump flow rates whereas in batch systems, a simple adjustment in one pump flow is all that is required. Moreover, batch systems are safer to use because a one time check of conductivity assures good quality dialysate until the quantity of the batch is used up.

It is therefore an object of the invention to provide for concentrate formulations of dialysate constituents that are suitable for preparation of batch quantities of dialysate. It is a further object of the invention to provide for batch dialysate concentrate formulations that are particularly suited for automatic mixing of the constituents in a dialysate tank. A fuπher object of the invention is to provide concentrate formulations that assures patient safety and will withstand temperature extremes when the concentrates are shipped from the location where they are formulated and bottled to the eventual destination.

SUMMARY OF THE INVENTION

The present invention constitutes batch quantity dialysate formulations that are suitable for use in preparing a batch quantity of dialysate solution, and kits and methods employing the same. The dialysate chemical formulations for one batch of dialysate comprise a liquid acid concentrate unit stored in a first vessel, and a dry bicarbonate concentrate unit stored in a second vessel. The contents of the first and second vessels are emptied into a dialysate preparation tank and mixed with water to form a batch quantity of dialysate solution. The mixing of chemicals and dilution with water is accomplished in an enclosed environment, under small pressure such that carbon dioxide formed remains dissolved in the solution. The present invention relates specifically to the dialysate chemical formulations; the vessels containing the chemicals and the machine that prepares the solution are not considered a part of the present invention per se.

Presently preferred formulations for the liquid acid concentrate and dry bicarbonate units are set forth in Tables 4 and 5, respectfully.

DETAILED DESCRIPTION OF THE PREFERRED XMBODIMENT

The assignee of the present invention has developed a daily hemodialysis machine that is particularly suitable for use in the home, nursing home, and limited care environment. The machine is described in patent application of Kenley et al. , Serial No. 08/388,275, filed February 13, 1995, and is incorporated by reference herein. The machine prepares the dialysate solution a batch at a time, just prior to the start of the dialysis session The dialysate chemicals are shipped to the machine site in vessels that each contain the batch quantity of either powdered or liquid dialysate chemicals. In a preferred embodiment of the invention, the dialysate chemicals are used in conjunction with the machine descπbed in the above Kenley et al. application.

To prepare the dialysate solution, dry dialysate chemicals in one batch quantity vessel, and liquid dialysate chemicals from one batch quantity vessel are dispersed into the dialysate tank. This process is descπbed in detail in the above-referenced Kenley et al. patent application. The present invention contemplates dialysate concentrate formulations for preparing bicarbonate-based dialysate in batch quantities, consisting of a dry bicarbonate concentrate and a liquid acid concentrate which are stored in separate containers and vessels and mixed together in a suitable dialysate solution tank to form a batch quantity of a physiologically balanced dialysate solution suitable for hemodialysis. The acid concentrates and bicarbonate concentrates of the invention are specially formulated to allow a physician to selectively tailor a dialysate formulation to a patient's particular health needs and to allow a patient to easily prepare batch size quantities of dialysate using a home dialysis machine described in Kenley et al. patent application. The final dialysate preferably includes the following constituents (Table 1 ):

TABLE 1: FINAL DIALYSATE RANGE

Constituent Concentration Ionic Strength

(g/L) (mEq/L)

NaCl 5.289 - 6.984 130-150 (Na⁺)

KC1 0.000-0.298 0 - 4 (K⁺)

CaCl₂.2H₂O 0.000-0.258 0.00 - 3.50 (Ca⁺)

MgCl₂.6H₂O 0.051-0.152 0.5 - 1.5 (Mg^{+ +})

NaHCO₃ 2.562-2.944 30.5 - 39 (HCO₃ ⁺)

CHjCOONa 0.000-0.612 0 - 4.5 (CHjCOO )

Dextrose Anhydrous 0-2.5 NA

Chloride as NaCl 5.318-7.510 91.0 - 128.5 (C1-)

Conductivity Range 12.8-15 mS/cm 140 - 160 (total average)

The acid concentrate of the invention includes sodium chloride, dextrose and minor amounts of chloride salts of potassium, calcium and magnesium in acetic acid. Dextrose is included in the acid concentrate in solubilized form to circumvent any potential dissolution problems in preparing the final dialysate formulation. In the preferred embodiment of the invention, the acid concentrate (410 mL volume per unit) is prepackaged in container, admixed with the bicarbonate concentrate in a dialysate preparation tank with a predetermined volume of water, then diluted to produce a 56 L batch dialysate using a home dialysis system suςh as the one described in the above referenced Kenley et al. application. In this embodiment, the acid concentrate contains 119.737 g/L of sodium chloride (15 mEq/L final concentration in 56 L of dialysate); 204.878 g/L of dextrose (1.5 g/L in final concentration in 56 L); and 32.805 g/L of glacial acetic acid ( 4 mEq/L final concentration in 56 L).

