Patented July 29, 1952 2,605,229 UNITED STATES PATENT OFFICE

No Drawing. Application April 23, 1949, Serial No. 89,373 8 Claims. (C. 252-317) This invention relates to the preparation of hydrous calcium orthophosphate gels referred to hereinafter simply as calcium phosphate gels, and methods for stabilizing and peptizing the Sane. It also includes the products resulting therefrom. Authorities on nutrition consider calcium the nutrient most lacking in the American diet. The only constant good source of calcium from foods is milk. Unfortunately, many individuals, for a variety of reasons, don't drink any milk, or don't O The calcium phosphate products in the above consume enough of it to insure their minimum equations may be different from those shown daily requirements of calcium. The calcium in depending upon the reaction conditions. In all milk is present in the form of insoluble phosphate cases they are probably either dicalcium phos which is held in effective colloidal suspension as phate, tricalcium phosphate, hydroxy apatite, a result of the dispersing-action of various agents Ca2(PO4)2-Ca(OH)2, or mixtures of two or 'present therein. more of these, except that in reaction 5, under Nutritional studies have shown that calciurn some conditions, monocalcium phosphate may be and phosphorus in their salts such as dicalcium formed as explained in Example 6. However, phosphate or tricalcium phosphate are as effec under all conditions, the by-products are those tively utilized by the body as the calcium and 20 shown. phosphorus of milk. This gave rise to attempts The great advantage of type 1 reactions in to use the calcium phosphates in nutrition as a forming water as the only by-product is but a substitute for the calcium and phosphorus-of milk. theoretical one, since the slight Solubility of cal But the insolubility of these salts and their large cium hydroxide requires the use of a large Vol particle size proved to be a great drawback to ume of calcium hydroxide solution, giving a cal their acceptance, for when added to Water or cium phosphate gel which is very dilute and other liquid they settle out quickly and leave a requires filtration for its concentration. In order gritty taste in the mouth. ...to avoid the time consuming filtration of the In the past, colloidal solutions of calcium phos gelatinous calcium phosphate precipitate, Some phate have been prepared with the aid of electro 30 have taken advantage of the increased solubility lytes, gelatin, or casein as the dispersing Or pro of calcium hydroxide in glycerine to carry out tective agents, but these solutions are unsuitable reactions of type 1 with...concentrated solutions. for nutritional purposes because they are either This avoids the necessity for filtration, but the very dilute or contain nutritionally undesirable resulting calcium phosphate gel suffers from the Substances. - serious-disadvantage of contamination with the I have discovered that it is possible to prepare large amounts of glycerine which must be used. hydrous calcium phosphate gels in a stable con It is possible to produce concentrated gels centrated form free of nutritionally undesirable directly by the reactions of type 2, since the rea substances which Will remain dispersed in Water gents are very soluble in Water, but these gels When mixed therewith, to yield a milky SuSpen 40 contain a large amount of by-product salts the sion simulating the dispersion of calcium phos major portion and, preferably, substantially all phate in milk. . . . of which must be separated before the gels can As is well known, hydrous calcium phosphate be used in nutrition. The only practical way of gels are produced in double decomposition reac doing this is by washing with water. Dialysis tions by precipitation from aqueous solutions.con- 45 could be used but would be very impractical. taining the appropriate calcium and phosphate Calcium, phosphate gels in the concentrated ions. These reactions are of the two types shown form, including not only those formed by the reac below, type 1 being illustrated by reaction 1 which tions illustrated above but also those produced produces no by-products but water, and type 2 by other reactions, are unstable in that they sep being illustrated by reactions 2 to 6 which form 50 arate water on standing. In addition, many gels by-product salts. (Reaction 2 is included under