BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be illustrated by examples only with reference to the accompanying drawing in which FIGS. 1 (a) and 1 (b) to show the effects of a diet containing a guanidino group containing polymer on the levels of serum phosphate, and baking in normal rats. EXAMPLES Example 1 Preparing GUANIDINO group containing resins made from polyvinyl A aminated resin is reacted in methanol under reflux with an excess of (a) 3.5-dimethylpyrazole-1-carboxamidine nitrate (b) S-methylisothiouronium sulfate or (c) O-methylpseudourea hydrogen sulphate to convert the amino groups attached the Polymer backbone into guanidino groups. The extent of the reaction can be followed by trials for each product so that reagent (a), it may be followed by extraction with ether to determine the amount of 3,5-dimethylpyrazole formed. The resin is purified by sequential washing, methanol and water until the eluate is free of inorganic ions. Resin raw materials (A) A commercially available poly (acrylonitrile-butadiene - styrene) resin has been reduced with an excess of lithium hydride, aluminum in ether or tetrahydrofuran under reflux or by catalytic hydrogenation of PtO2 (60 psi, 20 ° C) acetic acid containing sulfuric acid. The result aminated resin is purified by successive washing with dilute hydrochloric acid aqueous and then water until the eluates are free of chloride ions and inorganic cations. The Cl-form of the resin was converted to the form of free base by treatment with 1M aqueous sodium hydroxide followed by washing with water. (B) A commercially available poly (chloromethylstyrene) resin was treated with an excess of methanol solution of ammonia saturated at 20 ° C for 48 hours, then wash with water depth until the eluate is free of ammonia. Example 2 Studies in vitro determination of phosphate binding capacity of the various GUANINIDINO group containing resins made from polyvinyl The three resins were compared. (Amberlite is a trademark). A poly (styrylmethylguanidinium) chloride resin prepared as in Example 1 (B). A poly (allylguanidinium) chloride resin prepared as in Example 1 (A). Amberlite 1R410 (Cl-) as a material control. The theoretical capacity of the polymer was determined by elemental analysis. The binding capacity of the resin was determined by ion-exchange chromatography using 32 P-labeled phosphate. The columns were prepared from 5 g of dry resin. Binding experiments were performed at pH 7.4, both in the absence of competition and the presence of chloride anions. The concentrations of chloride and phosphate were 10 and 150 mM, respectively. The results are presented in Table 1. TABLE 1 ______________________________________ Phosphate Binding Capacity (mEq g 1) In the absence In the presence Theory From chloride From chloride ______________________________________ In poly (styrylmethyl - 3.8 1.02 0.47 Guanidinium) chloride In poly (allylguanidinium) 2.3 -- 1.41 Chloride Amberlite IR410 (Cl-) 4.9 -- 0.26 ______________________________________ Although poly (allylguanidinium) chloride resin has a capacity lower binding judged by binding functions, a larger proportion is bioavailable judged by the binding of 32 P-phosphate. Chloride no rival for the phosphate-binding site of polyguanidine resins, but it does so with a low yield. Thus, even when the chloride was present in 15 molar excess, phosphate binding has been reduced by 50%. It was also shown that poly (allylguanidinium) chloride resin is selective for phosphate in the presence of 150 molar excess chloride. Amberlite IR410 (Cl-) are also bound phosphate, but unless new polyguanidine resins. Example 3 In vivo studies on the ability A GUANIDINO group containing based resin polyvinyl lowering levels of serum phosphate in rats Experimental Protocol Polyvinyl based resin used was a poly (allylguanidinium) chloride resin prepared as in Example 1, which is identified as follows PVG resin. This resin composed of a cross-linked polyethylene backbone by divinyl benzene. This frame was highly substituted 2-guanidino methyl groups. The study was conducted in two stages: A) The effectiveness of the resin binder in normal rats Six rats (strain original Wistar, male, 145-160 g) were bled by the tail (0.5 ml) and fed for 7 days with (powder) rat Chow (CRM food, SDS , Essex) mixed with powder-PVG matrix (0.5 g resin/15 g diet). The rats were given 15 grams of food daily. Thereafter, the animals were bled as above, and analyzed for serum urea, creatinine and electrolytes. B) The