TABLE 2: ACID CONCENTRATE RANGE

Constituent Concentration Ionic Strength

(g/L) (mEq/L)*

NaCl 79.244-158.489 10 - 20 (Na⁺)

KC1 0.000-40.441 0 - 4 (K⁺)

CaCl₂.2H₂O 0.000-34.888 0.00 - 3.50 (Ca⁺)

MgCl₂.6H₂O 6.893-20.680 0.5 - 1.5 (Mg^{* +})

CH,COOH 0.000-36.643 0 - 4.5 (CH,COO )

Dextrose Anhydrous 0-339.000 NA

Conductivity Range 2-3 mS/cm NA

* when diluted in a batch tank with 135.6 times water

The desired concentration of potassium, calcium and magnesium ions in the acid concentrate varies from patient to patient. Generally, the amount of potassium chloride is present in an amount ranging between about 0.00 g and about 40.441 g/L of acid concentrate. The amount of calcium chloride (dihydrate form, CaCl₂.2H₂O) generally ranges between about 0.00 and about 34.888 g/L of acid concentrate. The amount of magnesium chloride (hexahydrate form, MgCl₂.6H₂O) generally ranges between about 6.893 and about 20.68 g/L of acid concentrate. At the aforementioned concentrations, a stable acid concentrate is produced which can be shipped and stored for prolonged periods at a broad range of temperatures, including temperatures ranging between about -10 to -20F, without freezing solid or precipitating out.

While the chloride salts of sodium, potassium, calcium and magnesium are preferred in practicing this invention, it will be understood by the practitioner that other water soluble physiologically acceptable salts of sodium, potassium, calcium and magnesium ions may be used to replace all or part of the corresponding chloride salts. Suitable, but non-limiting, salts include sulfates, carbonates, phosphates, acetates, lactates, and gluconates. If desired, hydrochloric acid may also be used to replace all or part of the acetic acid employed in the acid concentrate.

The bicarbonate concentrate of the invention includes an admixture of sodium chloride and sodium bicarbonate in a predetermined ratio. The bicarbonate concentrate includes sodium chloride in an amount ranging between about 217.6 and about 358.4 g and sodium bicarbonate in an amount ranging between about 143.5 and about 204.7 g per unit. Admixture of the bicarbonate concentrate batch unit with any of the acid concentrate batch units of the invention in an appropriate amount of water will result in a physiologically acceptable dialysate solution. TABLE 3: BICARBONATE POWDER RANGE

Constituent Quantity of Ionic Strength dry powder in (mEq/L)* gms per bottle

NaCl 217 6-358 4 1 10-140 (Na⁺)

NaHCOj 143.5-204 7 30 5 - 43.5 (HCO3^T)

Conductivity Range 10 5-12 7 NA mS/cm

* when diluted in a batch tank with 56 liters of water

In practicing this invention, both the acid concentrate and the bicarbonate concentrates of the invention are preferably in the form of physically discrete units suitable as unitary dosages for each dialysis session, each unit containing a predetermined quantity of the various constituents such when combined with water results in a batch dialysate formulation having the desired concentrations of constituents The unit dosage forms are preferably contained in prepackaged sealed unit dose containers or vessels such as the one descπbed in the Treu et al. patent application seπal no. 08/660,694, filed June 5, 1996, which is incorporated by reference herein in its entirety and can be assembled in kit form for one or more dialysis sessions The vessels descπbed in the Treu et al. patent application are especially designed for patient use and are particularly advantageous for use in conjunction with the home dialysis machine described in the above-referenced Kenley et al patent application However, the present dialysate chemical formulation invention is of course applicable to other vessel designs and machines. There are a number of advantages that can be obtained from the distribution of chemicals in the two concentrate bottles according to the present invention. First, patient safety is assured in batch systems that employ the concentrates of the present invention. For instance, the conductivity of the acid concentrate of the invention generally ranges between about 2-3 mS/cm while the bicarbonate concentrate of the invention generally ranges about 10.5 to 12.7 mS/cm. The combined conductivity ranges between about 12.8 to 15 mS/cm. If two acid concentrate bottles are accidently mixed, the final conductivity will be below 12.8. Similarly, accidental mixing of two bicarbonate concentrate bottles will result in a combined conductivity that exceeds 15 mS/cm. In either case, batch systems that measure conductivity of a dialysate solution prior to initiation of the dialysis procedure will not start the dialysis procedure. Also, batch machines are generally designed to compare the actual conductivity with the prescribed one within +1-5% . If the contents of any of the bottle did not mix in the final solution, the loss of conductivity will be indicated and dialysis procedure will also be halted.

Ordinarily, the conductivity level of dialysate solution resulting from the mixing of vessels containing the acid and bicarbonate concentrates in the batch tank would fall within the expected aforementioned range. No safety alarm will sound and the dialysis session would proceed uneventfully. Inadvertent mixing of two like vessels, e.g. , two acid concentrate vessels or two bicarbonate concentrate vessels, in a batch system, however, would result in a conductivity that exceeds the expected range and thus triggering the alarm and preventing initiation of the dialysis session. In the event that the alarm system fails and the dialysis session does proceed, the patient would not suffer from any permanent harmful result as the conductivity of the dialysate solution formed from the inadvertent mixing of like vessels would still fall within a physiologically acceptable range due to the distribution of sodium chloride between the two vessels as described herein.