which contain...dicalcium phosphate give rise in type 2 since an acid such as hydrochloric is nec time to crystals of dicalcium phosphate probably essary to keep the monocalcium phosphate in solution with production of a by-product salt. due to the influence of acid produced by hydroly Acidis also used in reactions 3 and 4 for the same 55 intendedsis. This, use of incourse, nutrition, ruins for the when product it is formixed its purpose.) with water the crystals quickly settle to the bottom. I have found that the tendency of calcium phosphate gels to separate water and crystallize can be prevented by incorporating therewith a 2,605,229 3 4. compound capable of removing hydrogen ions sodium phosphate in 830 c.c. of water. The flask produced by hydrolysis of the gel. Compounds was then stoppered and shaken. After standing 15 minutes the mixture was filtered by water having this property include, for instance, bases pump suction on a 250 mm. diameter. Büchner Such as calcium hydroxide and magnesium hy funnel and washed with three approximately droxide, and Salts such as calcium carbonate, equal portions of water totaling 2800 c. c. Care Sodiumamount ofbicarbonate hydrogen ionsand producedSodium citrate.by hydrolysis The Was taken not to drain off too much water be depends upon the constitution of the calcium tween washings So as to prevent cracking of the phosphate gel but is Small in any case and, there filter cake. Filtration and washing took about fore, Small amounts of the compounds mentioned O 25 minutes. With the vacuum pump still run Suffice to stabilize the gel. Calcium phosphate ning, the filter cake was pressed for about 10 gels produced under certain conditions already minutes to drain off the excess Water. The cal contain some crystals, which are probably di cium phosphate gel thus obtained weighed 445 calcium phosphate, and the addition of the grams. It had a calcium to phosphorus ratio above-mentioned compounds to Such gels will 15 of 1.8. No crystals were visible. One gram of prevent further crystallization. the gel in 5 c. c. of water had a pH of 7.3. The water-soluble citrates are unique in that Eacample 2 they peptize calcium phosphate gels. I can use any of the primary, secondary and tertiary 200 grams of the gel obtained in Example 1 water-soluble citrates including those of am 20 were mixed with 3.5 grams of finely divided pre monium and the alkali metals, for instance, So cipitated calcium carbonate. After 18 days, the dium, potassium, and lithium. The Secondary pH of this treated gel was unchanged at 7.3, While and tertiary citrates have a stronger peptizing the pH of the untreated gel of Example 1 had action than the primary citrates. The addition fallen to 5.6. No crystals were present in either of a Small amount of the former immediately 25 case. Water had separated from the untreated converts a firm calcium phosphate gel to a mobile gel but not from the treated gel. However, after liquid which sets to a thixotropic gel. The pri 42 days, Crystals appeared in the original gel but mary citrates, On the other hand, do not liquefy not in the treated gel. After one year, the treated - the gels even when added in large amounts. If gel was entirely free of crystals and separated only a limited peptizing action is desired, a small 30 Water, and its pH was still 7.3; but the untreated amount of soluble citrate may be used together gel contained an abundance of large crystals, with enough of the other non-peptizing agents its pH was down to 5.3, and it contained consid mentioned to stabilize the gel. erable separated Water. The treatment of the calcium phosphate gels The Stabilizing effect of calcium carbonate was with the citrate results in the following changes: 35 observed with the use of as little as 4.6 grams to (1) The peptized gel is more readily dispersed as much as 37 grams with the calcium phosphate in water. . gel prepared as described in Example 1, from (2) The peptized gel when dispersed in water 124 grams of calcium chloride in aging tests of settles out much more slowly. from 110 to 390 days duration. On the basis of (3) There is an improvement in the taste of the Weight of the calcium phosphate gel, this the water dispersion of the peptized gel. 40 range of added calcium carbonate amounts to Before treatment with the citrate, the calcium 0.34 to 2.82 per cent of the gel. phosphate gel is a firm gelatinous mass, even Eacample 3 though it contains over 90 per cent water. Ap parently the colloidal particles of the calcium This example shows the fine state of subdivi phosphate in the gel bind water, and powerful 45 sion of the calcium phosphate in the gel and also attractive forces hold these hydrated nuclei firm the enmeshing action which the gel seems to have ly to one another to form a solid network. The on the calcium carbonate powder to prevent its effect of the added citrate seems to be twofold. Settling out, as it otherwise very quickly does First it destroys, or weakens the forces cementing When mixed with water alone. 