Preparation of dry dialysate products

This invention is directed to dry, free-flowing, stable readily soluble, non-caking, particulate solid products which are readily soluble in water and which are useful for preparing solutions for use in hemodialysis and peritoneal dialysis and to the preparation of these granular products.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to hemodialysis and peritoneal dialysis. 
More particularly, this invention relates to: (a) dry, free-flowing, 
stable, dust-free, non-caking, granular products or compositions which are 
readily soluble in water and which are suitable and useful for preparing 
solutions for use in hemodialysers and in peritoneal dialysis and (b) to 
the preparation of such granular products. 
2. Description of the Prior Art 
Hemodialysers, which are known as "artificial kidneys" and which are also 
referred to as "dialysers", are used in the care of patients suffering 
from renal deficiencies because of disease or injury. Such devices remove 
waste matter (waste products of metabolism) from blood by means of a 
semipermeable membrane and a specially formulated solution which extracts 
the wast matter through the semi-permeable membrane. In hemodialysis, 
blood is removed from a patient's body and circulated through a dialyser 
to remove waste products from the blood. On the other hand, in peritoneal 
dialysis, a dialysis solution is injected into the patient's abdominal 
cavity where wastes pass through the membranes of the patient's body into 
the dialysis solution which is subsequently drained from the abdominal 
cavity. 
Solutions used in hemodialysers or in peritoneal dialysis generally 
contain, as major components, dextrose (if required by the patient), 
sodium chloride and sodium acetate and/or sodium bicarbonate (the sodium 
acetate or sodium bicarbonate serves as an alkalizing agent), along with 
smaller amounts of calcium, magnesium and sometimes potassium as chlorides 
and other water soluble physiologically acceptable salts, such as small 
amounts of lactates or gluconates if required by the patient. These 
materials (e.g., lactates and gluconates) must not be present in amounts 
sufficient to precipitate calcium or magnesium ions. Potassium acetate and 
gluconates and lactates of sodium, potassium, magnesium or calcium, if 
present, also serve as alkalizing agents. 
Peritoneal dialysis is described in the June 2, 1980 issue of Barrons at 
pages 35 and 42. 
To date, commercial practice has been largely limited to supplying 
hemodialysis and peritoneal dialysis solutions in the form of liquid 
concentrates, although it has been recognized for years that a stable dry 
product capable of being readily and completely dissolved in water would 
have convenience and handling cost advantages. Such a dry product is 
taught by U.S. Pat. No. 3,560,380. Products described therein are made by 
combining a specially prepared spray-dried sodium acetate, having a 
moisture content of less than 0.2% by weight, with ordinary anhydrous 
grades of other materials to form a simple physical mixture. A further 
provision is that the total moisture content of the composition does not 
exceed 0.75%. Product stability against caking and discoloration is said 
to result from the low water content of the spray-dried sodium acetate. 
Such products have not obtained broad acceptance in the marketplace, 
possibly because of the small particle size of the spray-dried materials. 
Spray-dried sodium acetate is dusty and, consequently, has unpleasant 
handling characteristics. 
A prior art dialysis solution based on bicarbonate is described in a 
bulletin entitled "SB-600 Bicarbonate Batch Formula", published by Renal 
Systems, Inc., 14905 28th Ave. North, Minneapolis, Minn. 55441. The 
precursor of said solution is provided in two parts. These are (a) a first 
part comprising 3.42 liters of an "acid based concentrate", and (b) a 
second part which is 393 g of sodium bicarbonate. The first part is 
diluted to slightly less than 120 liters with water, the second part (the 
sodium bicarbonate) is admixed in approximately one quart of water and 
added to the aforesaid diluted first part. The resulting mixture is 
diluted with water to 120 liters to form a bicarbonate based dialysis 
solution which will be referred to as "Solution A". Said Solution A 
contains: 
______________________________________ 
MEq/l Eq/l gms/l 
______________________________________ 
Sodium 140 or 0.140 or 0.14 .times. 23 
= 3.22 
Calcium 3.5 or 0.0035 
##STR1## = 0.0701 
Magnesium 
1.5 or 0.0015 
##STR2## = 0.0182 
Chloride 106 or 0.106 or 0.106 .times. 35.45 
= 3.7577 
Bicarbonate 
35 or 0.035 or 0.035 .times. 61 
= 2.1350 
Dextrose 250 or 0.250 or 0.250 .times. 180 
= 45.0 
(C.sub.6 H.sub.12 O.sub.6) 
______________________________________ 
As noted supra, in the above Renal Systems SB-600 Bicarbonate Batch 
Formula, all constituents except the sodium bicarbonate are contained in 
the acid based concentrate as sodium chloride, calcium chloride, magnesium 
chloride and dextrose. 
Other chemicals (e.g., potassium chloride), if required, are added and, if 
necessary, the pH is adjusted to 7.2 to 7.4 after mixing the acid based 
concentrate and the sodium bicarbonate but before using the resulting 
solution. 
It should be noted that the use of sodium bicarbonate comprising dialysate 
solutions is complicated by the fact that calcium and magnesium ions do 
not remain soluble in the presence of concentrated sodium bicarbonate 
solutions. In the presence of water, calcium and magnesium ions tend to 
combine with carbonate present and readily precipitate at low 
concentrations. pH must be closely controlled. 
In the early 1960s (Mion, C. M. et al, "Substitution of Sodium Acetate for 
Sodium Bicarbonate in the Bath Fluid for Hemodialysis", Trans. Am. Soc. 
Artif. Internal Organs 10:110, 1964), sodium acetate was instituted for 
sodium bicarbonate as the fixed base in hemodialysis solutions. This was 
done primarily because the sodium acetate containing solutions were more 
stable in use, whereas the sodium bicarbonate comprising solutions were 
less stable because of the low solubility of calcium and magnesium 
carbonates. It is essential that exact control of various necessary ions 
in the dialysis solution be obtained. The tendency for calcium and 
magnesium carbonates to precipitate at solution use concentrations caused 
the switch in 1964 from sodium bicarbonate as the fixed base to sodium 
acetate. This switch also made possible the use of proportioning pumps to 
handle dialysate concentrates. 
Information is now surfacing indicating that there is "Less 
Dialysis-Induced Morbidity and Vascular Instability with Bicarbonate in 
Dialysate" (U. Graefe et al, March, 1978, Annals of Internal Medicine, 
Vol. 88, No. 3, pages 332-336). It is now evident that bicarbonate in a 
dialysate solution, rather than acetate, is better tolerated by the 
patient. 
SUMMARY OF THE INVENTION 
Sodium Acetate System 
It is an object of the present invention to provide a solid system (a 
granular product) based on the use of sodium acetate as the alkalyzing 
agent which is useful for preparing a solution for use in hemodialysis or 
peritoneal dialysis. Said system is a dry, free-flowing, non-caking, 
chemically homogeneous color-stable, readily water-soluble granular 
product useful for preparing a hemodialysis solution or a peritoneal 
dialysis solution based on sodium acetate as the alkalizing agent. The 
product comprises an intimate admixture of sodium acetate and sodium 
chloride and physiologically acceptable salts of magnesium and calcium, 
for example, magnesium chloride and calcium chloride. If required or 
desired, minor amounts of lactate ions and/or gluconate ions can be 
present. These are usually provided as the sodium salts but can be 
provided as calcium or magnesium salts or as potassium salts if potassium 
ions are included in the granular product. 
Said product is further characterized in that the granules are chemically 
homogeneous since each granule exists as a "micro homogeneous mixture" of 
discrete particles of simultaneously formed mixed small crystals or 
amorphous forms of components. That is to say, each product granule has 
substantially the same chemical composition as any other granule from the 
same lot. The granular product (granules) is preferably in the range of 
-20 to +100 mesh, and is notably dust-free and uniquely rapidly soluble in 
water. The low water content, absence of fines and somewhat open, i.e., 
porous, granular structure mitigates against bulk caking during storage 
and during the solution process. Further, individual components comprising 
the granular products of this invention do not physically separate one 
from the other during handling and storage as is often the case with 
simple mixtures. 
If required or desired, a potassium salt selected from the group consisting 
of (a) potassium chloride, (b) potassium lactate, (c) potassium acetate, 
and (d) potassium gluconate can be included in the granular product. 
Potassium chloride is generally preferred. 
The dry, non-caking, free-flowing, stable, readily soluble, dust-free 
granular sodium acetate system of this invention is heterogeneous in the 
physical sense because the individual granules are aggregates of small 
crystals of the individual salts constituting or comprising the granules. 
However, the granules are homogeneous on a particulate basis (i.e., they 
are chemically homogeneous) because each individual granule contains a 
constant portion of the individual components. Product granules are 
preferably about -20 mesh and +100 mesh. 
Solid masses, e.g., sheets, lumps, large granules, chunks and the like of 
said sodium acetate-alkalyzed system of a specific run (before crushing to 
prepare the final granular product) are chemically homogeneous because 
samples taken from randomly selected portions of such masses have 
substantially the same chemical composition. 
The granular sodium acetate system of this invention is readily soluble 
because a 60 g portion of said product can be completely dissolved in 140 
g of water in a 400 ml beaker at about 20.degree.-30.degree. C. when using 
gentle stirring in less than three minutes. Gentle stirring as used herein 
means stirring with a 1-inch blade in a 400 ml beaker at about 300 RPM. 
It is another object of this invention to provide a method for preparing 
the above-described granular product by a process characterized in that 
salts to be included in the granules comprising the granular product are 
admixed in the presence of water. Said water can be the water of hydration 
of at least one of said salts, or it can be liquid water which is admixed 
with said salts to form a partial or complete solution thereof. The water 
is rapidly vaporized to form a dry solid product which is crushed and 
sized to form product and material for recycling in the process. Each of 
the resulting granules is an intimate admixture of minute particles of 
each component, the components being the above-mentioned salts. 
Sodium Bicarbonate Systems 
It is also an object of the present invention to provide dry free-flowing, 
non-caking, color stable, readily water soluble granular products useful 
for preparing a hemodialysis solution or a peritoneal dialysis solution, 
such solution being based on sodium bicarbonate as the primary alkalizing 
agent. 
In the sodium bicarbonate systems of this invention wherein sodium 
bicarbonate serves as the primary (main) alkalizing agent, the sodium 
bicarbonate is handled as a separate entity and only admixed with the 
other constituents after the complete removal of water from said other 
constituents. 
The sodium bicarbonate systems can contain minor amounts of sodium, 
magnesium, calcium and potassium acetates, lactates and gluconates (or 
mixtures thereof) as secondary (minor) alkalyzing agents. 
In the absence of water, in which materials can dissolve, calcium and 
magnesium salts do not react with sodium bicarbonate to form insoluble 
carbonates. 
Two different sodium bicarbonate system accomplish this object. These are: 
First Sodium Bicarbonate System 
The product of the first sodium bicarbonate system consists essentially of 
a dry, free-flowing, non-caking, chemically homogeneous, color stable, 
readily water-soluble first granular product comprising an intimate 
admixture of sodium chloride and physiologically acceptable ionic salts of 
magnesium and calcium plus, if desired, a minor amount of sodium acetate, 
sodium lactate or sodium gluconate. Said salts of magnesium and calcium 
can have anions selected from the group consisting of: (i) chloride, (ii) 
acetate, (iii) lactate and (iv) gluconate and (v) mixtures thereof. 