Second, the distribution of the chemicals in the acid and bicarbonate concentrates of the invention results in a minimum total volume and weight of concentrates per given volume of final dialysate compared with current commercial packages available. Conventional dialysis systems such as the ones produced by Baxter and Fressenius generally require 3.43 liters of acid and 6.23 liters of bicarbonate concentrate for one 4-hour dialysis treatment. Since a daily dialysis session is typically for 90 minutes, conventional system volumes required for daily dialysis are 1.29 and 2.34 liters, respectively. In contrast, the present invention can provide a total concentrate volume of as little as 0.9 liters (2 X 450 mL bottle) versus a conventional system of 3.63 liters (1.29 L+ 2.34 L). In other words, the acid and bicarbonate concentrates of the invention are about 3 to 4 (3.63/0.9) times more compact in terms of volume compared to conventional systems. Moreover, the nearly saturated acid concentrate provides protection against freezing and dextrose recrystal zation, a common problem found in conventional acid

concentrate formulations.

Third, the distribution of the chemicals in the acid and bicarbonate concentrates of the invention results in greater control and accuracy of sodium and chloride ion concentrations in the dialysate. One of the problems with the conventional systems is maintaining high level accuracy for sodium and chloride ions Many physicians prefer +1-2% for these ions. Since the conventional systems involve making a concentrate for sodium bicarbonate (with or without sodium chloride) and then subsequently dilute to final volume, high accuracy cannot be obtained. The concentrate formulations of the present invention are designed to have only small portions of sodium chloride in acid concentrate and have all the rest of sodium in powder from which is diluted directly. By shifting most of the sodium ions to dry powder, it is now possible to achieve +1- % accuracy of 90% of sodium chloride and 100% of sodium bicarbonate in the dialysate. Moreover, it is easy to control weights of dry powder components in the concentrate (+/-1 %) formulations, thus allowing much higher degree of accuracy in the final solution. Finally, both the acid and bicarbonate concentrates of the invention occupy nearly equal volumes and this advantageously allows for identical container design, thus reducing costs of molds and manufacturing processes. Furthermore, identical container design makes it easier for the manufacturer as well as for the user. Since the connection to the machines are identical and mix-up eliminated by color coding, electronic button checking and conductivity assurance, the use of the acid and bicarbonate concentrates of the invention for prepare batch dialysate provide the highest degree of quality assurance and safety to the patients.

In the example below, a procedure is described using a home dialysis machine for preparing a batch dialysate. Tables are also provided which list representative acid and bicarbonate concentrate formulations as well as batch dialysate formulations prepared by various combinations of the two concentrates. The selection of a particular combination of acid concentrate and bicarbonate concentrate to prepare a 56 L batch of a dialysate formulation having a desired balance of electrolytes is largely dependent on the patient's condition and health needs, and will be prescribed by a physician. The resulting batch of dialysate prepared by mixing the two components in water and diluting the solution to 56 L does not require any further manipulations such as pH adjustment. The concentrate containers are designed to provide chemicals for batch volumes ranging from 40 liters to 60 liters. U

EXAMPLE 1 : PREPARATION OF BATCH DIALYSATE

All chemical reagents employed in preparing the concentrates are USP grade unless otherwise indicated.

(a) Preparation of batch quantity acid concentrate unit. In making the acid concentrate, dextrose is dissolved in a predetermined amount of water with continuous stirring at room temperature, e.g. 70 F. Thereafter, the remaining salts and acetic acid are slowly added to the stirπng solution and the solution volume is raised to a final volume, e.g. , 410 mL, with appropriate amounts of water to produce the acid concentrate. If desired, the concentrate may be sterilized by filtration through a sterile 0.2 micron filter or by autoclaving. The acid concentrate is then poured into a batch quantity vessel such as the one described in the above- referenced Treu et al. application, and the vessel sealed.

(b) Preparation of batch quantity dry bicarbonate unit. In making the dry bicarbonate concentrate, 288.042 grams of NaCl are thoroughly mixed with 183.478 grams of NaHCCv The resulting 471.519 gram powder mixture is then placed into a batch quantity vessel such as the one described in the above-referenced Treu et al. application, and the vessel sealed.

Alternatively, the two salts are simply added to the batch quantity vessel and sealed. No additional mixing in the vessel is required because both of them are completely dissolved in the dialysate tank.

(c) Preparation of batch dialysate. A 56 liter dialysate chemical solution tank is installed in a dialysis machine. The tank has a chemical loading platform that acts as a means for receiving the dialysate chemicals and for introducing the chemicals into the tank. The tank is filled up to the level of the chemical loading platform, or roughly 50 percent of capacity. The chemical loading platform has a slanted shelf which is in fluid communication with the interior of the tank. The contents of the vessels containing the batch quantity dry bicarbonate chemicals and the batch quantity liquid acid concentrate are gradually released from the vessels by gravity and are deposited onto the slanted shelf of the loading platform. The vessels can be either manually opened or automatically opened (in the manner described in the above-referenced Treu et al. application), depending on the construction of the tank and loading platform. A nozzle sprays reverse-osmosis filtered water onto the slanted shelf to disperse the chemicals into the interior of the tank. The tank is then filled completely with RO water. The solution is mixed by swirling the fluid in the tank, accomplished by introducing the RO water into the bottom of the tank generally parallel to the side of the tank, and by withdrawing solution from the bottom of the tank and reintroducing it at the top of the tank in a turbulent manner with a sprayer.

The flow path of the dialysate when it is withdrawn from the bottom of the tank and reintroduced at the top of the tank includes a conductivity sensor. The conductivity sensor sends conductivity readings to a central processing unit controlling the operation of the machine.