13.6 grams of the hydrated nuclei, and second, it reduces the 50 the year-old gel containing calcium carbonate particle size of the calcium phosphate nuclei. It obtained in Example 2 were mixed with 61.4 is likely that the first effect accounts for change c.c. of Water. The milky mixture was put through number 1 listed in the preceding paragraph while a hand homogenizer and transferred to a cylin the Second effect explains changes 2 and 3. der 1 inch in diameter. After standing for two When insoluble, powdered material. Such as 55 hours there was no settling out of the gel as evi calcium carbonate and tricalcium phosphate are denced by the absence of a clear water layer on mixed into the gels of the invention, they are top, and there was no settling out of the calcium held in effective suspension when the mixture is carbonate powder. The same result is obtained dispersed in water. When the gel is mixed with water by hand stir The invention is illustrated by the following 60 ring instead of putting it through the examples in which the reagents used in preparing homogenizer. As is well known, calcium phos the gels analyzed as follows: phate or calcium carbonate when in powder form Settle out very quickly from their water Calcium chloride-80.6% anhydrous calcium mixtures. 65 Disodiumchloride phosphate-97% anhydrous disodium Eacdmple 4 phOSphate This example shows the enmeshing and Sus Trisodium phosphate-99.5% trisodium phos pending effect of the calcium phosphate gel on phate dodecahydrate powdered tricalcium phosphate. 2.5 grams of 70 finely divided precipitated calcium carbonate Eacample 1 and 9 grams of U. S. P. tricalcium phosphate A Solution of 41 grams of calcium chloride in powder Were mixed with 200 grams of the gel 830 c. c. of water was run into a flask kept in cir prepared as described in Example 1. After 185 cular motion containing a solution of 16.2 grams days no crystallization had taken place and the of disodium phosphate and 47.5 grams of tri 75 original pH of 7.5 had changed to 7.4. A two

2,605,229 5 6 hour settling test carried out in a cylinder 1 inch phosphorus ratio is close to that of dicalcium in diameter on 14.1 grams of this aged gel mix phosphate. This is undoubtedly due to the in ture - diluted with 60.9 c. c. of water, showed 3 teraction of the monoCalcium phosphate and mm. of clear water layer on top of a 141 mm. the tricalcium phosphate according to equation: column of- the gel dispersion. This result was virtually the same as that obtained from this Ca3 (PO4)2--Ca. (H2PO4)2-4CaHPO4 gel mixture on the day it was prepared in a like Eacample 7 test, when the clear water layer on top of the dispersion measured 3.5 mm. There was no de 200 grams of the gel obtained in Example 6 posit on the bottom of the cylinder in either test, were stabilized by the addition of 4.2 grams of showing that the calcium carbonate and calcium 10 calcium carbonate, whereupon the pH of the gel phosphate powders were held in suspension by became 7.1. After 120 days, the pH was 7.0. the calcium phosphate gel. No increase in the amount or size of the crystals had taken place, and no Water had separated - - - - Eacample 5 from the gel. On the other hand, the unstabilized '4.6 grams of U.S. P. Sodiuin bicarbonate Were gel, after 60 days, had declined in pH to 5.7, con mixed with 445 grams of the gel obtained in Ex tained a large amount of enlarged crystals, and ample. 1... The mixture, had a pH of 8.0. After Water had separated from it. 46 days, the pH was 7.3, after 183 days it was Eacample 8 7.2, after one year it was still 7.2, and the gel 20 A Solution of 41 grams of calcium chloride in contained no crystals or separated water. 