Chloride is generally the preferred anion. Said dry first granular product 
is admixed with finely divided (ca. -60 to +200 mesh) anhydrous sodium 
bicarbonate to form a composition which is representative of the first 
sodium bicarbonate system of this invention. 
As with the sodium acetate system, radio frequency (microwave or 
electromagnetic) heating is preferred when preparing granular products of 
the first sodium bicarbonate system, but other heating methods (including 
those using conduction and convection) are operable. 
The granular products of the first sodium bicarbonate system are similar to 
the granular products of the above-discussed sodium acetate system except 
that: (a) sodium bicarbonate is the sole or principal (major) alkalyzing 
agent in the first sodium bicarbonate system while sodium acetate is the 
sole or principal alkalyzing agent in the granular products of the sodium 
acetate systems and (b) dry sodium bicarbonate is admixed with dry, 
chemically homogeneous granules of the other components to form the first 
sodium bicarbonate system. 
Likewise, dialysis solutions (i.e., solutions for use in hemodialysis or 
peritoneal dialysis) prepared from the granular products of the first 
sodium bicarbonate system are the same as those prepared from the sodium 
acetate solutions except that sodium bicarbonate is the sole or principal 
alkalyzing agent in solutions prepared from the granular products of the 
first sodium bicarbonate system while sodium acetate is the sole or 
principal alkalyzing agent in compositions of the sodium acetate system. 
Second Sodium Bicarbonate System 
The second sodium bicarbonate system is an admixture of dry, free-flowing, 
non-caking particulate: (a) sodium chloride (b) a physiologically 
acceptable ionic salt of magnesium; (c) a physiologically acceptable ionic 
salt of calcium; (d) sodium bicarbonate; and (e) a minor amount of sodium 
acetate if required. Said magnesium and calcium salts may have ions 
selected from the group consisting of: (i) chloride; (ii) lactate; (iii) 
gluconate and (iv) acetate. Lactate, acetate and gluconate ions, if 
present, are present in minor amounts. Minor amount of potassium ions may 
also be present. 
The second sodium bicarbonate system is prepared by drying the individual 
salts which will comprise the system and mixing them after drying and 
sizing (classifying, e.g., screening). Radio frequency (microwave) heating 
is preferred for drying materials when preparing granular products of the 
second sodium bicarbonate systems but other heating methods are operable. 
If required by the patient, materials such as the potassium chloride can be 
included in the second sodium bicarbonate system. If desired, when 
including potassium, at least a portion of the potassium may be added as 
potassium bicarbonate. 
Also, if required by the patient, anhydrous dextrose may be incorporated 
into dry compositions of the first or second sodium bicarbonate systems. 
Alternatively, the dextrose can be added to the water in which such 
bicarbonate system is dissolved to form a hemodialysis solution or a 
peritoneal dialysis solution. 
Currently used dialysis procedures do not ordinarily take into account 
those materials in blood that are protein bound. Examples are iron, zinc, 
copper and cobalt. Traditionally, these materials are administered as 
separate medicants. However, it is an object of this invention to make 
such materials an integral part of dry dialysate products. Physiologically 
acceptable amounts of finely divided physiologically acceptable soluble 
salts containing materials which are normally protein bound in blood can 
be included in products of this invention. Thus, therapeutic requirements 
of such materials may be supplied during the dialysis procedure. 
The granular products of this invention are, as noted supra, useful for 
preparing hemodialysis solutions and peritoneal dialysis solutions. 
The following disclosure will make the above and other objects of this 
invention readily apparent to those skilled in the art.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
As noted supra, hemodialysis solutions are used in the process known as 
"hemodialysis", which is also referred to as "dialysis", to remove waste 
products of metabolism from the blood of a patient having renal 
deficiency. This is done by contacting the blood through a semi-permeable 
membrane with a suitable dialysis solution such that the waste products in 
the blood are removed from the blood and pass into the dialysis solution. 
It is essential that the dialysis solution contain various ions in 
specific concentration so that these will not be extracted from the 
patient's blood. 
In peritoneal dialysis (which is also known as dialysis), a dialysis 
solution is injected into a patient's abdominal cavity where waste 
products are filtered from the patient's blood, through his peritoneal 
membrane into the dialysis solution which, after taking up the waste 
products, is withdrawn from the abdominal cavity and discarded. 
Human blood contains trace quantities of many materials, but the most 
important components of concern in hemodialysis and in peritoneal dialysis 
solutions are sodium, potassium, calcium, magnesium, chlorine, hydrogen 
and hydroxyl ions and dextrose. The composition of blood varies from 
individual to individual. This necessitates using dialysis solutions 
having specific characteristics to satisfy the needs of each patient. 
Fortunately, a few formulations are effective to cover most 
patients--requiring only minor on-site use of modification to meet the 
needs of the patient. The following formulations, based on the use of 
sodium acetate as alkalyzing agent, are typical of aqueous solutions which 
are adapted for use in hemodialysis and peritoneal dialysis: 
______________________________________ 
mEq per liter.sup.(1) 
Formulation 
Na.sup.(2) 
K Ca Mg Cl Sodium Acetate 
______________________________________ 
A 134 2.5 2.5 1.5 104 36.5 
B 134 -- 2.5 1.5 101.4 36.6 
C 130 2.0 2.5 1.5 100. 36.0 
D 132 1.5 3.25 1.25 101 37.0 
E 132 1.5 3.25 1.25 101 37.0 
F 134 -- 2.5 1.5 101.4 36.6 
G 132 -- 3.25 1.25 100 36.5 
______________________________________ 
.sup.(1) Note the relative constancy of Na, Mg, Cl and acetate. K and Ca 
are main variants. In special cases, when specified by the physician, 
calcium chloride and/or magnesium chloride can be omitted. Sodium 
bicarbonate may replace sodium acetate. Dextrose may be added to these 
formulations if required. 
.sup.(2) Total sodium. 
Solutions for use in hemodialysis and/or peritoneal dialysis can be 
prepared by dissolving the granular product of this invention in sterile 
purified water. Since dextrose (glucose) is frequently a component of such 
solutions, the granular product of this invention can be mixed with 
anhydrous dextrose to prepare a dry particulate composition which will 
dissolve in said water to form a dextrose-containing solution adapted for 
use in hemodialysis and/or peritoneal dialysis. The amount of dextrose 
required can vary from patient to patient. Hence, different compositions 
containing different ratios of dextrose to said granular product can be 
prepared providing that the ratios are such that the compositions, when 
dissolved in sterile purified water, will produce solutions operable in 
hemodialysis or peritoneal dialysis. However, it should be noted that 
dextrose need not be admixed with said granular product because (a) some 
patients may not require dextrose, and (b) dextrose, if required, can be 
added while preparing a solution from the granular product of this 
invention for use in hemodialysis or peritoneal dialysis. Alternatively, 
the dextrose can be added to such solution prepared from the granules of 
this invention or to sterile purified water which will be used in 
preparing such solution. 
In one embodiment, where using sodium acetate as alkalyzing agent, the 
instant invention is directed to a process for preparing a dry granular 
product which, on solution in water, is capable of producing a 
hemodialysis or peritoneal dialysis solution. 
In another embodiment, where using sodium bicarbonate as the alkalyzing 
agent, this invention is directed to a process for preparing a dry 
granular product comprising dry granular sodium bicarbonate, which can be 
dissolved in water to produce a hemodialysis or peritoneal solution. 
Granular product of the first sodium bicarbonate system is preferably 
prepared by the rapid vaporization of water from an aqueous mixture 
wherein the water is provided: (a) in the form of water of hydration of at 
least one of the components (salts) to be granulated (i.e., incorporated 
into the product granules); (b) as liquid water in an amount sufficient to 
dissolve all of said salts present in the aqueous mixture, wherein the 
aqueous mixture is a solution; or (c) as liquid water in an amount 
insufficient to dissolve all of said salts present in the aqueous mixture 
wherein the aqueous mixture is a dispersion of small (minute) particles of 
at least one of said salts in a solution of said salts. Said small 
particles produce no feeling of graininess when rubbed between one's 
fingers and generally pass a 200-mesh U.S. standard screen. 
Under the conditions used to prepare the intimately admixed granular 
products of this invention, it is physically impossible to grow large, 
well-ordered crystals visible to the naked eye. As observed under the 
microscope, the intimately admixed granular products of this invention 
consist of an interlocked mass of small individual species (crystals or 
amorphous particles) unrecognizable to the naked eye. The particles have 
no specular characteristics (as would evidence a light-reflecting crystal 
plane of visual magnitude). When broken, the granules have a lusterless 
conchoidal fracture, which further confirms the existance of very small 
individual material domains rather than large crystals. The fact that the 
granules of this invention have a microporous structure is evidenced 
further by the rapid manner in which the unique particles of this 
invention dissolve when contacted with water. 
While any type of indirect heating can be used to remove water from an 
aqueous system to obtain a granular product of this invention, 
electromagnetic energy (e.g., ratio frequency (RF) or microwave (MW) 
energy) is particularly effective for accomplishing the rapid vaporization 
of water which is important to obtain the highest quality product. 
The use of electromagnetic energy to produce heat for vaporizing water 
while operating under reduced pressure to facilitate the removal of water 
as water vapor is particularly advantageous when preparing the 
compositions of this invention. 
It has been found that solubility properties, especially rate of solution, 
of two or more ionic salts comprising a solid mixture is greatly 
influenced by the nature of the individual salt particles and the 
association of such particles with each other prior to the instant of 
contact with water. Simple physical mixtures of individual particles of at 
least two hydrated and/or anhydrous salts dissolve markedly more slowly to 
form a desired homogeneous solution than does a composite granular 
material of comparable particle size and the same overall chemical 
composition, wherein each granule comprises an intimate association of 
very small particles of each of the several individual components or 
materials comprising the individual granules. A composition comprising 
such an intimate association or admixture of several very small indivdual 
particles of components can be prepared by first homogeneously mixing 
hydrated, or partially hydrated, salts or melts or solutions thereof, and 
subsequently removing the water rapidly to cause simultaneous deposition 
en masse of mixed small particles, each small particle being: (a) 
invisible to the naked eye; and (b) anhydrous or partially hydrated. 
Finely divided salts, not capable of forming hydrates may be included in 
the hydrous composition prior to the rapid removal of water. Each product 
granule which is visible to the naked eye is an intimate interlocked 
admixture of very small particles of each constituent. 
As set forth in more detail elsewhere in this specification, the 
composition of the first sodium bicarbonate system of this invention is 
prepared by preparing granules which do not contain sodium bicarbonate and 
admixing finely divided (e.g., -60 +200 mesh, U.S. standard) sodium 
bicarbonate and the dry sodium bicarbonate-free granules. 