When the conductivity readings meet an expected value for the particular dialysate formulation, the solution is deemed mixed and the mixing process ceases. The dialysis session then commences according to well known techniques.

Table 4 lists representative formulation ranges for different liquid acid concentrates. All quantities are in grams/L, with a total volume in each bottle being 290 to 440 ml. The quantities are for dilution to a 40 to 60 liter batch of dialysate. The particular formulation to be used for preparation of a batch of dialysate depends upon the medical condition of the patient, and will be prescnbed by a physician The conductivity of acid concentrate when diluted to the required volume by itself (without powder) will range between 2-3 mS/cm.

Table 5 shows representative formulation ranges for different batch quantity dry bicarbonate chemicals formulations The dialysate solution is prepared by mixing one of the formulations from Table 4 with one of the formulations from Table 5 As was the case with

Table 4, the particular formulation to be selected from Table 5 depends on the medical condition of the patient, and will be prescribed by the patient's physician Also, the formulation is for dilution to a 56 liter batch of dialysate Again, the precise quantities of the salt and bicarbonate may vary depending on the final volume of dialysate that is prepared Since there are 14 representative acid concentrate formulations and 4 representative bicarbonate concentrate formulations, there are 56 possible final dialysate combinations as listed in Tables 6, 7, 8 and 9 Table 6 consists of a combination of all of the fourteen acid concentrate formulations with the bicarbonate concentrate PI Table 7 consists of a combination of all of the fourteen acid concentrate formulations with the bicarbonate concentrate P2 Table 8 consists of a combination of all of the fourteen acid concentrate formulations with the bicarbonate concentrate P3. Table 9 consists of a combination of all of the fourteen acid concentrate formulations with the bicarbonate concentrate P4.

Tables 10-13 list the dialysate ionic formulations resulting from the 56 possible combinations of acid concentrate and bicarbonate concentrate, when diluted to 56 liters final volume with reverse osmosis filtered water The conductivity of bicarbonate chemicals formulation when diluted to the required volume by itself (without acid) will range 10.5-12.7 mS/cm. It will be understood that the example described above is by way of illustration and is not meant to limit the scope of the present invention. It is expected that certain changes, substitutions and modifications of the present invention will be apparent to a person skilled in the an to which the present invention pertains, without depaπing from the spirit of the present invention.

TABLE 4: FORMULATIONS TABLE FOR BATCH OUANTITY ACID CONCENTRATE

Code Dextrose Acetic Water @

NaCl KC1 CaCK. MgCl,. Mono Acid 71 °F 2H,O 6H₂O

LI 49.092 8.351 1 1.321 5.693 92.400 13.45 307.317

L2 49.092 8.351 1 1.321 4.270 92.400 13.45 307.988

L3 49.092 8.351 9.468 5.693 92.400 13.45 308.190

L4 49.092 8.351 9.468 4.270 92.400 13.45 308.861

L5 49.092 8.351 14.408 5.693 92.400 13.45 305.862

L6 49.092 12.526 1 1.321 5.693 92.400 13.45 305.349

L7 49.092 12.526 9.468 5.693 92.400 13.45 306.222

L8 49.092 12.526 14.408 5.693 92.400 13.45 303.894

L9 49.092 4.175 11.321 5.693 92.400 13.45 309.285

L10 49.092 4.175 9.468 5.693 92.400 13.45 310.158

Ll l 49.092 4.175 14.408 5.693 92.400 13.45 307.83

L12 49.092 0.00 1 1.321 5.693 92.400 13.45 31 1.253

L13 49.092 8.351 4. 1 17 5.693 92.400 13.45 310.712

L14 49.092 8.351 1 1.321 8.540 92.400 13.45 305.975

Max. 49.092 12.526 14.408 8.540 92.400 13.45 31 1.253

Min. 49.092 0.000 4.1 17 4.270 92.400 13.45 303.894

Ave. 49.092 8.649 10.938 5.693 92.400 13.45 307.778

Note: All quantities in g/bottle, final volume 410 ml. Above formulations are for dilution to 56 liters batch system. TABLE 5: FORMULATIONS TABLE FOR BATCH OUANTITY BICARBONATE CONCENTRATE

Net Final Wt.

Code # NaCl (g) NaHCO, (g) ⁽g)

PI 288.042 183.478 471.519

P2 274.949 183.478 458.427

P3 274.949 202.296 477.245

P4 261.856 202.296 464.152

Max. 288.042 202.296 477.245

Min. 261.856 183.478 458.427

Ave. 274.949 192.887 467.836

Note: All quantities in g/bottle. Above formulations are for dilution to 56 liters batch system.

