USOO6099737A United States Patent (19) 11 Patent Number: 6,099.737 Sherman et al. (45) Date of Patent: Aug. 8, 2000

54 PROCESS FOR REMOVING TOXINS FROM 4,118,314 10/1978 Yoshida ...... 210/673 BLOOD USING ZIRCONIUM METALLATE 4,261,828 4/1981 Brunner et al. . 210/287 OR TITANIUM METALLATE 4,581,141 4/1986 Ash ...... 21.0/502 COMPOSITIONS 5,536,412 7/1996 Ash ...... 210/645 75 Inventors: John D. Sherman, Inverness; David S. Primary Examiner vars Cintins Bem, Arlington Heights; Gregory J. Attorney, Agent, or Firm John G. Tolomei, Frank S. Lewis, Mt. Prospect, all of Ill. Molinaro 57 ABSTRACT 73 Assignee: UOP LLC, Des Plaines, Ill. A proceSS for removing toxins from blood is disclosed. The 21 Appl. No.: 09/281,118 process involves contacting the blood with a microporous ion eXchanger to remove toxins in the blood. Alternatively, 22 Filed: Mar. 29, 1999 the blood can be contacted with a dialysis solution which is 51 Int. Cl." B01D 15/04 then contacted with the ion exchanger. The microporous ion O -1 - O ------eXchangers are represented by the following empirical for 52 U.S. Cl...... 210/691; 210/903; 210/905; mulae: 210/908; 210/909 58 Field of Search ...... 210/691, 903, AM, Zr, Si,GeOn. (I) 210/905, 908, 909, 681 and 56) References Cited AM,Ti, Si,GeOn. (II) U.S. PATENT DOCUMENTS 3,888,250 6/1975 Hill ...... 210/694 8 Claims, No Drawings 6,099.737 1 2 PROCESS FOR REMOVING TOXINS FROM charcoal along with an ion-exchanger Such as a Zeolite or a BLOOD USING ZIRCONIUM METALLATE cation-exchange resin. OR TITANIUM METALLATE There are problems associated with the adsorbents dis COMPOSITIONS closed in the above patents. For example, charcoal does not remove any water, phosphate, Sodium or other ions. Zeolites FIELD OF THE INVENTION have the disadvantage that they can partially dissolve in the This invention relates to an extracorporeal process for dialysis Solution, allowing aluminum and/or Silicon to enter removing toxins from blood. The blood is either contacted the blood. Additionally, Zeolites can adsorb Sodium, calcium directly with a microporous ion eXchange composition and potassium ions from the blood thereby requiring that which is capable of Selectively removing the toxins from the these ions be added back into the blood. blood or the blood is first contacted with a dialysis solution Applicants have developed a process which uses which is then contacted with the microporous ion eXchange microporous ion exchangers which are essentially insoluble composition. in blood or dialysis Solutions. These microporous ion eXchangers have an empirical formula on an anhydrous basis BACKGROUND OF THE INVENTION 15 of: In mammals, e.g., humans, when the kidneys and/or liver AM, Zr, Si,GeOn. (I) fail to remove metabolic waste products from the body, most of the other organs of the body also Soon fail. Accordingly, O extensive efforts have been made to discover Safe and A.M,Ti, SiGeO, (II) effective methods for removing toxins from patients blood by extracorporeal treatment of the blood. Many methods where A is an exchangeable cation Selected from the group have been proposed for removing Small molecular toxins, consisting of potassium ion, Sodium ion, rubidium ion, protein-bound molecules or larger molecules thought to be cesium ion, calcium ion, magnesium ion, hydronium ion or mixtures thereof, M is at least one framework metal Selected responsible for the coma and illness of hepatic failure. Some 25 of these toxic compounds have been identified as urea, from the group consisting of hafnium (4+), tin (4+), niobium creatine, ammonia, phenols, mercaptains, Short chain fatty (5+), titanium (4+), cerium (4+), germanium (4+), praseody acids, aromatic amino-acids, false neural transmitters mium (4+), and terbium (4+), except that M is not titanium (Octopamine), neural inhibitors (glutamate) and bile Salts. in formula (II), “p” has a value from about 1 to about 20, “X” Among these, phenols and mercaptains, along with bilirubin has a value from zero to less than 1, “n” has a value from and bacterial endotoxins, also occur as Strong protein-bound about 0 to about 12, “y” has a value from 0 to about 12, “m' toxins and are thus more difficult to effectively remove from has a value from about 3 to about 36 and 1sn+ys 12. The the blood. Middle molecular weight toxins having a molecu germanium can Substitute for the Silicon, Zirconium/titanium lar weight of about 300 to about 10,000 can also be present or combinations thereof. and are difficult to effectively remove. 