The foregoing discovery has been found particularly useful for the 
preparation of dry concentrates comprising compositions of the sodium 
acetate system or the first sodium bicarbonate system of this invention 
which are useful in hemodialysis and peritoneal dialysis. 
The term "dry" in this specification means that there is no water present 
that is capable of participating in, or facilitating reaction between, 
constituents. As applied to the compotions of the first sodium bicarbonate 
system and the sodium acetate system of this invention, said term means a 
material lacking the quality of wetness and which, in a granular form, is 
free-flowing and non-caking. Dry products of this invention may contain 
individual constituents having trace amounts of bound water of hydration. 
In hemodialysis and peritoneal dialysis, it is very important that the 
composition of salt concentrates and their solubility characteristics be 
precisely and reliably controlled. Such control is readily obtained using 
the products of this invention, especially the compositions of the sodium 
acetate system and the first sodium bicarbonate system. 
In hemodialysis and peritoneal dialysis, it is very important that 
materials from which the dialysis solution is prepared be sterile. 
Accordingly, the granules of this invention are preferably prepared and 
packaged under sterile conditions, thereby avoiding a subsequent 
sterilization step. Sterility to the user is assured by adequate 
protective packaging. 
Although I do not wish to be bound by theory, I believe the granules of the 
sodium acetate system and the first sodium carbonate system of this 
invention may owe their rapid solubility properties, at least in part, to 
the fact that various salt hydrates do not lose their water of hydration 
at the same rate in a given environment. Because of this fact, when a 
complex mixture comprising a solution of an intimate (or so-called 
"chemically homogeneous") mixture of hydrated or partially hydrated salts 
or melts or solutions thereof is dried rapidly (partially or totally), 
there is little time for any one pure crystal to grow in an orderly 
manner. Rather, in each granule, a myriad of small intermixed crystals or 
amorphous particles of the individual materials present is obtained. 
Further, the granules have a degree or porosity caused by the sequential 
departure of water from the interstatial spaces left between the several 
components comprising the granules. The rapid solubility characteristics 
of products of this invention, in large part, may be due to the 
disordered, small individual component particles and the microporous 
nature of the materials comprising the granules. Some partially hydrated 
species may be included in each granule and, by their presence, may 
increase the rate of solution when the granule is dissolved. 
Conventional crystallization procedures are not applicable to the 
production of the granular products of the sodium acetate and first sodium 
carbonate systems of this invention. The art of crystallization has been 
developed extensively over the years. Much effort has been directed 
towards obtaining pure compounds from solutions of mixed materials. When a 
solution is supersaturated with respect to a specific salt, that salt 
tends to crystallize out as a pure solid phase if a suitable seed material 
is present. The formation of large, well-formed crystals of a pure 
material requires that the crystallization procedure be conducted slowly, 
allowing time for well-ordered pure crystals to grow. If one shocks the 
system, as by rapid temperature change or physical agitation, large pure 
crystals are not obtained. On the contrary, a mixture of disoriented 
smaller crystals results, tending to defeat the generally desired 
objective of conventional crystallization operations. 
This invention is directed to an improved means of preparing a 
multi-component stable, dust-free, readily soluble granular product for 
dialysis solution preparation. Because of fractionation, conventional 
crystallization processing is not an operable method for making the 
product of this invention. 
The sodium bicarbonate systems of this invention are dry, readily soluble, 
stable, free-flowing compositions which when dissolved in water produce 
relatively stable bicarbonate dialysis (hemodialysis and peritoneal 
dialysis)solutions of the type illustrated by the above-mentioned Bulletin 
of Renal Systems, Inc. 
As mentioned supra, dextrose is not required by all patients. In the 
processes and compositions of the instant invention, including all sodium 
acetate and sodium bicarbonate systems, it (dextrose) is treated as an 
optional component and handled as a separate entity. 
Dextrose may be added as an anhydrous material and be a part of the 
granular product (based on sodium acetate or on sodium bicarbonate) of 
this invention, or it may be added as a solution to dialysate solutions 
made from granular products of this invention. However, dextrose is never 
combined with the other components of the compositions of this invention 
prior to the water removing step wherein said other components are 
rendered dry. 
Further, to avoid reaction between bicarbonate and calcium and magnesium 
salts during the preparation of dialysate solutions based on sodium 
bicarbonate, the sodium bicarbonate is, as set forth above, treated as a 
separate entity and admixed with the other solid components after the 
removal of water from said solid components because, in the absence of 
water in which said solid components (and sodium bicarbonate) can 
dissolve, calcium and magnesium salts do not react with the sodium 
bicarbonate to form insoluble carbonates. 
In the preparation of the compositions of the above-mentioned first sodium 
bicarbonate system, I found that if solutions of the calcium and magnesium 
salts and sodium acetate required are first co-mingled with finely divided 
sodium chloride, followed by rapid evaporation of water as taught by 
parent application Ser. No. 123,355 filed Feb. 21, 1980 and now abandoned 
a dry solid comprising an intimate mixture of micro-particles of the 
individual salts is obtained. Further, I found that this substantially 
anhydrous composition comprising calcium and magnesium chlorides (and 
optionally, minor amounts of sodium acetate) in finely divided intimate 
admixture with micro-crystalline sodium chloride, can be admixed with 
finely divided anhydrous sodium bicarbonate and, optionally, finely 
divided anhydrous dextrose to form the first sodium bicarbonate system of 
this invention which is stable in the dry state and which dissolves 
readily in physiologically acceptable water to form a diluted solution 
suitable for dialysis use. It was also found that compositions of said 
first sodium bicarbonate system (with or without dextrose) can be 
dissolved in water (having a pH adjusted to about 6.5), using a small 
amount of acetic acid--for example, a few ml of a 5% solution of acetic 
acid per liter of water used to form stock stable solutions having 
constituent concentrations two to three times that required for dialysis 
use. 
It was also found that a less preferred composition of this invention (the 
above-described second sodium bicarbonate system) can be made by simply 
mixing finely divided substantially anhydrous calcium chloride, magnesium 
chloride and sodium chloride with finely divided dry sodium bicarbonate. 
It was found that such mixtures can be dissolved in water to form 
solutions suitable for dialysis use, but that concentrates of, for 
instance, twice or three times use concentration are relatively 
unstable--as evidenced by the early onset of precipitation of calcium and 
magnesium carbonates. 
Bicarbonate comprising dialysate solutions made from compositions of the 
aforesaid first sodium bicarbonate system of this invention are remarkably 
more stable than similar solutions prepared by adding solid sodium 
bicarbonate (or a concentrate sodium bicarbonate solution) to a solution 
comprising the other components according to the teachings of the prior 
art in that dialysis solutions prepared from compositions of said first 
sodium bicarbonate system have substantially no tendency to precipitate 
calcium carbonate and/or magnesium carbonate. 
Preferred solid granular solids of the first sodium bicarbonate systems of 
this invention having the same ratios of sodium ions, calcium ions, 
bicarbonate ions and acetate ions as the above described Solution A can 
also be used to prepare "double use strength" stock solutions having 
double the concentration of said solution A which are stable for over 72 
hours without any indication of calcium carbonate or magnesium carbonate 
precipitation when maintained at a pH of 7.2 to 7.4. After standing for 96 
hours, a small but visible amount of precipitate was observed in such 
double strength (double use concentration) stock solutions prepared from 
the first sodium bicarbonate system of this invention. Such double 
strength stock solutions can be diluted with an equal weight of water to 
prepare solutions useful as hemodialysis and as peritoneal dialysis 
solutions. 
Attempts to prepare such double strength solutions using simple dry mixture 
formulations of the second sodium bicarbonate system resulted in the 
almost instantaneous precipitation of calcium carbonate and magnesium 
carbonate. 
Such lesser stability of simple mixture formulations may be caused by 
localized high concentrations which result when solid sodium bicarbonate 
(or a concentrated sodium bicarbonate solution) is admixed with and 
dissolved in a solution containing magnesium chloride and calcium 
chloride. There is substantially no chance of obtaining such a localized 
high concentration when using the first sodium bicarbonate system of this 
invention. 
The anions and cations (excluding dextrose, which is not ionic) present in 
one liter of undiluted commercially available dialysis solution, such as 
Solution A, are: 
______________________________________ 
Na.sup.+ 3.2196 grams 
Ca.sup.++ 0.0701 grams 
Mg.sup.++ 0.0182 grams 
Cl.sup.- 3.7577 grams 
Bicarbonate Ions 2.1350 grams 
Acetate Ions 0.2362 grams 
9.4368 grams total 
______________________________________ 
As taught by the instant invention, these ions in the concentration 
required for one liter of dialysis solution can be supplied by: 
______________________________________ 
NaCl 5.9034 grams 
CH.sub.3 COONa 0.3280 grams 
CaCl.sub.2 0.1941 grams 
MgCl.sub.2 0.0713 grams 
NaHCO.sub.3 2.9400 grams 
9.4368 grams total 
______________________________________ 
The following examples illustrate embodiments whereby the product of this 
invention can be prepared. Said invention will be better understood by 
referring to said examples which are specific but non-limiting. It is 
understood that said invention is not limited by these examples, which are 
offered merely as illustrations. It is also understood that modifications 
can be made without departing from the spirit or scope of the invention. 
Examples 1-6 illustrate the preparation of compositions of the sodium 
acetate system of this invention. Examples 7-14 illustrate the preparation 
of compositions of the first sodium bicarbonate system of this invention, 
while Example 15 illustrates the preparation of a composition of the 
second sodium bicarbonate system of said invention. 
Referring to FIGS. 1, 2 and 3, it should be noted that if preparing a 
composition which does not contain potassium chloride, the feed line 
labelled "KCl" can be disconnected or the feeding of potassium chloride 
can be simply omitted. Likewise, if a composition which does not contain 
sodium acetate is being prepared, the line labelled "CH.sub.3 COONa" can 
be disconnected or the feeding of sodium acetate can be omitted. The 
H.sub.2 O line is closed (no water is fed into blender 1) in the run 
described in Example 4, but water is fed into said blender in the run 
described in Example 11. If it is desired to feed another component, such 
as sodium lactate or sodium gluconate, an additional line can be provided. 
Likewise, two additional feed lines (not shown) can be provided if two 
additional components, e.g., sodium lactate and potassium gluconate, are 
to be included in the granular product (or intermediate product) exit the 
first classifier. Water can be added when required and hydrates of 
compounds such as sodium acetate, magnesium chloride and calcium chloride, 
which forms hydrates, can be used when required or desired. The use of 
hydrates can reduce the amount of water required. 