330 C. C. Of Water Was added to a Solution of 75.5 Eacample, 6 grams of trisodium phosphate in 830 c.c. of water. A solution of 41 grams of calcium chloride in The mixture was shaken and the precipitated 830 c.c. of water was added to a solution of 43.9 gel Was filtered and Washed as described in Ex grams of disodium phosphate in 830 c.c. of Water. 2 5 annple i. 2800. C. c. of Water were used to wash the After carefully shaking just enough to obtain precipitate. The filtration Was very slow, requir complete mixing of the solutions, the mixture ing 1/2 hours. The calcium phosphate gel ob was allowed to stand for 15 minutes, and then tained weighed 370 grams. It had a calcium to filtered, and washed with 2800 c. c. of water in phosphorus ratio of 1.97 and a pH of 10.8. It had the manner described in Example, 1. The time a bitter taste, probably due to the presence of for filtration and washing was about the same as adsorbed sodium hydroxide, the origin of which in Example 1, viz. 23 minutes. The gel thus ob will be explained below. This bitter taste of the tained weighed 263 grams. It had a calcium to gel would, of course, make it unsuitable for nu phosphorus ratio of 1.71, and a pH of 6.9. Tiny tritional purposes. However, Oll stainding, the shining crystals were visible throughout the gel. pH of the gel diminished and the hitter taste More than this minimum amount of agitation disappeared. This was evidently, due to the hy of the reaction mixture of disodium phosphate drolysis of the hydrous gel with the formation and calcium chloride leads to the increased of acid. After one day, the pH of the gel was 8.1, formation of crystalline dicalcium phosphate after 6 days it was 7.4, after 15 days it was 7.1, and the resulting product is a mixture of gel 40 after 131 days it was 6.1, and after 161 days it and a considerable amount of crystals. On the was unchanged at 6.1. No crystals appeared in other hand, if the solutions are carefully mixed the gel, but some Water had separated therefrom to avoid excessive crystal formation, 23.5 per within the first few days. In order to promptly cent of the calcium is lost in the filtrate due to convert the freshly prepared gel into a stable and the formation of what is probably monocalcium edible form, its pH was adjusted to around the phosphate, according to the equation: neutral point by the addition of an acid such as phospholic, and then it was mixed with a stabiliz 5Na2HPO4-5CaCl2-cCa3 (PO4)2-1- ing Salt Such as calcium carbonate or sodium Cah PO4--Ca. (H2PO4) 2+ ONaCl bicarbonate. s The calcium to phosphorus ratio of the precipi The filtrate obtained in this example contained tated gel is 1.71, which is close to the calcium to only a slight amount of calciunn, and 2 per cent phosphorus ratio of 1.72 for an equimolecular of the phosphorus present in the original re mixture of Ca3 (PO4)2 and Cah PO4. The calcium agents. It was highly alkaline with a pH of 11.5. to phosphorus ratio of the filtrate is 0.71, which A portion of the filtrate equivalent to 1.24 granas is close to that of 0.64 for calcium monophoS of calcium chloride used in the reaction required phate. The filtrate contains considerable acid 12.7 c. c. of hydrochloric acid (0.096 N) for re material, as is shown by the large amount of tralization with phenolphthalein as indicator. sodium hydroxide solution required to neutralize When the hydrochloric acid titration of this same it with phenolphthalein as indicator. Solution was continued with the addition of a The older literature describes a gel, prepared 60 drop of methyl orange as indicator, only 2.5 c.c. from disodium phosphate and calcium chloride more hydrochloric acid was necessary to turn having a calcium to phosphorus ratio of 1.72. the indicator from Orange to pink. This indicates This calcium phosphate was assumed to be a the presence in the filtrate of a mixture of so compound which was given the name octacalcic dium hydroxide and trisodium phosphate, a con triphosphate. However, the existence of Such a clusion derived as follows: If the 12.2 c. c. of hy compound is doubtful. Also, the literature cont drochloric acid required for the neutralization tains conficting claims regarding the nature of with phenolphthalein were due to the presence the acid material present in the filtrate, Some of only trisodium phosphate, only disodium phos claiming it is monocalcium phosphate, While phate would have been formed, according to the others state that it is monosodium phosphate. 