TABLE 6: FORMULATIONS TABLE FOR FINAL DIALYSATE

Combination of all acid concentrate formulations with bicarbonate formulation PI. Example combination (PI +L4 + water for dilution) = D104

Dialysate g/l g/l g/l g/l g/l g/l g/l g/l

Formula CaC MgCl;. Acetic ft NaCl KCI 2H_:0 6H_:0 NaHCO., acid Dextrose Solutes

D101 6.019 0.149 0.202 0.102 3.276 .240 1.650 11.639

DI02 6.019 0.149 0.202 0.076 3.276 .240 1.650 11.614

D103 6.019 0.149 0.169 0.102 3.276 .240 1.650 11.606

D104 6.019 0.149 0.169 0.076 3.276 .240 1.650 11.581

D105 6.019 0.149 0.257 0.102 3.276 .240 1.650 11.694

D106 6.019 0.224 0.202 0.102 3.276 .240 1.650 11.714

D107 6.019 0.224 0.169 0.102 3.276 .240 1.650 11.681

D108 6.019 0.224 0.257 0.102 3.276 .240 1.650 11.769

D109 6.019 0.075 0.202 0.102 3.276 .240 1.650 11.565

DUO 6.019 0.075 0.169 0.102 3.276 .240 1.650 11.532

Dill 6.019 0.075 0.257 0.102 3.276 .240 1.650 11.620

D1I2 6.019 0.000 0.202 0.102 3.276 .240 1.650 11.490

D113 6.019 0.149 0.074 0.102 3.276 .240 1.650 11.511

D114 6.019 0.149 0.202 0.153 3.276 .240 1.650 11.690 TABLE 7: FORMULATIONS TABLE FOR FINAL DIALYSATE

Combination of all acid concentrate formulations with bicarbonate formulation P2. Example combination (P2+L01 + water for dilution) = D201

Dialysate g/l g/l g/l g/l g/l g/l g/l g/i

Formula CaCK. MgCl;. Acetic ft NaCl KC1 2H.O 6H,0 NaHCO, acid Dextrose Solutes

D201 5.787 0.149 0.202 0. 102 3.276 .240 1.650 1 1.405

D202 5.787 0. 149 0.202 0.076 3.276 .240 1.650 1 1.380

D203 5.787 0. 149 0.169 0.102 3.276 .240 1.650 1 1.372

D204 5.787 0.149 0. 169 0.076 3.276 .240 1.650 11.347

D205 5.787 0.149 0.257 0. 102 3.276 .240 1.650 1 1.461

D206 5.787 0.224 0.202 0.102 3.276 .240 1.650 1 1.480

D207 5.787 0.224 0.169 0.102 3.276 .240 1.650 11.447

D208 5.787 0.224 0.257 0.102 3.276 .240 1.650 11.535

D209 5.787 0.075 0.202 0.102 3.276 .240 1.650 11.331

D210 5.787 0.075 0. 169 0.102 3.276 .240 1.650 1 1.298

D211 5.787 0.075 0.257 0.102 3.276 .240 1.650 11.386

D212 5.787 0.000 0.202 0.102 3.276 .240 1.650 11.256

D213 5.787 0.149 0.074 0.102 3.276 .240 1.650 11.277

D214 5.787 0.149 0.202 0.153 3.276 .240 1.650 1 1.456

TABLE 8: FORMULATIONS TABLE FOR FINAL DIALYSATE

Combination of all acid concentrate formulations with bicarbonate formulation P3. Examples combination (P3 + L12 -ι-water for dilution) = D312

Dialysate g/i g/l g/l g/l g/l g/i g/l g/l

Formula CaCI;. MgCl;. Acetic ft NaCl KCI 2H;0 6H,0 NaHCO, acid Dextrose Solutes

D301 5.787 0.149 0.202 0.102 3.612 .240 1.650 1 1.741

D302 5.787 0.149 0.202 0.076 3.612 .240 1.650 1 1.761

D303 5.787 0.149 0.169 0. 102 3.612 .240 1.650 1 1.708

D304 5.787 0.149 0.169 0.076 3.612 .240 1.650 11.683

D305 5.787 0.149 0.257 0.102 3.612 .240 1.650 1 1.797

D306 5.787 0.224 0.202 0.102 3.612 .240 1.650 1 1.816

D307 5.787 0.224 0.169 0.102 3.612 .240 1.650 11.783

D308 5.787 0.224 0.257 0. 102 3.612 .240 1.650 11.871

D309 5.787 0.075 0.202 0.102 3.612 .240 1.650 11.667

D310 5.787 0.075 0. 169 0.102 3.612 .240 1.650 11.634

D311 5.787 0.075 0.257 0.102 3.612 .240 1.650 11.722

D312 5.787 0.000 0.202 0.102 3.612 .240 1.650 11.592

D313 5.787 0.149 0.074 0.102 ^' 3.612 .240 1.650 11.613

D314 5.787 0.149 0.202 0.153 3.612 .240 1.650 1 1.792

TABLE 9: FORMULATIONS TABLE FOR FINAL DIALYSATE

Combination of all acid concentrate formulation*, with bicarbonate formulation P4 Example combination (P4 + L1 + water for dilution) = D401

Dialysate g/i g/l g/l g/i g/l g/l g/l g/l

Formula CaCI,. MgCl,. Acetic ft NaCl KCI 2H,0 6H,θ^" NaHCO, acid Dextrose Solutes