Examples 1-6 illustrate the preparation of compositions of the sodium 
acetate system 
EXAMPLE 1 
(Thin Section Drying) 
CH.sub.3 COONa.3H.sub.2 O (174.1 g), CaCl.sub.2.2H.sub.2 O (6.5 g), 
MgCl.sub.2. 6H.sub.2 O (5.3 g), NaCl (199 g) and KCl (6.8 g) were 
intimately mixed by handworking in a mortar to produce a chemically 
homogeneous mixture which was non-gritty to the feel and felt paste-like 
(semi-fluid). The mass (391.7 grams) had a calculated water content of 
18.8%. Rapid drying in thin section (less than 7 mm thick) in a vacuum 
oven set at 120.degree. C. under static conditions produced a granular 
product weighing 318 grams. This was near the theoretical anhydrous 
weight. Said product was crushed and passed through a 20-mesh U.S. 
standard screen. The resulting product granules which passed through said 
screen were dust-free and readily and completely dissolved in water at 
30.5.degree. C. with gentle stirring in less than three minutes to form a 
30% solids by weight solution. 
A simple mixture of comparable commercial materials required more than ten 
minutes to obtain the desired 30% solution 
EXAMPLE 2 
(Thin Section Drying) 
(CH.sub.3 COO).sub.2 Mg.4H.sub.2 O (12.9 g), KCl (17.9 g), 
CaCl.sub.2.2H.sub.2 O (26.5 g), CH.sub.3 COONa.3H.sub.2 O (555.5 g) and 
NaCl (673.2 g) were ground together in a mortar at about 60.degree. C. to 
form a pasty mass. This pasty mass was tray dried in thin section (less 
than 1.6 mm thick) in an oven at 120.degree. C. The resulting dried 
product weight was 1,070 grams (which was near the theoretical dried 
weight). Said product was crushed in a mortar and passed through a 20-mesh 
screen. The product granules passing through the 20-mesh screen were 
free-flowing and dust-free. They readily and completely dissolved in water 
at 30.5.degree. C. with gentle stirring in less than three minutes to form 
a 30% (dissolved solids content) solution. 
A simple mixture of comparable commercial materials required more than ten 
minutes to obtain a similar (30%) solution 
EXAMPLE 3 
(Thin Section Drying) 
(CH.sub.3 COO).sub.2 Mg.4H.sub.2 O (12.9 g), KCl (17.9 g), CaCl.sub.2. 
2H.sub.2 O (26.5 g), CH.sub.3 COONa.3H.sub.2 O (555.5 g) and NaCl (673.2 
g) were ground together in a mortar at about 60.degree. C. to form a pasty 
mass designated "Composition 1". A 120.7 gram portion of Composition 1 was 
spread in thin section (ca. 7 mm thick) on a glass tray and placed in a 
Thermidor microwave oven made by Norris Industries of Los Angeles, Calif., 
at a "low heat" setting. Drying to constant weight was accomplished in 
approximately six minutes. It was noted that 21.5 grams of water was 
evaporated. This compares closely to the 20.7 grams of water of hydration 
associated with the sodium acetate and the other hydrates contained in the 
sample. The sample temperatures could not be measured during the heating 
process, but the glass tray was only warm to the touch on removal from the 
oven, indicating that dehydration was accomplished at a relatively low 
temperature. 
The product from this experiment was pulverized and passed through a 
20-mesh screen. The material was chemically homogeneous, dust-free and 
free-flowing. It readily and completely dissolved in less than three 
minutes in water at 30.5.degree. C. with gentle stirring to form a 30% 
solids content solution. 
In a separate run, using another portion of Composition 1 and the "high 
heat" setting of the microwave oven, rapid charring of the sodium acetate 
was observed. 
This example clearly shows that electromagnetic energy (e.g., radio 
frequency or microwave energy) can be used to rapidly remove water from 
complex salt mixtures to form dry, free-flowing, stable, dust-free 
particulate (granular) chemically homogeneous products of this invention. 
In a commercial process employing electromagnetic energy, finely divided 
recycled particles can be employed. A gas stream can be used to help 
rapidly remove water vapor from the system. Such electromagnetic energy 
dehydration process can be conducted in a thin section stationary manner, 
in a fluid bed or in an ebullient bed. Vacuum or reduced pressure may be 
employed to aid in rapid water removal. 
EXAMPLE 4 
(Fluid Bed Drying with Recycle) 
The dry, free-flowing, stable, non-caking, dust-free chemically homogeneous 
granular product of this invention can be prepared in a continuous manner 
by using the following procedure, which is designed to produce, per hour 
of plant operation, granular product sufficient for 100 unit hemodialysis 
treatments. 
Referring to FIG. 1: NaCl (56.91 kg), CH.sub.3 COONa.3H.sub.2 O (49.79 kg), 
CaCl.sub.2.2H.sub.2 O(1.86 kg), KCl (1.94 kg) and MgCl.sub.2.6H.sub.2 
O(1.5l kg) are co-mingled in blender 1 to form a fluid pasty mass at a 
rate of 112.01 kg/hr. Said fluid pasty mass (112.01 kg/hr) is passed 
(e.g., by a conveyor belt, screw conveyor or the like) proportionally and 
in a continuous manner, and at a rate of 112.01 kg/hr, to first mixer 2 
where it is intimately admixed with 90.98 kg/hr of ground or crushed 
oversize and fine recycle material from a later-recited sizing (crushing 
and classifying) operation to form a granular particulate mass which is 
passed at the rate of 202.99 kg/hr to the fluid bed dryer 3 where it is 
contacted with drying air having a flow rate and temperature effective for 
maintaining the temperature within the bed dryer 3 at 130.degree. C. Water 
is vaporized from the fluid bed at the rate of 21.03 kg/hr. Dry product 
from fluid bed dryer 3 is passed at the rate of 181.96 kg/hr to first 
crusher 4 where it is crushed. Crushed product (181.96 kg/hr) is passed 
from the first crusher 4 to the first classifier 5 from which 90.98 kg/hr 
of granular particles passing through a 20-mesh screen and retained on a 
60-mesh screen are collected as product, and the particles (90.98 kg/hr) 
retained on a 20-mesh screen or passing a 60-mesh screen are recycled. 
Particles passing the 60-mesh screen are recycled directly to first mixer 
2 while those retained on the 20-mesh screen are passed to second crusher 
6 and from there to second classifier 7. Oversize particles (particles 
retained on a 60-mesh screen) are recycled from second classifier 7 to 
second crusher 6 while those passing through said 60-mesh screen are 
passed to first mixer 2 as recycle. 
EXAMPLE 5 
(Fluid Bed Drying with Recycle) 
The dry, free-flowing, stable, non-caking, chemically homogeneous dust-free 
granular product of this invention can also be prepared in a continuous 
manner by using the following procedure, which is designed to produce 
product for 100 unit hemodialysis treatments per hour of plant operation. 
Referring to FIG. 2: NaCl (56.91 kg), CH.sub.3 COONa.3H.sub.2 O (49.79 kg), 
CaCl.sub.2.2H.sub.2 O (1.86 kg), KCl (1.94 kg), MgCl.sub.2. 6H.sub.2 O 
(1.51 kg) and water (115.44 kg) are mixed in first mixer 10 to form, at a 
rate of 227.45 kg/hr, a concentrate (solution) having a 40% dissolved 
solids content. The resulting solution is preheated under pressure to 
about 130.degree. C. (using any conventional indirect heating means, not 
shown) and introduced as a fine spray from nozzle 11 (e.g., a spray head 
nozzle such as a hollow-cone nozzle, a solid-cone nozzle, a fan nozzle, an 
impact nozzle, a rotating disc nozzle or the like), into a fluid bed dryer 
12 (where said solution is contacted with an air stream having a 
temperature and flow rate effective for maintaining a bed temperature of 
about 130.degree. C). Fluid bed dryer 12 contains a bed of previously 
prepared granules having a composition substantially the same as that 
obtained by vaporizing the water from said concentrate and having 
diameters of up to about 6.5 mm. The introduced solution is distributed 
over the surfaces of the granules within fluid bed dryer 12 which, as 
noted supra, has an internal temperature of about 130.degree. C. The 
granules in the fluid bed dryer comprise a mixture of recycled product 
from a later recited sizing (crushing and classifying) step and resident 
granular material held in the bed for contact time purposes. Water is 
evaporated from the solution added to the fluid bed dryer at the rate of 
136.47 kg/hr to yield 181.96 kg/hr of dried effluent. Said dried effluent 
is passed from fluid bed dryer 12 to first crusher 13 and from said first 
crusher to first classifier 14 at a rate of 181.96 kg/hr. Granular product 
passing a 20-mesh screen and retained on a 60-mesh screen is collected at 
the rate of 90.98 kg/hr while fines (particles passing a 60-mesh screen) 
and oversize particles (particles retained on a 20-mesh screen) totalling 
90.98 kg/hr are used as recycle. The fines are passed from first 
classifier 14 to fluid bed dryer 12, while oversize material is passed 
from first classifier 14 to second crusher 15. The oversize material, 
after being crushed in second crusher 15, passes to second classifier 16 
where it is classified. Oversize material from second classifier 16 (i.e., 
particles retained on a 60-mesh screen) are recycled to second crusher 15 
while material passing through a 60-mesh screen is recycled to fluid bed 
dryer 12. 
EXAMPLE 6 
(Spray Drying with Recycle) 
The dry, free-flowing, stable, non-caking, dust-free chemically homogeneous 
granular product of this invention can be prepared in a continuous manner 
by using the following procedure, which is designed to produce sufficient 
product for 100 hemodialysis treatments per hour of plant operation. 
Referring to FIG. 3: NaCl (56.91 kg), CH.sub.3 COONa.3H.sub.2 O (49.79 kg), 
CaCl.sub.2.2H.sub.2 O (1.86 kg), KCl (1.94 kg), MgCl.sub.2. 6H.sub.2 O 
(1.51 kg) and water (115.44 kg) are mixed in first mixer 20 to prepare a 
concentrated feed solution designated "Solution A-6" containing 40% 
dissolved solids in the amount of 227.45 kg/hour. This concentrated 
solution is pre-heated under pressure to about 150.degree. C. (using any 
conventional indirect heating means, not shown) and passed into spray 
dryer 21 in the form of small droplets from nozzle 27 (which can be a 
nozzle of the type described in Example 5, supra) where droplets are 
contacted with (a) a stream of heated drying air having a temperature and 
flow rate effective for forming the dry, granular product of this 
invention, and (b) a stream of 90.98 kg/hour of finely divided (-60 mesh) 
recycled product material from a later recited sizing (crushing and 
classifying step). 
Air exits from spray dryer 21 carrying with it 136.47 kg/hr of water and 
then passes through cyclone 22 before being vented to the atmosphere. 
Dried product (181.96 kg/hr) exits from the lower section of spray dryer 21 
in two portions, a first portion and a second portion. Said first portion 
passes directly from said spray dryer 21 to first crusher 23, while said 
second portion passes (with air exit spray dryer 21) to cyclone 22 where 
said second portion of dried product is collected and passed to first 
crusher 23. Crushed product from first crusher 23 passes to first 
classifier 24 at a rate of 181.96 kg/hr. Granular product from first 
crusher 23 passing a 20-mesh screen and retained on a 60-mesh screen is 
collected as product at the rate of 90.98 kg/hr while fines (particles 
passing a 60-mesh screen) and oversize particles (particles retained on a 
20-mesh screen) totalling 90.98 kg/hr are used as recycle. The fines are 
passed from first classifier 24 to spray dryer 21, while oversize material 
is passed from first classifier 24 to second crusher 25. The oversize 
material, after being crushed in second crusher 25, passes to second 
classifier 26 where it is classified. Oversize material from second 
classifier 26 (i.e., particles retained on a 60-mesh screen) are recycled 
to second crusher 25 while material passing through the 60-mesh screen is 
recycled to spray dryer 21. 