70 equation: Continued agitation of the reaction mixture of disodium phosphate and calcium chloride leads to the disappearance of almost all of the acid On continuing the titration of this disodium calcium material from the filtrate and to the phosphate With methyl Orange as indicator, ap production of a precipitate whose calcium to 75 proximately 12.2 c. c. more hydrochloric acid 2,605,229 7 8 should have been required to neutralize, accord phthalein. As mentioned before, this filtrate is rich in calcium. ing to the equation: Mixtures containing less than 63 per cent tri Sodium phosphate and more than 37 per cent di But instead, only 2.5 c. c. more hydrochloric acid Sodium phosphate all gave gels which contained Was required. no crystals. But all these reactions produced fil The production of sodium hydroxide in the trates which became richer in calcium as the per reaction between trisodium phosphate and cal cent of trisodium phosphate decreased and the cium chloride may be explained by the equation per cent of disodium phosphate increased. On Standing, all these gels crystallized, declined in Na3PO4--CaCl2--H2O=CaHPO4--NaOH--2NaCl. pH value, and Separated water. They all could This is in accord with the well-known fact that be stabilized, as in Exampe 1, by the addition trisodium phosphate hydrolyzes in water to a of a stabilizing agent such as calcium carbonate. great extent. After 8 days the filtrate from the When the proportion of trisodium phosphate gel of this example contained a small amount of 5 used in the reaction with calcium chloride rises precipitate composed of shining, thin crystals to about 70 per cent and the disodium phosphate and an amorphous Substance. The crystals are falls correspondingly to 30 per cent, the filtrate undoubtedly dicalcium phosphate, and the amor becomes alkaline, the pH of the washed gel rises phous Substance is either tricalcium phosphate or to 8.0, and the speed of filtration of the gel is hydroxy apatite. The originally clear filtrate 20 greatly reduced to about that of the 100 per cent must have held these compounds in Supersat trisodium phosphate reaction of Example 8. urated Solution and they must have been derived Eacd/mple 9 from the same compounds present in the gel. The presence of dicalcium phosphate together A calcium phosphate gel was prepared from di 25 Sodium phosphate and ammonia, as follows: A With Sodium hydroxide in the filtrate indicates Solution of 41 grams of calcium chloride in 830 that trisodium phosphate and calcium chloride C. c. of water was added to a solution of 44 grams react, in part at least, according to the above of disodium phosphate and 33 c. c. of ammonia, equation. From a consideration of the foregoing Examples Water (sp. gr. 0.90) in 830 c. c. of water. The 30 mixing and filtration procedure was the same as 6 and 8, it will be seen that in Example 6 a sol that used in Example 1. 2800 c.c. of Water Were uble acid compound is formed which is respon used for Washing. Filtration was very slow, re sible for the crystals in the gel, whereas in Ex quiring two hours. The gel so obtained weighed ample 8 a. soluble alkaline compound is formed 367 grams. It was stabilized by the addition of which is responsible for the bitter taste of the gel. I have found that by combining the re calcium carbonate. actions of Examples 6 and 8, as in Example 1 Eacample 10 Where a mixture of disodium phosphate and tri A calcium phosphate gel was prepared from Sodium phosphate is used With the calcium chlo calcium monophosphate and ammonia as fol ride, a gel is produced which is free of both crys loWS: To 76 grams of calcium monophosphate tals and bitter taste and which may be readily monohydrate in 1000 c. c. of water were added filtered and Washed. Apparently What happens 22 c. c of hydrochloric acid (sp. gr. 1.19). The re is that there is a neutralization of the soluble Sulting cloudy solution was added to 250 c. c. monocalcium phosphate by the sodium hydroxide annonia, Water (sp. gr. 0.90) in 550 c.c. of water. to form, probably, tricalcium phosphate. The mixing and filtration procedure was the The amounts of disodium phosphate and tri Same as in Example 1. 