35 SUMMARY OF THE INVENTION The art shows a number of ways to treat blood containing AS Stated, this invention relates to a proceSS for removing Such toxins. The classic method is of course dialysis. Dialy toxins from blood. The proceSS comprises contacting a fluid sis is defined as the removal of Substances from a liquid by containing the toxins with a microporous ion eXchanger at diffusion acroSS a Semipermeable membrane into a Second ion exchange conditions thereby removing the toxins from liquid. Dialysis of blood outside of the body (hemodialysis) 40 the fluid, the microporous ion exchanger Selected from the is the basis of the “artificial kidney.” The artificial kidney group consisting of Zirconium metallate, titanium metallate treatment procedure generally used today is Similar to that and mixtures thereof, the metallates respectively having an developed by Kolff in the early 1940s. empirical formula on an anhydrous basis of The art contains a number of disclosures which deal with improvements on artificial kidneys or artificial livers. Thus, 45 U.S. Pat. No. 4,261,828 discloses an apparatus for the AM, Zr, Si,GeOn. (I) detoxification of blood. The apparatus comprises a housing and filled with an adsorbent Such as charcoal or a resin and optionally an enzyme carrier. In order to prevent direct AM,Ti, Si,GeOn. (II) contact between the blood and the adsorbent, the adsorbent 50 where A is an exchangeable cation Selected from the group may be coated with a coating which is permeable for the consisting of potassium ion, Sodium ion, calcium ion, mag Substances to be adsorbed yet prevent the direct contact nesium ion and mixtures thereof, M is at least one frame between the corpuscular blood components and the adsor work metal Selected from the group consisting of hafnium bents. U.S. Pat. No. 4,581,141 discloses a composition for (4+), tin (4+), niobium (5+), titanium (4+), cerium (4+), use in dialysis which contains a Surface adsorptive 55 germanium (4+), praseodymium (4+), and terbium (4+), Substance, Water, a Suspending agent, urease, a calcium except that M is not titanium in formula (II), “p” has a value loaded cation exchanger, an aliphatic carboxylic acid resin from about 1 to about 20, “X” has a value from Zero to less and a metabolizable organic acid buffer. The calcium loaded than 1, “n” has a value from about 0 to about 12, “y” has a cation exchanger can be a calcium exchanged Zeolite. value from 0 to about 12, “m' has a value from about 3 to Finally, U.S. Pat. No. 5,536,412 discloses hemofiltration and 60 about 36 and 1sn+ys 12. plasmafiltration devices in which blood flows through the This and other objects and embodiments will become interior of a hollow fiber membrane and during the flow of more clear after a detailed description of the invention. blood, a Sorbent Suspension is circulated against the exterior DETAILED DESCRIPTION OF THE surfaces of the hollow fiber membrane. Another step INVENTION involves having the plasma fraction of the blood alternately 65 exit and re-enter the interior of the membrane thereby AS Stated, applicants have developed a new proceSS for effectuating removal of toxins. The Sorbent can be activated removing various toxins from blood. One essential element 6,099.737 3 4 of the instant proceSS is a microporous ion exchanger which trichloride, titanium dioxide, tin tetrachloride, tin has a large capacity and Strong affinity, i.e., Selectivity for at isopropoxide, niobium isopropoxide, hydrous niobium least ammonia. These microporous compositions are iden oxide, hafnium isopropoxide, hafnium chloride, hafnium tified as Zirconium metallate and titanium metallate compo Oxychloride, cerium chloride, cerium oxide and cerium sitions. They are further identified by their empirical for Sulfate. mulas (on an anhydrous basis) which respectively are: The titanium metallates are prepared in an analagous manner to the Zirconium metallates. Thus, the Sources of A.M., Zr, SiGeO, (I) Silicon, germanium, M metal and alkali metal are as enu merated above. The titanium Source is also as enumerated O above, namely titanium alkoxides, titanium tetrachloride, titanium trichloride and titanium dioxide. A preferred tita A.M., Ti-SiGeOn. (II) nium Source is titanium alkoxides with Specific examples In the case of formula I, the composition has a microporous being titanium isopropoxide, titanium ethoxide and titanium framework structure composed of ZrO octahedral units and butoxide. at least one of SiO2 tetrahedral units and GeO tetrahedral 15 