A granular, substantially dry product, made by simulating the process of 
this Example (Example 6) was dust-free and dissolved readily and 
completely in less than three minutes in 30.5.degree. C. water to form a 
30% solids content concentrated solution. 
Said process was simulated by placing a small amount of a solution having 
the same composition as the above-mentioned Solution A-6 along with a 
calculated amount of dry simulated recycle material having the same 
composition as the solids of Solution A-6, mixing them together with a 
spatula to form an admixture, placing the admixture on an electrically 
heated surface, and rapidly drying said admixture with a stream of warm 
air from a "hot air blower". 
Examples 7-14 illustrate the preparation of compositions of the first 
sodium bicarbonate system 
EXAMPLE 7 
(Thin Section Drying) 
The materials used in this Example were Reagent Grades of anhydrous calcium 
chloride, magnesium chloride, sodium acetate, sodium bicarbonate, and 
U.S.P. sodium chloride. All materials were dried to constant weight in a 
Thermador microwave oven made by Norris Industries of Los Angeles, Calif. 
No loss in weight was noted using the "low heat" setting. Thus, said 
starting materials used in this Example were deemed anhydrous, as 
evidenced by no weight loss when subjected to electromagnetic energy, used 
as a source of heat for obtaining dry products in this and the following 
Examples. 
CaCl.sub.2 (1.941 grams) and MgCl.sub.2 (0.713 grams) were placed in a 9" 
diameter pyrex pie plate to which was added 15 grams of water. The water 
totally dissolved the calcium and magnesium chlorides. NaCl (59.034 grams) 
was added to the solution in the dish. A gentle rubbing action with a 
spatula was sufficient to form a fluid mass indicating that the magnesium 
and calcium chloride salts were thoroughly intermixed with the dissolved 
sodium chloride and a few remaining small solid particles of sodium 
chloride. Sodium acetate (3.28 grams) was then added and the mixing action 
continued to assure thorough intermixing of said materials in the aqueous 
medium. The fluid, semi-pasty mass was then spread uniformly in the pie 
plate and subjected to electromagnetic heating to rapidly remove the water 
present. Approximately 10 grams of water was evaporated in the first two 
minutes of heating. 
After an additional two minutes of heating, it was found that the 15 grams 
of water added had been evaporated and a mixed micro-particulate product 
formed. An additional two minutes of heating produced no further weight 
loss, indicating that the product was anhydrous as defined in this 
specification. The 4.96 grams of material from the foregoing procedure was 
ground in a mortar to pass a 20-mesh screen and admixed with -60+200 
anhydrous NaHCO.sub.3 (29.4 grams), to form 94.36 grams of the 
abovementioned first sodium bicarbonate system of this invention. 
On a per liter of diluted-for-use basis, 9.4368 grams of the product of 
this Example, Example 7 (when dissolved and diluted to 1 liter) provides 
the ion concentrations commercially used as represented by Renal Systems 
SB-600. 
For laboratory check purposes (i.e., a simulated use run), to observe the 
diluted product stability of the product of this Example (Example 7) 
against the precipitation of CaCO.sub.3 and MgCO.sub.3, 1.887 grams 
(9.4368 divided by 5) of said product was added to 200 ml of deionized 
water (1000 divided by 5) having a pH of 6.5. A clear solution having a pH 
of 7.8, as measured on a precision pH meter calibrated against 
standardized buffer solutions, was obtained. The solution remained clear 
for 72 hours, indicating little tendency for CaCO.sub.3 or MgCO.sub.3 
precipitation. After about 96 hours, a small but visual amount of 
precipitate was noted, indicating precipitation of some calcium carbonate 
and/or magnesium carbonate. 
In a second simulated use run, 3.774 grams of the solid product of this 
Example (Example 7) was added with gentle mixing to 200 ml of deionized 
water, having a pH of 6.5 and containing 5% by weight of dextrose, to 
determine if a "twice use concentrate" or stock solution (a solution 
having a concentration of dissolved solids which is twice as great as that 
of a solution used in hemodialysis or peritoneal dialysis) would be stable 
against calcium and magnesium carbonate precipitation. The pH of the 
solution after mixing was 7.7. After 72 hours sending, a slight film 
formed on the bottom of the test container, indicating the possibility of 
the formation of a small amount of precipitate. However, it is apparent 
that this concentrate (a stock solution which can be diluted with water to 
form a dialysis solution, said stock solution having twice use 
concentration of a dialysis solution) is commercially feasible using the 
product of Example 7. 
In a third simulated use run, 5.661 grams of the product of this Example 
(Example 7) was added to 200 ml of deionized water of pH 6.5 to form a 
"concentrate" (a stock solution having three times the dissolved solids 
content of a dialysis solution). As in the second run, a faint film formed 
on the bottom of the test container, but the solution remained clear for 
72 hours, after which precipitation was evident. 
A fourth simulated use run used 7.548 grams of the solid product of this 
Example (Example 7) in 200 ml of deionized water having a pH of 6.5, to 
see if a "concentrate" (a stock solution having four times the dissolved 
solids content of a dialysis solution) could be prepared. A voluminous 
precipitate formed at once, indicating the precipitation of calcium 
carbonate and/or magnesium carbonate. 
The foregoing solubility/stability runs were repeated using distilled water 
having a pH of 7 and solid product from Example 7. It was found that 
solutions of said product having a dissolved solids content suitable for 
use as dialysis solutions, with and without dextrose, could be prepared. 
These solutions had a pH of near 7.8 and were stable for over 48 hours 
after which precipitates formed. Stock solutions containing twice use 
concentrations (i.e., containing twice the amount of dissolved solids 
found in dialysis solutes) had a pH of 8.2 and a heavy precipitate of 
calcium carbonate and/or magnesium carbonate was formed after 48 hours. 
These experiments indicated that the small amount of acidity in the first 
used deionized water having a pH of 6.5 was an important factor in 
lowering the pH to slow down the formation of calcium carbonate and 
magnesium carbonate precipitates. 
In hemodialysis and peritoneal dialysis practice, the diluted for use 
dialysate solution is adjusted to a pH of between 7.2 and 7.4, using a 
small amount of HCl or acetic acid if necessary, to assure compatibility 
with the blood. The pH of dialysis solutions and stock solutions, 
including those prepared from the sodium acetate system and the sodium 
bicarbonate systems of this invention can also be adjusted if necessary. 
However, it is preferred, when utilizing the sodium bicarbonate 
compositions of the first or second sodium bicarbonate systems of this 
invention, to adjust the pH of the water used to prepare dialysis 
solutions therefrom to about 6.4 prior to preparing the solutions to 
assure maintaining a pH in the range of 7.2 to 7.4 during the dilution 
process. This will mitigate against a basic environment in the solutions 
which would favor the formation and precipitation of calcium and magnesium 
carbonates. 
EXAMPLE 8 
(Thin Section Drying) 
A dry dialysate product (a first sodium bicarbonate system of this 
invention) was made comprising bicarbonate, sodium, potassium, calcium, 
magnesium, chloride and acetate which, when added to the water at the rate 
of 9.2173 grams per liter, provides the following ion constituent 
concentrations: 
______________________________________ 
Na.sup.+ 134 mEq/l 
K.sup.+ 2.5 mEq/l 
Ca.sup.++ 2.5 mEq/l 
Mg.sup.++ 1.5 mEq/l 
Cl.sup.- 101.5 mEq/l 
Bicarbonate Ions 35 mEq/l 
Acetate Ions 4 mEq/l 
______________________________________ 
The following weights of Reagent Grade anhydrous starting materials were 
used to prepare a sample sufficient to make ten liters of diluted-for-use 
dialysate solution (i.e., a solution suitable for use in hemodialysis or 
peritoneal dialysis): 
______________________________________ 
NaHCO.sub.3 29.400 grams 
MgCl.sub.2 0.712 grams 
CaCl.sub.2 1.387 grams 
KCl 1.865 grams 
Sodium Acetate 3.279 grams 
Sodium Chloride 55.530 grams 
92.173 grams total used 
______________________________________ 
CaCl.sub.2 (1.387 grams), MgCl.sub.2 (0.712 grams) and KCl (1.865 grams) 
were placed in a 9" diameter pyrex pie plate, to which was added 15 grams 
of water. The water totally dissolved the calcium, mangesium and potassium 
chlorides. NaCl (55.530 grams) was added to the solution in the dish and 
well mixed by a rubbing action with a spatula. Sodium acetate (3.279 
grams) was added and mixing of the resulting semi-fluid mass, which 
contained some finely divided undissolved sodium chloride was continued 
until all components were thoroughly admixed in the hydrous media, as in 
Example 7. Then the water was evaporated as in Example 7. 
Total water evaporation to constant weight was accomplished in less than 
four minutes in the above-described microwave oven at the "low heat" 
setting. Material (intermediate product) recovered weighed 62.77 grams, 
which was close to the theoretical value. The dried material was ground to 
pass a 20-mesh screen and 29.4 grams of finely divided (-60 +200 mesh) 
anhydrous sodium bicarbonate was admixed therewith to make the final solid 
product of this Example (Example 8), said final product being a 
composition of the first sodium bicarbonate system of this invention. 
As taught in the discussion of Example 7, supra, the product of this 
Example (Example 8) was added to distilled water adjusted to a pH of 6.5 
with acetic acid prior to use, in the amount required to prepare a 
solution suitable for use in hemodialysis or peritoneal dialysis. No 
evidence of magnesium carbonate or calcium carbonate precipitation was 
observed for over 72 hours. 
EXAMPLE 9 
(Thin Section Drying; Dextrose Added) 
The procedure of Example 7 was repated. However, in this instance, the 
procedure was modified by adding finely divided (-20 mesh) anhydrous 
dextrose to the final sodium bicarbonate-containing product of said 
Example 7 and admixing the dextrose with said product. The dextrose was 
added in an amount to provide dextrose at the rate of 250 mEq/l of 
dialysate prepared from the dextrose-containing product or composition. 
Said dextrose-containing product was excellently adapted for preparing 
dialysis solutions. 
EXAMPLE 10 
(Thin Section Drying; Dextrose Added) 
The procedure of Example 8 was repeated. However, in this instance, the 
procedure was modified by adding finely divided (-20 mesh) anhydrous 
dextrose to the final sodium bicarbonate-containing product of Example 8 
and admixing the dextrose with said product to produce a composition of 
the first sodium bicarbonate system of this invention which contains 
dextrose and potassium chloride. The dextrose was added in an amount to 
provide 250 mEq of dextrose per liter of dialysis solution. The 
dextrose-containing composition wa excellently adapted for preparing 
dialysis solutions. 