2800 c. c. of water were Sodium phosphate used in Example 1 may be used for Washing. The filtration was very slow, stated as percentages of the total theoretical requiring 2% hours. The gel so obtained weighed amounts required in Equations 5 and 6, re 356 grams. It was stabilized by the addition of spectively, for the amount of calcium chloride Calcium carbonate. used. Equation 5 requires 43.5 grams of disodium phosphate for 41 grams of calcium chloride. Eacample 11 Equation 6 requires 75.3 grams of trisodium phos phate for 41 grams of calcium chloride. I actu This example describes the isolation and iden ally used 16.2 grams of disodium phosphate, tification of the crystals of dicalcium phosphate which is 37 per cent of the amount required by 5 5 formed on aging a calcium phosphate gel. A Equation 5, and 47.5 grams of trisodium phoS 200-gram portion of the calcium phosphate gel phate, which is 63 per cent of the amount re prepared by the procedure of Example 1 from quired by Equation 6. Stated in this manner, the 41 grams of calcium chloride and a mixture of 22 mixture of Example 11 is 50 per cent disodium grams of disodium phosphate and 37.7 grams of phosphate and 50 per cent trisodium phosphate. trisodium phosphate, and aged for 109 days, was In Example 1, the mixture of 63 per cent triso mixed with 900 c.c. of water. After standing for dium phosphate and 37 per cent disodium phos 25 minutes, the suspension was decanted leaving phate produced an almost neutral filtrate. The the crystals on the bottom. The crystals were filtrate is still a little on the acid side. For in Washed four times by decantation with 250 c.c. stance, the amount of filtrate produced from the 65 portions of Water and then again in a Bichner reaction. With 1.24 grams of calcium chloride funnel. The crystals were then air dried and required only 1.2 c. c. of sodium hydroxide (0.1-N) analyzed for calcium and phosphorus. The for neutralization with phenolphthalein. The analysis showed them to be dicalcium phosphate filtrate contained only a slight amount of calci dihydrate. When viewed with a handlens they um and a considerable amount of disodium phOS Were Seen to be diamond-shaped plates with phate. On the other hand, when 1.24 grams of jagged edges and extremely sharp points. Some calcium chloride react with disodium phosphate of them were 7 mm. long. 2.3 grams of the Crys as in Example 6 with a minimum amount of stir tals were isolated. This represents an 8 per cent ring, the filtrate requires 36 c. c. of Sodium hy yield of dicalcium phosphate dihydrate based droxide (0.1 N) for neutralization with phenol 75 on the calcium chloride used. 2,605,229 9 10 Eacample 12 95 days it was 7.1 and no crystallization had The calcium phosphate gels of this, invention taken place. The effect of the citric acid was have the property of emulsifying oils with the probably to convert some of the trisodium citrate production therewith of very stable emulsions. to disodium citrate. A lemon oil emulsion was prepared by mixing Eacample 15 12.3 grams of lemon oil with 100 grams of the calcium phosphate gel described in Example 2. Other stabilizing salts may be used with the The oil was readily taken up by the gel and a Sodium citrate in case it is desired to use only pale Straw yellow soft paste was obtained. This a Small amount of the latter. Thus, to 450 grams emulsion was intact after 6 months, and no de 10 of calcium phosphate gel, prepared as described terioration in the lemon oil had occured, as was in Example , 4 grams of sodium citrate (0.33 evident. from its unmodified rich fruity color. per gram of calcium), and 1 gram of anhydrous This emulsion could be easily dispersed in water citric acid were added, which resulted in a pep to give a homogeneous dispersion of any desired tized white thixotropic gel with a pH of 7.0. Two dilution. Similar stable emulsions were obtained 5 grams of finely divided precipitated calcium car from this gel with Orange oil, olive oil, lanolin bonate were added, and after homogenizing, the and cod liver oil. resulting White thixotropic gel had a pH of 7.3. The following examples illustrate the Stabiliz After 92 days the pH was 7.2 and no crystals were ing and peptizing actions of soluble citrates on present. The calcium carbonate was held in sus calcium phosphate gels. In each example the So 20 pension and did not settle out. Instead of cal dium citrate used was trisodium citrate dihy cium carbonate, other stabilizing agents such as drate. - sodium bicarbonate can be used together with Eacample. 