Generally, the hydrothermal proceSS used to prepare the units. In the case of formula II, the microporous framework Zirconium metallate or titanium metallate ion exchange Structure is composed of TiO, octahedral units and at least compositions of this invention involves forming a reaction one of SiO tetrahedral units and GeO tetrahedral units. mixture which in terms of molar ratios of the oxides is In both formulas I and II, A is an exchangeable cation expressed by the formulae: Selected from the group consisting of potassium ion, Sodium ion, rubidium ion, cesium ion, calcium ion, magnesium ion, aAO:bMO2:1-bZrO.cSiO3:dGeO.eHO (III) hydronium ion or mixtures thereof, M is at least one framework metal Selected from the group consisting of and hafnium (4+), tin (4+), niobium (5+), titanium (4+), cerium aAO:bMO:1-bTiO.cSiO.dGeO.eH.O (IV) (4+), germanium (4+), praseodymium (4+), and terbium 25 (4+), “p” has a value from about 1 to about 20, “X” has a where “a” has a value from about 0.25 to about 40, “b' has value from Zero to less than 1, “n” has a value from about a value from about 0 to about 1, “q' is the valence of M, “c” 0 to about 12, “y” has a value from 0 to about 12, “m” has has a value from about 0.5 to about 30, “d” has a value from a value from about 3 to about 36 and the sum of n+y has a about 0 to about 30 and “e' has a value of 10 to about 3000. value from about 1 to about 12. That is 1s n+y s 12. In The reaction mixture is prepared by mixing the desired equation (II) M is, of course, not titanium. The M metals Sources of Zirconium, Silicon and optionally germanium, which can be inserted into the framework in place of alkali metal and optional M metal in any order to give the Zirconium will be present as MO octahedral units and thus desired mixture. It is also necessary that the mixture have a it is a requirement that they are capable of being octahedrally basic pH and preferably a pH of at least 8. The basicity of coordinated. The germanium can be inserted into the frame 35 the mixture is controlled by adding exceSS alkali hydroxide work in place of silicon and will be present as MO and/or basic compounds of the other constituents of the tetrahedral units. Additionally, germanium can be inserted mixture. Having formed the reaction mixture it is next into the framework as a MO octahedral unit replacing Some reacted at a temperature of about 100° C. to about 250 C. of the zirconium in formula (I) or some of the titanium in for a period of about 1 to about 30 days in a sealed reaction formula (II). That is, germanium can replace Some or all of 40 vessel under autogenous pressure. After the allotted time, the the Silicon, Some of the Zirconium in formula (I), Some of the mixture is filtered to isolate the solid product which is titanium in formula (II) or both silicon and zirconium or both washed with deionized water and dried in air. Silicon and titanium. AS Stated the microporous compositions of this invention The Zirconium metallates are prepared by a hydrothermal have a framework Structure of octahedral ZrO units, at least crystallization of a reaction mixture prepared by combining 45 one of tetrahedral SiO units and tetrahedral GeO units and a reactive Source of Zirconium, Silicon and/or germanium, optionally octahedral MO units. This framework results in optionally one or more M metal, at least one alkali metal and a microporous Structure having an intracrystalline pore water. The alkali metal acts as a templating agent. Any System with uniform pore diameters, i.e., the pore sizes are Zirconium compound which can be hydrolyzed to Zirconium crystallographically regular. The diameter of the pores can oxide or Zirconium hydroxide can be used. Specific 50 vary considerably from about 3A and larger. examples of these compounds include Zirconium alkoxide, AS Synthesized, the microporous compositions of this e.g., Zirconium n-propoxide, Zirconium hydroxide, Zirco invention will contain Some of the alkali metal templating nium oxychloride, Zirconium chloride, Zirconium phosphate agent in the pores. These metals are described as exchange and Zirconium oxynitrate. The Sources of Silica include able cations, meaning that they can be exchanged for other colloidal Silica, fumed Silica and Sodium Silicate. The 55 (secondary) cations. Generally, the A exchangeable cations Sources of germanium include germanium oxide, germa can be exchanged for other alkali metal cations (K, Na", nium alkoxides and germanium tetrachloride. Alkali Sources Rb, Cs'), alkaline