EXAMPLE 11 
(Fluid Bed Drying with Recycle) 
The dry, free-flowing, stable, non-caking dust-free granular products or 
compositions of the first sodium bicarbonate system of this invention can 
be prepared in a continuous manner by using the following procedure, which 
is designed to produce granular product. For convenience, materials used 
and produced are given on a basis of grams per ten liters of diluted 
product, i.e., on the basis of starting materials required to produce 10 
liters of dialysis (hemodialysis or peritoneal dialysis) solution, as 
described in the foregoing Example 7. 
Referring to FIG. 1: On a basis of materials required for ten liters of 
dialysis solution per hour: 1.941 grams of CaCl.sub.2, 0.712 grams 
MgCl.sub.2, 15 grams of H.sub.2 O, 59.034 grams of NaCl, 3.28 grams 
CH.sub.3 COONa and no KCl are co-mingled in blender 1 to form a fluid 
pasty mass at a rate of 79.968 grams/hour. Said fluid pasty mass (79.968 
grams/hour) is passed (e.g., by a conveyor belt, screw conveyor or the 
like) proportionally and in a continuous manner and at a rate of 79.968 
grams/hour to first mixer 2, where it is intimately admixed with 64.968 
grams/hour of ground or crushed oversize and fine recycle material from a 
later recited sizing (crushing and classifying) operation to form a 
granular particulate mass which is passed at the rate of 144.936 
grams/hour to fluid bed dryer 3, where it is contacted with drying air 
having a flow rate and temperature effective for maintaining the 
temperature of the bed within fluid bed dryer 3 at about 130.degree. C. 
Water is vaporized from the fluid bed at the rate of 15 grams/hour. Dry 
intermediate product from fluid bed dryer 3 is passed at the rate of 
129.936 grams/hour to first crusher 4 where it is crushed. Crushed 
intermediate product (129.936 grams/hour) is passed from first crusher 4 
to first classifier 5, from which 64.968 grams/hour of granular particles 
passing through a 20-mesh screen and retained on a 60-mesh screen are 
collected as intermediate product, and the particles (64.968 grams/hour) 
retained on a 20-mesh screen or passing a 60-mesh screen are recycled. 
Particles passing the 60-mesh screen are recycled directly to first mixer 
2 while those retained on the 20-mesh screen are passed to second crusher 
6 and from there to second classifier 7. Oversize particles (particles 
retained on a 60-mesh screen) are recycled from second classifier 7 to 
second crusher 6 while those passing through said 60-mesh screen are 
passed to first mixer 2 as recycle. 
The 64.968 grams/hour of intermediate product from the first classifier is 
passed to second mixer 50 (FIG. 4) where it is co-mingled with 29.4 
grams/hour of finely decided (-60 +200 mesh) anhydrous sodium bicarbonate 
to form a final product, a composition of the first sodium bicarbonate 
system of this invention. Said final product is useful for preparing 
dialysis solutions suitable for use in hemodialysis and peritoneal 
dialysis. 
EXAMPLE 12 
(Fluid Bed Drying with Recycle) 
The dry, free-flowing, stable non-caking dust-free granular products or 
compositions of the first sodium bicarbonate system of this invention can 
also be prepared in a continuous manner by using the following procedure. 
As in Example 11, materials used and products pnxked are given in 
quantities required for 10 liters per hour of a dialysate (dialysis 
solution) which is ready for use: 
Referring to FIG. 2: CaCl.sub.2 (1.941 grams), MgCl.sub.2 (0.713 grams), 
H.sub.2 O (97.452 grams), NaCl (59.034 grams), CH.sub.3 COONa (3.28 grams) 
and no KCl are mixed in a first mixer 10 to form, at a rate of 162.42 
grams/hour, a concentrate (solution) having a 40% dissolved solids 
content. The resulting solution is preheated under pressure to about 
130.degree. C. (using any conventional indirect heating means, not shown) 
and introduced as a fine spray from nozzle 11 (e.g., a spray head nozzle 
such as a hollow-cone nozzle, a solid-cone nozzle, a fan nozzle, an impact 
nozzle, a rotating disc nozzle or the like) into fluid bed dryer 12 (where 
said solution is contacted with an air stream having a temperature and 
flow rate effective for maintaining a bed temperature of about 130.degree. 
C.). Fluid bed dryer 12 contains a bed of previously prepared granules 
having a composition substantially the same as that obtained by vaporizing 
the water from said concentrate and having diameters of up to about 6.5 
mm. The introduced solution is distributed over the surfaces of the 
granules within fluid bed dryer 12 which, as noted supra, has an internal 
temperature of about 130.degree. C. The granules in the fluid bed dryer 
comprise a mixture of recycled intermediate product from a later recited 
sizing (crushing and classifying) step and resident granular material held 
in the bed for contact time purposes. Water is evaporated from the 
solution added to the fluid bed dryer at the rate of 97.452 grams/hour to 
yield 129.936 grams/hour of dried effluent. Said dried effluent is passed 
from fluid bed dryer 12 to first crusher 13 and from said first crusher to 
first classifier 14 at a rate of 129.936 grams/hour. Granular intermediate 
product passing a 20-mesh screen and retained on a 60-mesh screen is 
collected at the rate of 64.968 grams/hour while fines (particles passing 
a 60-mcsh screen) and oversize particles (particles retained on a 20-mesh 
screen) totalling 64.968 grams/hour are used as recycle. The fines are 
passed from first classifier 14 to fluid bed dryer 12, while oversized 
material is passed from first classifier 14 to second crusher 15. The 
oversize material, after being crushed in second crusher 15, passes to 
second classifier 16 where it is classified. Oversize material from second 
classifier 16 (i.e., particles retained on a 60-mesh screen) are recycled 
to second crusher 15 while material passing through a 60-mesh screen is 
recycled to fluid bed dryer 12. 
The 64.968 grams/hour of intermediate product from the first classifier is 
passed to second mixer 50 (FIG. 4) where it is co-mingled with 29.4 
grams/hour of finely divided (31 60 +200 mesh) anhydrous sodium 
bicarbonate. The combined material comprises an example of a solid sodium 
bicarbonate system of this invention which is useful for preparing 
dialysis solutions suitable and useful for use in hemodialysis and 
peritoneal dialysis. 
EXAMPLE 13 
(Spray Drying with Recycle) 
The dry, free-flowing, stable, non-caking, dust-free granular products or 
compositions of the first sodium bicarbonate system of this invention can 
be prepared in a continuous manner by using the following procedure. As in 
Example 11, materials used and product produced are given in amounts 
required for 10 liters per hour of dialysate (dialysis solution) which is 
ready for use. 
Referring to FIG. 3: CaCl.sub.2 (1.941 grams/hour), MgCl.sub.2 (0.713 
grams/hour), H.sub.2 O (97.452 grams/hour), NaCl (59.034 grams/hour), 
CH.sub.3 COONa (3.280 grams/hour) and no mixer 20 to prepare a 40% (solid 
content) concentrated feed solution in the amount of 162.42 grams/hour. 
This concentrated feed solution is pre-heated under pressure to about 
150.degree. C. (using any conventional indirect heating means not shown) 
and passed into spray dryer 21 in the form of small droplets from nozzle 
27 (which can be a nozzle of the type described in Example 12, supra) 
where droplets are contacted with (a) a stream of heated drying air having 
a temperature and flow rate effective for forming a dry, granular 
intermediate product of this invention, and (b) a stream of 64.968 
grams/hour of finely divided (-60 mcsh) recycled material from a later 
recited sizing (crushing and classifying step). 
Air exists from spray dryer 21 carrying with it 97.452 grams/hour of water 
and then passes through cyclone 22 before being vented to the atmosphere. 
Dried intermediate product (129.936 grams/hour) exits from the lower 
section of spray dryer 21 in two portions--a first portion and a second 
portion. Said first portion passes directly from said spray dryer 21 to 
first crusher 23, while said second portion passes (with air exit spray 
dryer 21) to cyclone 22 where said second portion of dried intermediate 
product is collected and passed to first crusher 23. Crushed intermediate 
product from first crusher 23 passes to first classifier 24 at a rate of 
129.936 grams/hour. Granular intermediate product from first crusher 23 
passing a 20-mesh screen and retained on a 60-mesh screen is collected at 
the rate of 64.968 grams/hour while fines (particles passing a 60-mesh 
screen) and oversize particles (particles retained on a 20-mesh screen) 
totalling 64.968 grams/hour are used as recycle. Fines are passed from 
first classifier 24 to spray dryer 21, while oversize material is passed 
from first classifier 24 to second crusher 25. The oversize material, 
after being crushed in second crusher 25, passes to second classifier 26 
where it is classified. Oversize material from second classifier 26 (i.e., 
particles retained on a 60-mesh screen) are recycled to second crusher 25 
while material passing through the 60-mesh screen is recycled to spray 
dryer 21. 
The 64.968 grams/hour of dry intermediate product from the first classifier 
is passed to second mixer 50 (FIG. 4) where it is co-mingled with 29.4 
grams/hour of finely divided (-60 +200 mesh) anhydrous sodium bicarbonate. 
The combined material comprises an example of a product of this 
invention--a first sodium bicarbonate syste useful for preparing dialysis 
solutions suitable for use in hemodialysis and peritoneal dialysis. 
When starting a run using the general procedures of Example 11, 12 or 13, 
finely divided (e.g., ca. -60 mesh) intermediate product from a previous 
run, if available, can be substituted for recycled material. If such 
intermediate product is not available, "substitute intermediate product" 
can be prepared by drying and then crushing and classifying an admixture 
of the solid starting materials or one of the solid starting 
materials--NaCl being a preferred material--but not including sodium 
bicarbonate. If desired, when using such substitute intermediate product, 
the process can be operated at substantially total recycle for about 1/2 
hour before collecting intermediate product. Alternatively, a first 
portion (e.g., the first 1/2 hour's production) of intermediate product 
obtained where using such substitute intermediate product as simulated 
recycled material can be discarded. 
When using the procedure of this Example (Example 13), fresh feed solution 
will tend to be distributed on the recycled particles in the spray dryer 
where it will tend to agglomerate said particles together during the 
drying operation to produce non-dusting intermediate product of this 
invention. Solid effluent temperature is preferably maintained between 
120.degree. and 130.degree. C. 
When using a spray dryer to prepare the granular intermediate product of 
this invention, a maximum inlet air temperature consistent with not 
over-heating the product is preferably used. The system within the spray 
dryer is cooled as water is vaporized therefrom. Thus, or energy efficient 
operation and desired product quality, an economic balance is sought and 
obtained as illustrated herein. 