D401 5.553 0.149 0.202 0.102 3.612 .240 1.650 11.508

D402 5.553 0.149 0.202 0.076 3.612 .240 1.650 1 1.482

D403 5.553 0.149 0. 169 0.102 3.612 .240 1.650 1 1.475

D404 5.553 0. 149 0.169 0.076 3.612 .240 1.650 11.449

D405 5.553 0.149 0.257 0.102 3.612 .240 1.650 1 1.563

D406 5.553 0.224 0.202 0.102 3.612 .240 1.650 1 1.582

D407 5.553 0.224 0.169 0.102 3.612 .240 1.650 1 1.549

D408 5.553 0.224 0.257 0.102 3.612 .240 1.650 11.637

D409 5.553 0.075 0.202 0.102 3.612 .240 1.650 1 1.433

D410 5.553 0.075 0.169 0.102 3.612 .240 1.650 1 1.400

D411 5.553 0.075 0.257 0.102 3.612 .240 1.650 1 1.488

D412 5.553 0.000 0.202 0.102 3.612 .240 1.650 1 1.359

D413 5.553 0.149 0.074 0.102 3.612 .240 1.650 1 1.379

D414 5.553 0.149 0.202 0.153 3.612 .240 1.650 11.559

Max. 6.019 .224 .257 .153 3.276 .240 1.650 12.156

Min. 5.552 .000 .074 .076 2.940 .240 1.650 10.869

Ave. 5.786 .138 .195 .102 3.108 .240 1.650 1 1.556 TABLE 10: DIALYSATE IONIC FORMULATIONS

Dialysate meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 g/1 comments

Dextrose

Formula monoft Na^* K- Ca" Mg" HC0₃ OAc Cl hydrate

D101 142 2.00 2.75 1.00 35 4 108.75 1.65

D102 142 2.00 2.75 0.75 35 4 108.50 1.65 Min. Mg

D103 142 2.00 2.30 1.00 35 4 108.30 1.65

D104 142 2.00 2.30 0.75 35 4 108.05 1.65 Min. Mg

D105 142 2.00 3.50 1.00 35 4 109.50 1.65

D106 142 3.00 2.75 1.00 35 4 109.75 1.65

D107 142 3.00 2.30 1.00 35 4 109.30 1.65

D108 142 3.00 3.50 1.00 35 4 110.50 1.65 Max. Na, K, Ca

D109 142 1.00 2.75 1.00 35 4 107.75 1.65

DUO 142 1.00 2.30 1.00 35 4 107.30 1.65

Dill 142 1.00 3.50 1.00 35 4 108.50 1.65

D112 142 0.00 2.75 1.00 35 4 106.75 1.65 K Free

D113 142 2.00 1.00 1.00 35 4 107.00 1.65 Min. Ca

D114 142 2.00 2.75 1.50 35 4 109.25 1.65 Max. Na,

Mg

Note: Combination of all acid concentrate formulations with PI. Example combination (Pl+L12+water for dilution) = D112. PI contains 127 meq/L of Na^* and 39 meq/L of HCO₃ TABLE 11 : DIALYSATE IONIC FORMULATIONS

Dialysate meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 g/1 comments

Dextrose

Formula monoft Na^* K^* Ca^{* *} Mg^{* "} HCO, OAc Cl hydrate

D201 138 2.00 2.75 1.00 35 4 104.75 1.65

D202 138 2.00 2.75 0.75 35 4 104.50 1.65 M . Mg

D203 138 2.00 2.30 1.00 35 4 104.30 1.65

D204 138 2.00 2.30 0.75 35 4 104.05 1.65 Min. Mg

D205 138 2.00 3.50 1.00 35 4 105.50 1.65

D206 138 3.00 2.75 1.00 35 4 105.75 1.65

D207 138 3.00 2.30 1.00 35 4 105.30 1.65

D208 138 3.00 3.50 1.00 35 4 106.50 1.65

D209 138 1.00 2.75 1.00 35 4 103.75 1.65

D210 138 1.00 2.30 1.00 35 4 103.30 1.65

D211 138 1.00 3.50 1.00 35 4 104.50 1.65

D212 138 0.00 2.75 1.00 35 4 102.75 1.65 K Free

D213 138 2.00 1.00 1.00 35 4 103.00 1.65 Mm. Ca

D214 138 2.00 2.75 1.50 35 4 105.25 1.65 Max. Mg

Note: Combination with all acid concentrate formulations with P2. PI contains 123 meq/L of Na* and 39 meq/L of HCO₃ ^' TABLE 12: DIALYSATE IONIC FORMULATIONS

Dialysate meq/1 meq/| meq/1 meq/1 meq/1 meq/1 meq/1 g/l comments

Dextrose

Formula monoft Na^* K- Ca" Mg^{* *} HCO, OAc Cl hydrate

D301 142 2.00 2.75 1 00 39 4 104.75 1.65

D302 142 2.00 2.75 0 75 39 4 104.50 1.65 M . Mg

D303 142 2.00 2.30 1.00 39 4 104.30 1.65

D304 142 2.00 2.30 0 75 39 4 104.05 1.65 Mtn. Mg

D305 142 2.00 3.50 1.00 39 4 105.50 1.65

D306 142 3.00 2.75 1.00 39 4 105.75 1.65

D307 142 3.00 2.30 1.00 39 4 105.30 1.65

D308 142 3.00 3.50 1.00 39 4 106.50 1.65 Max. Na, K, Ca, HCO,

D309 142 1.00 2 75 1 00 39 4 103.75 1.65

D310 142 1.00 2.30 1 00 39 4 103.30 1.65

D311 142 1.00 3.50 1.00 39 4 104.50 1.65

D312 142 0.00 2.75 1.00 39 . 4 102.75 1.65 K Free

D313 142 2.00 1.00 1.00 39 4 103.00 1.65 Mm. Ca

D314 142 2.00 2.75 1.50 39 4 105.25 1.65 Max. Mg, HCO,

Note: Combination of all acid concentrate formulations with P3. P3 contains 127 meq/L of Na* and 43 meq/L HCO₃ ^' TABLE 13: DIALYSATE IONIC FORMULATIONS