earth cations (Mg, Ca", Sr., Ba'"), include potassium hydroxide, Sodium hydroxide, rubidium hydronium ion or mixtures thereof. The methods used to hydroxide, cesium hydroxide, Sodium carbonate, potassium eXchange one cation for another are well known in the art carbonate, rubidium carbonate, cesium carbonate, Sodium 60 and involve contacting the microporous compositions with a halide, potassium halide, rubidium halide, cesium halide, Solution containing the desired cation (at molar excess) at Sodium ethylenediamine tetraacetic acid (EDTA), potassium eXchange conditions. Exchange conditions include a tem EDTA, rubidium EDTA, and cesium EDTA. The M metals perature of about 25 C. to about 100° C. and a time of about Sources include the M metal oxides, alkoxides, halide Salts, 20 minutes to about 2 hours. The particular cation (or acetate Salts, nitrate Salts and Sulfate Salts. Specific examples 65 mixture thereof) which is present in the final product will of the M metal sources include, but are not limited to depend on the particular use and the Specific composition titanium alkoxides, titanium tetrachloride, titanium being used. 6,099.737 S 6 It is also within the scope of the invention that these In order to more fully illustrate the invention, the follow microporous ion exchange compositions can be used in ing examples are Set forth. It is to be understood that the powder form or can be formed into various shapes by means examples are only by way of illustration and are not intended well known in the art. Examples of these various shapes as an undue limitation on the broad Scope of the invention include pills, extrudates, Spheres, pellets and irregularly shaped particles. as Set forth in the appended claims. AS Stated, these compositions have particular utility in EXAMPLE 1. adsorbing various toxins from blood. Generally, the contact ing is carried out by means and apparati well known in the A Solution was prepared by mixing 2058 g of colloidal art. Thus, one technique is hemoperfusion which involves silica (DuPont Corp. identified as Ludox(RAS-40), 2210 g packing the above described microporous ion eXchange of KOH in 7655 g H2O. After several minutes of vigorous composition into a column through which the blood is Stirring 1471 g of a Zirconium acetate Solution (22.1 wt.% flowed. One such system is described in U.S. Pat. No. ZrO) were added. This mixture was stirred for an additional 4,261,828 which is incorporated by reference. As stated in 3 minutes and the resulting gel was transferred to a stainless the 828 patent, the microporous ion eXchange composition steel reactor and hydrothermally reacted for 36 hours at 200 is preferably formed into desired shapes. Such as Spheres. 15 C. The reactor was cooled to room temperature and the Additionally, the microporous ion exchange composition mixture was vacuum filtered to isolate Solids which were particles can be coated with compounds, Such as cellulose washed with deionized water and dried in air. derivatives, which are compatible with the blood but non The Solid reaction product was analyzed and found to permeable for corpuscular blood components. In one spe contain 21.2 wt.% Si, 21.5 wt.% Zr, K20.9 wt.% K, LOI cific case, Spheres of the desired ion eXchange compositions 12.8 wt. %, which gave a formula of described above can be packed into hollow fibers thereby KZrSiO3.7H2O. This product was identified as providing a Semipermeable membrane. It should also be Sample A. pointed out that more than one type of molecular Sieve can be mixed and used in the process in order to enhance the EXAMPLE 2 efficiency of the proceSS. 25 Another way of carrying out the process is to prepare a A Solution was prepared by mixing 121.5 g of colloidal Suspension or slurry of the molecular Sieve adsorbent by silica (DuPont Corp. identified as Ludox(RAS-40), 83.7 g of means known in the art Such as described is U.S. Pat. No. NaOH in 1051 g H2O. After several minutes of vigorous 5,536,412 which is incorporated by reference. The apparatus stirring 66.9 g zirconium acetate solution (22.1 wt.% ZrO) described in the 412 patent can also be used to carry out the was added. This was stirred for an additional 3 minutes and process. The process basically involves passing a fluid the resulting gel was transferred to a Stainless Steel reactor containing toxins through the interior of a hollow fiber and and hydrothermally reacted 72 hours at 200 C. The reactor during Said passing circulating a Sorbent Suspension against was cooled to room temperature and the mixture was the exterior Surfaces of the hollow fiber membrane. At the vacuum filtered to isolate Solids which were washed with Same time, intermittent pulses of positive pressure are 35 deionized water and dried in air. applied to the sorbent solution so that the fluid alternately The Solid reaction product was analyzed and found to exits and re-enters the interior of the hollow fiber membrane contain 22.7 wt.