EXAMPLE 14 
(Thin Section Drying; No Sodium Acetate Present) 
This example illustrates the preparation of a composition of the first 
sodium carbonate syste of the instant invention which does not contain 
sodium acetate. Following the procedure outlined in Example 7, CaCl.sub.2 
(1.941 grams) and MgCl.sub.2 (0.713 grams) were placed in a 9-inch 
diameter Pyrex pie plate to which was added 15 grams of water. The water 
totally dissolved the calcium and magnesium chlorides. NaCl (61.37 grams) 
was added to the solution in the dish. A gentle rubbing action with a 
spatula was sufficient to form a fluid mass, indicating that the magnesium 
and calcium chloride salts wer thoroughly intermixed with the dissolved 
sodium chloride and the few remaining small solid particles of sodium 
chloride. The fluid, semi-pasty mass was then spread uniformly in the pie 
plate and subjected to electromagnetic heating to rapidly remove the water 
present. Approximately 10 grams of water was evaporated in the first two 
minutes of heating. 
After an additional two minutes of heating, it was found that the 15 grams 
of water added had been evaporated, and a mixed micro-particulate product 
formed. An additional two minutes of heating produced no further weight 
loss, indicating that the product was anhydrous as defined in this 
specification. 
The 64.02 grams of material from the foregoing procedure was ground in a 
mortar to pass a 20-mesh screen and admixed with 29.4 grams of -60 +200 
mesh anhydrous sodium bicarbonate to form 93.42 grams of granular 
acetate-free product of the first sodium bicarbonate system of this 
invention. 
On a per liter of diluted for use basis, 9.342 grams of the product of this 
Example (Example 14) provides the ion concentrations commercially useful 
for dialysis (hemodialysis or peritoneal dialysis) purposes. 
I do not wish to be bound by any theory to explain the unexpected 
resistance to calcium carbonate and magnesium carbonate precipitation 
exhibited by the first sodium bicarbonate system of this invention when 
dissolved in water to prepare solutions for use in hemodialysis or for 
peritoneal dialysis. It is evident, however, that the instantly disclosed 
means of distributing the magnesium and calcium salts over the surface of 
and through the relatively large quantity of sodium chloride, all in the 
final form of mixed micro-particles having rapid solubility properties in 
admixture with finely divided and readily soluble anhydrous sodium 
bicarbonate, provides a preferred means whereby stock solutions and 
dialysates can be prepared which avoid the possibility of having an 
appreciable localized concentration of calcium, magnesium and bicarbonate 
ions which is required to cause precipitation. 
Example 15 illustrates the preparation of a composition of the second 
sodium bicarbonate system 
EXAMPLE 15 
This example demonstrates the feasibility of preparing a solid composition 
of the second sodium bicarbonate system of this invention by the simple 
admixture of finely divided anhydrous components. This is not a preferred 
procedure, but such dry products are useful for making reasonably 
stabledialysate solutions at use concentrations (i.e., having the 
concentration required for use in hemodialysis or peritoneal dialysis 
without further dilution). 
As described in Example 7 materials used in this Example were dried to 
constant weight in a microwave oven to assure the absence of any water 
that would allow reaction between the calcium and magnesium chlorides and 
sodium bicarbonate. 
Materials used in this Example are sufficient to prepare 10 liters of 
dialysis solution ready for use without further dilution. Finely divided 
(passing a 200-mesh U.S. standard screen) dry: (a) NaCl (59.034 grams), 
(b) CH.sub.3 COONa (3.28 grams), CaCl.sub.2 (1.941 grams), (d) MgCl.sub.2 
(0.713 grams), and (e) NaHCO.sub.3 (29.40 grams) were placed in a dry, 
tightly stoppered 500 ml sample bottle and well mixed by repeated shaking. 
The solid product of this Example (Example 15) is a dry composition of the 
second bicarbonate system of the instant invention, but it is a less 
preferred product than the dry composition of the first sodium bicarbonate 
system of said invention. 
As a use test of this material (the solid product of Example 15), 9.437 
grams of said material was dissolved in one liter of distilled water (the 
pH of which was first adjusted to 6.5 by the addition of dilute acetic 
acid) to form a dialysate solution suitable for use without further 
dilution. The solution having a pH of 7.2 showed no precipitate for about 
10 hours, after which a precipitate of calcium carbonate and magnesium 
carbonate was evident. A twice-use concentrate stock solution (prepared 
from said material) having such concentration that it could be diluted 
with an equal volume of water before use as a dialysis solution showed 
immediate evidence of carbonate precipitation. 
In present day commercial dialysis practice (as illustrated by instructions 
for using the above-mentioned Renal Systems SB-600), the dialysate 
solution is adjusted to a pH of between 7.2 and 7.4 after preparation, 
using a small amount of acid if necessary to assure compatibility with 
blood. Diluted solutions of the instant invention should also be adjusted 
when required. However, in using dry dialysate products comprising sodium 
bicarbonate of this invention; it is preferred to adjust the pH of the 
water used to about 6.5 prior to use, to assure maintaining a pH in the 
range of 7.2 to 7.4 during the dilution process. This preferred procedure 
mitigates against possibly forming a basic solution environment of a pH 
over approximately 7.5, which favors the formation of calcium and 
magnesium carbonates. 
The applicant cannot explain the capability of the products, as represented 
by the data given in Example 7, to form relatively stable, concentrated 
solutions. However, it is known that slight acidity, as provided by dilute 
acids or dissolved CO.sub.2 and such salts as ammonium chloride, tend to 
increase the solubility of calcium and magnesium carbonates. It may be 
that presence of other salts comprising the product of said Example 7 also 
prevent nucleation and thereby retard the onset of precipitation. 
In the development of the instant invention, the critical effect of pH, as 
it influences the onset of calcium and magnesium carbonate precipitation, 
was investigated using a sample of a composition prepared as described in 
Example 7. Solutions of twice use concentrations were used to study 
properties of the product. Table I describes materials used and 
observations made. 
The series of solubility tests shown in Table I illustrate the critical 
nature of pH insofar as being important to the onset of calcium and 
magnesium carbonate precipitation from bicarbonate comprising dialysate 
solutions. At pH values in the vicinity of 7.5 and below, the solutions 
remain stable for several days. The required accepted use range pH of 
between 7.2 and 7.4 is thus met, using products of this invention. 
TABLE I 
__________________________________________________________________________ 
ml 
Distilled 
ml 5% Grams Pro- 
pH of 
Run # 
Water CH.sub.3 COOH 
duct Used 
Solution 
Remarks 
__________________________________________________________________________ 
87-A 
200 0 3.774 7.9 "Cloudy" on mix- 
ing. Heavy pcpt. 
in 24 hours 
87-B 
200 0.5 3.774 7.8 "Clear" on mixing. 
Cloudy after 4 
hours; Pcpt after 
24 hours 
87-C 
200 1.0 3.774 7.7 "Clear" on mixing. 
Clear after 6 
hours; Small amt. 
pcpt. after 24 
hours 
87-D 
200 2.0 3.774 7.5 "Clear" on mixing. 
Clear after 6 
hours; Clear 
after 24 hours; 
Clear after 72 
hours 
87-E 
200 4.0 3.774 7.2 "Clear" on mixing. 
Clear after 6 
hours; Clear 
after 72 hours 
87-F 
200 8.0 3.774 6.7 "Clear" on mixing 
Clear after 6 
hours; Clear 
after 74 hours 
__________________________________________________________________________ 
In the course of work directed to developing an understanding of the 
importance of pH, when testing the product described in Example 15 (a 
composition of the second sodium bicarbonate system of this invention), 
there was observed what appeared to be a few small particles of 
undissolved magnesium and/or calcium chloride coated with magnesium and/or 
calcium carbonate. These were relatively large particles and not at all 
characteristic of the finely divided "cloudy" typical magnesium and 
calcium carbonate precipitates. If the pH of the particular sample was in 
the range of 7.2-7.4 and the solution was not more concentrated than use 
concentration, these particles would disappear in several hours, 
indicating that they dissolved slowly. It was also found that if a 
precipitate of calcium or magnesium carbonate formed, the addition of acid 
sufficient to lower the pH to the 7.2-7.4 range did not cause the 
precipitate to dissolve. This observation led the applicant to the 
conclusion that, with the bicarbonate systems of this invention, the pH of 
the water used should be adjusted, suitably with acetic acid, before use, 
to a value such that the final pH after mixing is in the 7.2-7.4 range. 
Conventional practice, as evidenced by Renal Systems SB-600 directions for 
use, calls for adjustment of pH after such mixing is accomplished. 
In the sodium bicarbonate systems of this invention, the term "anhydrous" 
refers to a material state such that there is no water present that can 
take part in an aqueous phase reaction between CaCl.sub.2 and NaHCO.sub.3 
or between MgCl.sub.2 and NaHCO.sub.3. In this work, it has been 
demonstrated that if a material is subjected to an R-F field (as in a 
microwave oven), water is readily vaporized and the material is rendered 
anhydrous as herein defined. 
It has also been established that water of salt hydration is readily 
removed from compositions by radio frequency (R-F) energy. Traces of water 
that may remain after R-F heating are apparently not capable of causing 
reaction between calcium or magnesium salts and sodium bicarbonate. R-F 
heating is particularly applicable to preparation of sodium acetate and 
sodium bicarbonate systems of this invention. 
It is also possible to produce substantially anhydrous NaCl, KCl, 
MgCl.sub.2 and CH.sub.3 COONa by other means of heating, such as spray 
drying and thin film surface heating above a hydrate's decomposition 
temperature, as taught in this specification, preferably using a sweep 
gas. 
Control of pH and constituent concentrations at all times and in all 
portions of any solution comprising bicarbonate ions and calcium ions 
and/or magnesium ions is necessary. At a pH of slightly above 7.4, there 
is a great tendency for magnesium and calcium carbonates to precipitate. 
Considerably supersaturation is possible but apparently not universally 
reliable as evidenced by the published literature describing the problems 
of using sodium bicarbonate as alkalizing agent in dialysate products. 
The screen size of granular product selected for use is a matter of 
convenience rather than one of necessity. For example, granular particles 
retained on a 20-mesh screen, but passing a 14 or 16 mesh screen could be 
used, except that it would take somewhat longer to dissolve them than it 
takes to dissolve granules passing a 20-mesh screen. Likewise, all 
granules passing, for example, a 14, 16, 20 or smaller (high sieve number) 
screen could be selected as product because they would dissolve quite 
rapidly, but fines (very fine particles therein) would produce some 
dusting when using the granules to prepare solutions. A body of very 
finely divided material (not in the preferred size range as herein 
described) tends to be more difficult to wet and dissolve than a granular 
material having the same chemical composition through which liquid can 
readily permeate. Thus, a minimum size, e.g., +60 mesh, +80 mesh or +100 
mesh is generally selected for product particles (intermediate product 
particles in the case of a composition of the first sodium bicarbonate 
system of this invention. However, as noted supra, the choice of both 
minimum and maximum particle size is a matter of convenience rather than 
of necessity. 
Solid particulate materials used or produced in the process of this 
invention can be conveyed by conveyor belts, screw conveyors, conveyor 
buckets, continuous flow conveyors, chain conveyors and the like. 
Blenders (mixers) which are operable in the process of this invention (see, 
for example, the procedure described in Examples 4 and 11) include, but 
are not limited to, double cone blenders, twin shell vee-type blenders, 
revolving cone mixers and tumblers provided they are equipped with 
scrapers to prevent the build-up of material on their walls. Mixers which 
are operable in the process of this invention (see, for example, the 
procedure described in Example 4) also include, but are not limited to, 
blade mixers, rotor mixers, screw conveyor mixers, kneader mixers and 
ribbon mixers. 