Dialysate meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 meq/1 g/i comments

Dextrose

Formula monoft Na^* K^* Ca" Mc ^" HCO, OAc Cl hydrate

D401 138 2.00 2.75 1.00 39 4 100.75 1.65

D402 138 2.00 2.75 0.75 39 4 100.50 1.65 Mm. Mg

D403 138 2.00 2.30 1.00 39 4 100.30 1.65

D404 138 2.00 2.30 0.75 39 4 100.05 1.65 M . Mg

D405 138 2.00 3.50 1.00 39 4 101.50 1.65

D406 138 3.00 2.75 1.00 39 4 101 .75 1 .65

D407 138 3.00 2.30 1.00 39 4 101.30 1.65

D408 138 3.00 3.50 1.00 39 4 102.50 1.65

D409 138 1.00 2.75 1.00 39 4 99.75 1.65

D410 138 1.00 2.30 1.00 39 4 99.30 1.65

D411 138 1.00 3.50 1.00 39 4 100.50 1.65

D412 138 0.00 2.75 1 .00 39 4 98.75 1.65 K Free

D413 138 2.00 1.00 1.00 39 4 99.00 1.65 Mm. Ca

D414 138 2.00 2.75 1.50 39 4 101.25 1.65 Max. Mg

Note: Combination of all acid concentrate formulations with P4. P4 contains 123 meq/L of Na* and 43 meq/L HCO₃ ^'

Claims

WE CLAIM:

1. A pre-packaged vessel containing a dialysate concentrate for use in preparing a batch of dialysate composing:

(a) sodium chlonde in an amount sufficient to provide a final batch concentration ranging between about 5.289 and about 6 984 g/L; (b) potassium chloride in an amount sufficient to provide a final batch concentration up to about 0.298 g/L,

(c) calcium chlonde dihydrate in an amount sufficient to provide a final batch concentration up to about 0 258 g/L;

(d) magnesium chlonde hexahydrate in an amount sufficient to provide a final batch concentration ranging between about 0.057 and about 0.152 g/L;

(e) dextrose in an amount sufficient to provide a final batch concentration of about 2.50 g/L;

(f) sodium acetate in an amount sufficient to provide a final batch concentration of about 0.612 g/L; and (g) a predetermined amount of water.

2. A pre-packaged vessel containing an aqueous acid concentrate for use in preparing a batch of dialysate compnsing-

(a) between about 79.244 and about 158.489 g/L of sodium chlonde;

(b) between about 0 and about 40 441 g/L of potassium chlonde;

(c) between about 0 and about 34.888 g/L of calcium chloride dihydrate; (d) between about 6.893 and about 20.680 g/L magnesium chlonde hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose; and

(f) between about 0 and about 36.643 g/L of acetic acid.

3 The pre-packaged vessel according to claim 1 , wherein water is present in sufficient amount to produce a final concentrate volume ranging between about 290 and about 440 L final volume.

4. The prepackaged vessel of claim 1 , wherein said quantities of ingredients (a) -(g) are selected from one of the formulations defined in Table 4

5. A pre-packaged vessel containing a dry bicarbonate concentrate for use in prepanng a batch of dialysate compnsing

(a) between about 217.6 and about 358 4 g of sodium chloride, and

(b) between about 143.5 and about 204 7 g of sodium bicarbonate.

6. The pre-packaged vessel of claim 5, wherein said quantities of ingredients (a) and (b) are selected from one of the formulations defined in Table 5.

7. A kit for prepanng a batch size quantity of dialysate comprising: (i) an acid concentrate comprising:

(a) between about 79.244 and about 158.489 g/L of sodium chloride;

(b) between about 0 and about 40.441 g/L of potassium chloride; (c) between about 0 and about 34.888 g/L of calcium chlonde dihydrate;

(d) between about 6.893 and about 20.680 g/L magnesium chlonde hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose;

(f) between about 0 and about 36.643 g/L of acetic acid;

(g) water in sufficient amount to bring up to about 290 - 440 mL final volume; (ii) a bicarbonate concentrate comprising:

(a) between about 271.6 and about 358.4 g of sodium chloride;

(b) between about 143.5 - 204.7 g of sodium bicarbonate; and

(iii) batch quantity containers for separating said acid concentrate and said dry mixture.

8. A method for preparing batch size quantities of dialysate compnsing: a) loading a first container holding a batch quantity of aqueous acid concentrate and a second container holding a batch quantity of dry bicarbonate concentrate into a dialysate preparation tank; b) admixing the acid concentrate and bicarbonate concentrated in a predetermined amount of water in said dialysate preparation tank; and c) adding a sufficient amount of water to said tank to prepare a batch of dialysate.

9. The method according to claim 8, wherein said acid concentrate comprises:

(a) between about 79.244 and about 158.489 g/L of sodium chloride;

(b) between about 0 and about 40.441 g/L of potassium chloride;

(c) between about 0 and about 34.888 g/L of calcium chloride dihydrate;

(d) between about 6.893 and about 20.680 g/L magnesium chloride hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose; and

(f) between about 0 and about 36.643 g/L of acetic acid.