% Si, 24.8 wt.% Zr, 12.8 wt.% Na, LOI thereby removing toxins from the fluid. 13.7 wt.%, which gives a formula K. ZrSiO3.5H2O. The instant microporous ion exchange compositions can This product was identified as sample B. also be used in a conventional dialysis process where the 40 blood is first contacted with a dialysis Solution (dialysate) to EXAMPLE 3 remove uremic substances from the blood. The dialysate is A solution (60.08 g) of colloidal silica (DuPont Corp. now regenerated and recirculated. Regeneration is carried identified as Ludox(R AS-40) was slowly added over a out by contacting the urea containing dialysate with urease period of 15 minutes to a stirring solution of 64.52 g of KOH to convert the urea to ammonium ion and carbonate ion 45 dissolved in 224 g deionized HO. This was followed by the according to the equation: addition of 45.61 g zirconium acetate (Aldrich 15-16 wt.% Zr, in dilute acetic acid). When this addition was complete, In order for this reaction to proceed to completion, ammo 4.75 g hydrous NbOs (30 wt.% LOI) was added and stirred nium ions and carbonate ions must be removed. In the 50 for an additional 5 minutes. The resulting gel was transferred instant process, the microporous ion eXchangers have a large to a stirred autoclave reactor and hydrothermally treated for capacity and Selectivity for removing ammonium ions from 1 day at 200 C. After this time, the reactor was cooled to the dialysate fluid. The urease can of course be immobilized room temperature, the mixture was vacuum filtered, the on the microporous ion exchange compositions of the Solid washed with deionized water and dried in air. present invention. Details regarding bonding of urease to 55 The Solid reaction product was analyzed and found to microporous compositions can be found in U.S. Pat. No. contain 20.3 wt.% Si, 15.6 wt.% Zr, 20.2 wt.% K, 6.60 wt. 4,581,141 which is incorporated by reference. % Nb, LOI 9.32 wt. %, which give a formula of AS has also been Stated, although the instant compositions K. Zr, NbooSiO2.32 H2O. Scanning Electron are Synthesized with a variety of eXchangeable cations Microscopy (SEM) of a portion of the sample, including (“A”), it is preferred to exchange the cation with Secondary 60 EDAX of a crystal, indicated the presence of niobium, cations which are more compatible with blood or do not Zirconium, and Silicon framework elements. This product adversely affect the blood. For this reason, preferred cations was identified as Sample C. are Sodium, calcium and magnesium. An especially pre ferred composition is one containing Sodium and calcium. EXAMPLE 4 The relative amount of Sodium and calcium can vary con 65 GeO(44.62 g) was slowly added to a stirring Solution of siderably and depends on the microporous composition and 30.50 g of KOH dissolved in 140g deionized H2O. After the the concentration of these ions in the blood. addition was complete, 45.82 g ZrOC18HO dissolved in 6,099.737 7 8 140g deionized H2O was added drop-wise. The resulting gel was transferred to a Stirred autoclave reactor and hydrother TABLE 1. mally treated for 1 days at 200 C. After this time, the reactor was cooled to room temperature and the mixture was Dialysate Test Solution Composition vacuum filtered, the Solid was washed with deionized water Element mEq/L and dried in air. Na 134 Ca 2.5 The Solid reaction product was analyzed and found to K O contain 41.0 wt.% Ge, 18.4 wt.% Zr, 12.0 wt.