Crushers which are operable in the process of this invention (see, for 
example, the procedures described in Examples 4-6) include, but are not 
limited to, jaw crushers, gyratory crushers, cone crushers, pan crushers, 
roll crushers, rotary crushers, impact crushers, ball or pebble mill 
crushers and disc attrition mills. 
Classifiers which are operable in the process of this invention (see, for 
example, the procedures set forth in Examples 4-6) include but are not 
limited to screens, including vibratory screens, sieves and air 
classifiers. 
It should be noted that substantially any type of rapid drying device can 
be used to prepare the product of this invention providing the temperature 
is sufficiently low that the product is not decomposed or darkened. 
A stream of drying gas (preferably heated) can be used to rapidly remove 
water from the material being dried. Pan granulators, rotary granulators 
and drum dryers are among the devices which can be used in preparation of 
products of this invention. 
The specific operations conditions required for conducting the process used 
in preparing the granular product or granular intermediate product of this 
invention can vary widely, the principal requirement being that: (a) an 
intimate moist admixture of the constituents (ionic salts) is obtained 
before drying by co-mingling said constituents, except dextrose and sodium 
bicarbonate, (e.g., forming an aqueous solution or a dispersion of said 
constituents or by thoroughly admixing said constituents in finely divided 
form with at least one of said constituents being hydrated or partially 
hydrated or in solution, or at least a portion of at least one constituent 
being in solution, and (b) said intimate admixture is rapidly dried. 
Vacuum or reduced pressure can be used in conjunction with heat to 
facilitate rapid removal of water. Also, a stream of heated air or other 
inert gas can be of value to facilitate the fast removal of water when 
using thin section drying or other drying methods. 
Ease of water removal from any particle is greatly influenced by the 
particle size, shape and nature of the material being dried. The drying 
gas temperature, degree of saturation with water and method used to 
contact the drying gas with the particle being dried are important 
economic factors. 
In the process of this invention, fluid bed drying and spray drying are 
particularly useful when product recycle is employed. One can 
advantageously use the available surface and particle heat content of the 
recycled material to obtain rapid heat transfer to the material being 
dried. The fresh feed to the process tends to be distributed in a thin 
section on the surface of the recycled material, thus obtaining rapid heat 
transfer from both the drying gas and from the recycled solids. Fresh feed 
(e.g., from a mixer as in the processes described in the procedures of 
Examples 5 and 6) may be distributed using spray nozzles or mechanically 
driven discs, wheels or the like. 
Actual particle temperatures can only be estimated in processes that 
involve preheating of an aqueous feed under pressure to a temperature 
above the boiling point of water, followed by spray drying at atmospheric 
pressure. Particles issuing under pressure from a nozzle to atmospheric 
pressure cool rapidly because of water evaporation and almost 
instantaneously obtain a temperature near that of the ambient gas and any 
particles already in the chamber. These actions tend to cause rapid 
crystallization and favor formation of products having properties sought 
by this invention. 
Process operating energy efficiency is commerically important but is not a 
limitation of the instant invention. The processes described in Examples 
1-4, supra, require evaporation of water of salt hydration only, whereas 
the processes described in Examples 5-14 require evaporation of additional 
water used to dissolve and/or thoroughly disperse the salts involved. 
In solutions used in hemodialysis or peritoneal dialysis, the 
concentrations of the various primary electrolytes are generally 
maintained near a constant level. However, these concentrations may be 
varied to meet the specific patient needs. For instance, some patients 
require special consideration regarding sodium and potassium levels. 
Dextrose is frequently included in dialysis solutions. The dextrose 
concentration of such solutions may be varied from near zero to 
approximately 4.5%. Dextrose in solution may be handled separately in the 
dialysis procedure, or finely divided anhydrous dextrose may be admixed as 
required with products of this invention. For long package shelf-life, 
anhydrous dextrose is used in combination with the products of this 
invention. This specification is not meant to be limiting insofar as 
exactly how dextrose might be utilized with products of this invention. 
However, in the course of developing the compositions and products of this 
invention, it was observed that if even a small amount of dextrose is 
present during the drying step, this dextrose tends to undergo a browning 
reaction indicating decomposition. Thus, it is preferred to include 
dextrose as a separate entity if combined with the dry, granular products 
of this invention. 
The term "dry" as applied to the granular product of this invention means 
that said product does not feel moist when pressed between one's fingers, 
that it is free-flowing and that it is substantially non-caking when 
packaged in a sealed, dry container or when stored in a dry atmosphere 
below the fusion point of the mixture for a prolonged period (e.g., six 
months or more). 
The granular product of this invention is dust-free because tossing a 100 g 
portion of said product into the air (e.g., in a laboratory) does not 
produce a visible dust in said air. 
The product granules of this invention are non-caking and free-flowing 
because a 250 g portion of said granules, after storing in a dry tightly 
closed 250 ml jar at 150.degree. C. to 35.degree. C. for three weeks, will 
flow from said jar in the form of discrete granules and not as chunks or 
lumps or aggregates of granules, when the jar is opened and inverted. 
If, when operating processes using recycle, more than a predetermined 
amount of product size granules (e.g., -20, +60 mesh) is obtained per 
hour, such excess of product size granules can be passed, along with 
oversize granules from the first classifier to a crusher, classified and 
fine particles (e.g., -40, -60 mesh or -80 mesh) recycled to maintain a 
predetermined ratio of product to recycled material. 
When starting a run using recycle and directed to the preparation of the 
sodium acetate system of this invention or to the first sodium carbonate 
system of said invention, finely divided (e g., ca. -60 mesh) product from 
a previous run, if available, can be substituted for recycled product 
material. If such product is not available, "substitute product" can be 
prepared by drying and then crushing and classifying an admixture of the 
solid starting materials (e.g., CaCl.sub.2, MgCl.sub.2, NaCl, CH.sub.3 
COONa.3H.sub.2 O, etc.). If desired, when using such substitute product, 
the process can be operated at substantially total recycle for about 1/2 
hour before collecting product. Alternatively, a first portion (e.g., the 
first 1/2 hour's production) of product obtained where using substitute 
product as recycled material can be discarded. 
When using the procedure of Examples 6 and 13, fresh feed solution will 
tend to be distributed on the recycled particles in the spray dryer where 
it will tend to agglomerate said particles together during the drying 
operation to produce the non-dusting granules of this invention. Solid 
effluent temperature is preferably maintained between 120.degree. and 
130.degree. C. 
When using a spray dryer to prepare the granular product of this invention, 
a maximum inlet air temperature consistent with not over-heating the 
product is preferably used. The system within the spray dryer is cooled as 
water is vaporized therefrom. Thus, for energy efficient operation and 
desired product quality, an economic balance is sought and obtained as 
illustrated herein. 
In the embodiments of Examples 6 and 13, recovery approaches 100% because a 
wet scrubber, not shown can (if desired) be used to recover fines (fine 
particles) in the air exit cyclone 22. Such fines can be used to prepare 
concentrated, feed solution in mixing tank 20. 
When preparing a final product (i.e., a final composition of the first 
sodium bicarbonate system of this invention, a dry granular intermediate 
product or intermediate composition, which is described supra, is formed 
and mixed in a dry state with finely divided granular or particulate dry 
sodium bicarbonate to form the composition of said first sodium 
bicarbonate system. The dry granular intermediate product is of a size 
(e.g. -20 to +60 or -14 to +80, or -16 to +70 mesh, U.S. standard) which 
is effective for dissolving in water (after admixing with said finely 
divided granular or particulate dry sodium bicarbonate) to form a dialysis 
solution and which does not form substantial amounts of dust when handled 
in a dry state. The finely divided particulate dry sodium bicarbonate is 
of a size (e.g., -20 mesh, or -20 to +100 mesh or -30 mesh, or -60 to +200 
mesh, or finer) which is effective for admixing with or coating over the 
dry granular intermediate product to form the final composition or product 
which is a composition of the first sodium bicarbonate system of this 
invention. 
The dry, intimately mixed, chemically homogeneous granular compositions (or 
products) of the sodium acetate system of this invention are of a size 
(e.g. -20 to +60 mesh or -14 to +80 mesh) which is effective for 
dissolving in water to form dialysis solutions without forming substantial 
amounts of dust when handled in a dry state. 
Recycled material (also called finely divided recycled particles) when 
preparing: (a) a composition of sodium acetate system of the instant 
invention, or (b) a composition of the first sodium bicarbonate system of 
said invention is of a size (e.g., -40 mesh or -60 mesh or -80 mesh or 
fines), which may tend to form dust when handled in a dry state and which 
is free of larger particles (e.g., particles larger than -40 mesh). The 
recycled material has the same composition as the final product when 
preparing a composition of the sodium acetate system of this invention. 
When preparing a composition of the first sodium bicarbonate system of 
this invention, the recycled material has the same composition as the 
intermediate product. 
As used herein, "mesh" or "screen size" means U.S. standard and, unless 
otherwise defined where used, percent ("%") means parts per hundred by 
weight. As used herein, the term "R-F" means radio frequency. 
As used in this specification, the terms "major" and "minor" amounts refer 
to the relative quantities of individual materials, for example, 
hemodialysis and peritoneal dialysis solutions as used normally contain 
minor amounts of potassium, calcium and magnesium ions. Namely, less than 
5 mEq/l of solution, whereas sodium and chloride ions are present in major 
amounts of over 100 mEq/l of solution. Thus, a minor amount of potassium 
salt present in a granular composition (product) of this invention is an 
amount which will provide less than 5 mEq of potassium ion per liter of 
dialysis (hemodialysis or peritoneal dialysis) solution made from said 
granular composition. 
Likewise, a minor amount of lactate ions or gluconate ions in a granular 
composition of this invention is an amount which will provide less than 5 
mEq of such ions (lactate ions or gluconate ions) per liter of dialysis 
solution made from said granular composition. 
A minor amount of sodium acetate in a granular composition of the first 
sodium bicarbonate system (or in a particulate composition of the second 
sodium bicarbonate system) of this invention is an amount such that a 
dialysis solution made from such granular composition of said first sodium 
bicarbonate system (or from such particulate composition of said second 
sodium bicarbonate system) will contain less than 5 mEq of sodium acetate 
(or acetate ions) per liter. 
In the process as used to make granular products of this invention, two or 
more salts are dissolved or partially dissolved and the water is 
subsequently removed by evaporation. During the process, various anions 
and cations coexist in solution, for example, potassium ions, sodium ions, 
acetate ions and chloride ions. On evaporation of water to form anhydrous 
salts, there may be an exchange of anions and cations. For instance, if 
sodium acetate was used and if potassium chloride was used, on evaporation 
of water, some of the acetate may actually be present in the final product 
as potassium acetate. Such possible ion exchanges are believed to have 
little, if any, importance in conducting the processes of this invention 
or on the quality of the product obtained.