3 the Sodium citrate. Eacample 16 Seven grams of sodium citrate were added to 25 454 grams of calcium phosphate gel prepared as 100 grams of calcium phosphate gel prepared described in Example . This is at the rate of from trisodium phosphate according to Example 0.58 gran of sodium citrate per gram of calcium. 8, and containing 3.2 grams of calcium, were On mixing, the firm calcium phosphate gel be treated with 8 grams of sodium citrate (2.5 grams. came a thixotropic milky liquid. It was passed per gram of calcium) and homogenized. The through a hand homogenizer, and the resulting original firm gel was, thus transformed into a liquid soon set to a firm white gel. It had a pH thixotropic white gel. After 8 days, some of this, of 8.4. The pH of the original gel was 7.3, and trixotropic gel which had become translucent that of a 1 per cent aqueous Sodium citrate solu and bluish was air dried at room temperature and tion is 8.0. After 3 days, the pH of the gel with gave a transparent residue which readily dis the sodium citrate was 7.9, after 5 days it was persed in Water at room temperature to give a 7.5, and after 100 days it was 6.9. No crystals gel, unlike the dried gel of Example 13, which were present. The gel had its original white cannot be dispersed in water. color. When the liquid form of the thixotropic When the amount of sodium citrate was in gel was heated, it quickly Solidified. This Solid 40. creased to 7 grams per gram of calcium, the gel, form Would not change to a liquid condition on was transferred in a few days to a clear mobile. shaking unless it was cooled. When this pep liquid with a bluish opalescence, viz. a colloidal tized gel was dried at room temperature after solution. Standing for 8 days, it could not be dispersed Eacample 17 in Water, but gave a suspension that settled 45 The unfavorable influence of salts such as so quickly. Another interesting property of this dium chloride on the action of sodium citrate peptized gel is that it absorbs organic liquids like on calcium phosphate gels is illustrated by the alcohol and acetone to form stable emulsions following experiment in which the sodium chlo thereWith. - ride by-product Was not removed by filtration, If this thixotropic gel is allowed to air dry at A solution of 41 grams of calcium chloride in room temperature, a hard shining white enamel 110 c.c. of water was added to a solution of 75.4 like mass resembling teeth and bone is obtained. grams of trisodium phosphate and 29.8 grams of This striking result is highly suggestive in pos Sodium citrate in 30 c.c. of water. After shaking sibly pointing to the role of the plasma citrates the mixture, a white emulsion resulted which in bringing about the colloidal dispersion of the 55 broke after two days, and a clear water layer. calcium phosphates, which may be a necessary appeared on top. This mixture contained about prerequisite for the formation of the dense con 5.9 per cent sodium chloride. On longer stand pacted calcium phosphate. Structure found in ing more water separated on top. 2.5 grams of normal bone and teeth. The thixotropy exhibited Sodium citrate per gram of calcium were used in by the gel may also be common to the calcium 6. this experiment. phosphate precipitate of the animal organism, When 7 grams of Sodium citrate per gram of where the immobilizing of the precipitated cal calcium were used, a thixotropic gel was ob cium phosphate gel may be a prelude to the for tained in about one hour and no Water sepa nation of the hard bone therefronn. rated from it on standing. This stable gel grad Eacample 14 65 ually became translucent and bluish in color. Thus, the antagonistic action of sodium chlo The initially high pH of 8.4 obtained when ride may be overcome by the use of an excess adding the sodium citrate to the calcium phos of Sodium citrate. phate gel as described above may be reduced at Once to around neutrality by adding Some acid. Eacample i8 Thus to 450 grams of calcium phosphate gel 100 grams of calcium phosphate gel prepared obtained as described in Example 1, I added 12 from disodium phosphate and ammonia, as de grams of sodium citrate (1 gram per gram of cal scribed in Example 9, and containing 3.2 grams cium) and 1 gram of anhydrous citric acid. The calcium Were mixed with 3.2 grams of sodium pH of the resulting thixotropic gel was 7.5. After is citrate. A stable thixotropic gel was obtained.