% K, LOI Mg 1.5 6.39 wt. %, which gave a formula of NH 65 KZrGes,Os-1.84H2O. This product was identified as Sample D. Into a 25 mL vial, there were added 100 mg of the sample to be tested, to which there were added 10 ml of the above EXAMPLE 5 test dialysis Solution. The vial was placed in an upright 15 shaker and agitated at 37 C. for about 10–18 hours. The Into a 2-liter beaker, 350.0 g of tetraethylorthosilicate mixture was then filtered and the filtrate analyzed for NH (98%) and 160.83 g of titanium tetraisopropoxide (97%) concentration by ion chromatography. Based on this were placed and Stirred with a high Speed mechanical mixer. analysis, the particular Sample's ability to ion exchange Separately, 106.30 g KOH (87%) was dissolved in 768.5g ammonium ions was determined by calculating the ammo of deionized water. This solution was then added to the nium (NH) distribution coefficient (K) by using the Stirring alkoxides and agitated for an additional two hours. following formula: The reaction mixture was then transferred to a 2-liter stirred autoclave where it was digested at a temperature of 200 C. (V)(Ac) for 132 hr. while stirring at 100 rpm. The product was 25 (W)(Sc) isolated by filtration, washed thoroughly with deionized water and dried at 100° C. where: V=volume of test dialysate (mL) Elemental analysis of the product gave an empirical Ac=concentration of cation absorbed on ion-exchanger formula of Kossi. TiOss. X-ray diffraction analysis (g/mL) showed that this product had the same topology as the W =mass of ion-exchanger evaluated (g) mineral umbite. This product was identified as Sample E. Sc =concentration of cation in post reaction Supernate (g/mL) The results of the testing are presented in EXAMPLE 6 Table 2. 35 Into a 2-liter beaker, there were mixed 380.0 g of tetra TABLE 2 ethylorthosilicate (98%) and 104.8 g of titanium tetraiso propoxide (97%). Separately, a sodium hydroxide solution Ammonium K. for several molecular sieves was prepared by dissolving 58.90 g NaOH (97%) in 854.73 Sample I.D. K g deionized water. This Solution was added to the alkoxide 40 A. 178 mixture as it was stirred vigorously with a mechanical B 79 stirrer. The reaction mixture was stirred for 2 hrs. before it D 58 was introduced into a 2-liter autoclave. The reaction mixture E 17 was reacted at 200 C. at autogenous pressure for 132 hrs. F 1O The product was isolated by filtration, washed with deion 45 Zeolite W 90 ized water, and dried at 100° C. Elemental analysis showed that this product had the The results in Table 2 show that the compositions of the present invention have a wide range of K for ammonium empirical formula Naos.SizTiO7. X-ray diffraction ion and are Suitable for removing toxins from blood. analysis showed that this product had the same topology as 50 We claim as our invention: the mineral Zorite. This product was identified as Sample F. 1. A process for removing toxins from a fluid Selected from the group consisting of blood and dialysate Solution EXAMPLE 7 comprising contacting the fluid containing the toxins with a microporous ion eXchanger at ion exchange conditions Samples A to F and zeolite W (obtained from UOP LLC) 55 thereby removing the toxins from the fluid, the microporous were tested for removal of ammonium ions using the fol ion exchanger Selected from the group consisting of Zirco lowing procedure. If the compositions were not Synthesized nium metallate, titanium metallate and mixtures thereof, the in the sodium form (zeolite W was obtained in the potassium metallates respectively having an empirical formula on an form), the compositions were converted to the predomi anhydrous basis of: nantly Sodium form by contacting the compositions with a 60 Solution containing a molar excess (at least 10 fold) of AM, Zr, Si,GeOn. (I) Sodium chloride thereby exchanging the Sodium for the potassium. The exchange conditions were those typical in and the art. A test Solution was prepared by mixing 6 mL of a AM,Ti, Si,GeOn. (II) dialysate concentrate with 194 mL of deionized water and 65 0.7 g of ammonium chloride (NHCl). The final composition where A is an exchangeable cation Selected from the group of this dialysate test solution is shown in Table 1. consisting of potassium ion, Sodium ion, calcium ion, mag 6,099.737 9 10 nesium ion and mixtures thereof, M is at least one frame 3. The process of claim 1 where the fluid is a dialysate work metal Selected from the group consisting of hafnium Solution. (4+), tin (4+), niobium (5+), titanium (4+), cerium (4+), 4. The process of claim 1 where M is tin (+4). germanium (4+), praseodymium (4+), and terbium (4+), 5. The process of claim 1 where M is titanium (4+). except that M is not titanium in formula (II), “p” has a value 5 6. The process of claim 1 where M is niobium (5+). from about 1 to about 20, “X” has a value from Zero to less 7. The process of claim 1 where n=0. than 1, “n” has a value from about 0 to about 12, “y” has a 8. The process of claim 1 where A is a mixture of calcium value from 0 to about 12, “m' has a value from about 3 to and Sodium. about 36 and 1sn+ys 12. 2. The process of claim 1 where the fluid is blood.