10. The method according to claim 8, wherein said bicarbonate concentrate comprises:

(a) between about 217.6 and about 358.4 g of sodium chloride; and

(b) between about 143.5 and about 204.7 g of sodium bicarbonate.

11. A kit for preparation of a batch of dialysate solution comprising a) a first vessel containing a batch quantity of liquid acid dialysate concentrate, said liquid acid dialysate concentrate comprising sodium chloride and having a conductivity ranging from between about 2 and about 3 mS/cm; and b) a second vessel containing a batch quantity of dry bicarbonate dialysate concentrate, said dry bicarbonate dialysate concentrating comprising sodium chloride and having a conductivity ranging from between about 12.8 and about 15 mS/cm; said batch of dialysate solution comprising the mixture of the contents of said first vessel and said second vessel with sufficient water in a batch quantity tank to form a suitable volume for dialysis of a patient, wherein the inadvertent mixture of two of said first vessels or said second vessels with water filling said batch quantity tank results in a solution having a conductivity value which is physiologically acceptable to a patient.

12. The kit according to claim 1 1 , wherein (0 said acid concentrate comprises: (a) between about 79 244 and about 158 489 g/L of sodium chlonde;

(b) between about 0 and about 40 441 g/L of potassium chlonde,

(c) between about 0 and about 34.888 g/L of calcium chlonde dihydrate,

(d) between about 6.893 and about 20.680 g/L magnesium chlonde hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose; (f) between about 0 and about 36.643 g/L of acetic acid,

(ii) said bicarbonate concentrate compnses-

(a) between about 271 6 and about 358 4 g of sodium chlonde; and

(b) between about 143.5 - 204.7 g of sodium bicarbonate

13. The kit according to claim 12, wherein said quantities of ingredients (I) (a) -(g) are selected from one of the formulations defined in Table 4

14 The kit according to claim 12, wherein said quantities of ingredients (n) (a) and (b) are selected from one of the formulations defined in Table 5

15. The kit according to claim 1 1 , wherein the volume of said first and second vessels range from between about 290 to 440 L

16. The kit according to claim 1 1 , wherein the volume of said first and second vessels are the same.

17. The kit according to claim 1 1 , wherein the amount of said sodium chloride in said acid concentrate is sufficient to prevent freezing of the acid concentrate at -20°F.

18. The kit according to claim 1 1 , wherein the acid concentrate is sufficiently saturated so as to prevent recrystallization of dextrose.

19. A pre-packaged vessel containing an aqueous acid concentrate for use in conjunction with a bicarbonate concentrate for preparing a batch of dialysate in a batch quantity tank comprising:

(a) between about 79.244 and about 158.489 g/L of sodium chloride; (b) between about 0 and about 40.441 g/L of potassium chloride;

(c) between about 0 and about 34.888 g/L of calcium chloride dihydrate;

(d) between about 6.893 and about 20.680 g/L magnesium chloride hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose; and

(f) between about 0 and about 36.643 g/L of acetic acid; said acid concentrate having a conductivity ranging from between about 2.0 and about 3.0 mS/cm, wherein the inadvertent mixture of two of said vessels with water filling said batch quantity tank results in a dialysate solution having a conductivity value that is physiologically acceptable to a patient.

20. The pre-packaged vessel according to claim 19, wherein said vessel has a volume ranging from between about 290 to 440 L.

21. A pre-packaged vessel containing a dry bicarbonate concentrate for use in conjunction with an acid concentrate for preparing a batch of dialysate comprising: (a) between about 217.6 and about 358.4 g of sodium chloride; and

(b) between about 143.5 and about 204.7 g of sodium bicarbonate; said bicarbonate concentrate having a conductivity ranging from between about 12.8 and about 15 mS/cm, wherein the inadvertent mixture of two of said vessels with water filling said batch quantity tank results in a dialysate solution having a conductivity value which is physiologically acceptable to a patient.

22. The pre-packaged vessel according to claim 21 , wherein said vessel has a volume ranging from between about 290 to 440 mL.

23. A kit for preparing a batch size quantity of dialysate solution comprising: (i) an acid concentrate comprising: (a) between about 79.244 and about 158.489 g/L of sodium chloride;

(b) between about 0 and about 40.441 g/L of potassium chloride;

(c) between about 0 and about 34.888 g/L of calcium chloride dihydrate;

(d) between about 6.893 and about 20.680 g/L magnesium chloride hexahydrate;

(e) between about 0 and about 339.00 g/L of dextrose; (f) between about 0 and about 36.643 g/L of acetic acid; (g) water in sufficient amount to bring up to about 290 and about 440 mL final volume; (ii) a bicarbonate concentrate comprising:

(a) between about 271.6 and about 358.4 g of sodium chloride; (b) between about 143.5 - 204.7 g of sodium bicarbonate; and

(iii) batch quantity containers for separating said acid concentrate and said dry mixture, said containers having volumes ranging between about 290 and about 440 mL; said batch of dialysate solution comprising the mixture of said acid concentration and said bicarbonate concentrate with sufficient water in a tank to form a suitable volume for dialysis of a patient, wherein the inadvertent mixture of two of said acid concentrate or bicarbonate concentrate with water filling said batch quantity tank results in a solution having a conductivity value which is physiologically acceptable to a patient.

24. The kit according to claim 23, wherein said volumes of said batch quantity containers are the same.