effectiveness of the resin binder in chronic renal failure The chronic renal failure was induced in a group of 11 men, Wistar rats (weight = 160-190 g) by making a total nephrectomy (NX) in two stages: the upper and lower pole of the left kidney been abducted, then after 9-10 days by a total nephrectomy right. The control group (n = 6) included rats in which sham operations (SO) was conducted. One week after the second operation sham operated and nephrectomised rats were bled (approximately 0.5 ml peak through tail clipping). One group (n = 3 SO; N = 6 NX) was then given for 1 week, the diet of rats powder + resin (31 g / rat / day; 0.5 g resin/15 g regime). The other group (n = 3 SO; N = 5 NX) for 7 days powder rats Chow (31 g / rat / day), followed by a further week by the rat Chow + resin. Rats were bled at the end of each stage. All serum samples were then analyzed for urea, creatinine and electrolytes. Bleeding of rats was conducted at roughly the same time of day to minimize any possibility of diurnal variations. The hemoglobin data for rats used in this study was SO group (n = 5) = 17.52 ± 1.83 g / dl NX group (n = 11) = 15.32 ± 3.02 g / dl Results An efficiency of resin binder in normal rats Rats were found to eat all PVG containing food provided on a daily basis. Weight gain during the week ranged from 7-18 g Initial serum phosphate levels were significantly higher than men (3.81 ± 0.33 (6) mmol / l mean ± SD), and declined in all cases next feeding rats containing Chow PVG (Fig. 1, which shows the plots in serum phosphate and bicarbonate levels of the individual rat). The mean percentage decrease in phosphate was 15.9% (± 5.3 SD). Such a decrease of serum bicarbonate (19.7 ± 17.2% (6)) was also evident on the PVG-feeding. Calcémie levels showed no change. The data show that the resin PVG has the ability to lower levels of phosphate. B) The effectiveness of the resin binder in chronic renal failure Sub-total nephrectomy led to the emergence of chronic renal failure (CRF), as reflected by significant increases in serum creatinine and urea levels and a decrease in hemoglobin content (Table 2). The calcium levels, although slightly higher in the NX group, have failed to reach statistical significance (P = 0.052). The levels of phosphate on the other hand showed no significant alteration following sub-total nephrectomy (Table 2). TABLE 2 ______________________________________ Comparison of various biochemical parameters in Sham-Operated (SO) and Nephrectomised (NX) Rats Parameter so NX-p ______________________________________ Creatinine (μ M) 51.0 ± 2.1 78.9 ± 7.6 <0.001> 0.05 K + (mM) 5.8 ± 0.5 6.0 ± 0.3 > 0.05 Ca (mM) 2.58 ± 0.08 2.72 ± 0.15 > 0.05 Phosphate (mM) 3.49 ± 0.18 3.37 ± 0.31 > 0.05 ______________________________________ Results: Mean ± SD for animals (n). N = 6 and 11 for SO and NX Groups, respectively. The NX group of rats fed diet PVG-appear to have somewhat improved renal function, as reflected in a significant decrease in urea treatment (p = 0.013) and a small decrease in serum creatinine (Table 3). Phosphatémie were also slightly reduced (3.37 ± 0.26 (6) of 3.18 ± 0.24, p> 0.05). Kept unchanged. TABLE 3 ______________________________________ Sham operated (N = 3) Nephrectomised (N = 4) Group after PVG-After-PVG Parameter Initial for 1 wk initial 1 week ______________________________________ Na + (mM) 142.3 ± 1.15 142.7 ± 1.16 144.2 ± 5.85 142.3 ± 2.58 K + (mM) 5.6 ± 0.35 5.87 ± 0.42 6.03 ± 0.19 * 5.98 ± 0.57 Urea 5.13 ± 0.49 5.23 ± 0.15 13.25 ± 0.99 ** 11.77 ± 0.69 + + (MM de) Cre-52.0 ± 2.00 53.67 ± 2.52 77.33 ± 6.59 ** 76.17 ± 4.07 Atinine (Μ M) Ca2 + 2.53 ± 0.095 2.62 ± 0.09 2.73 ± 0.20 2.76 ± 0.085 (MM de) PO43 3.58 ± 0.01 3.38 ± 0.04 + 3.37 ± 0.26 3.18 ± 0.24 (MM de) ______________________________________ Data: mean ± SD Statistics: * P <0.05;> 0.05 in all cases). Phosphatémie SO fell in the group (3.27 ± 0.5 (3) to 2.80 ± 0.08 (3), p> 0.05), but remained unchanged in the NX group (3.11 ± 0 .15 (5) against 3.27 ± 0.35). The 2-step surgical procedure resulted in the appearance of the CRF as evidenced by the increase of urea and creatinine and a drop in hemoglobin. However, the rats were found eating well and gaining weight (comparable increases in both groups). Levels of calcium in the NX group were slightly elevated, while levels of phosphate TABLE 4 __________________________________________________ ________________________ Sham operated (N = 3) Nephrectoinised (N = 5) Group Diet-PVG Diet Diet + PVG - PVG Diet + PVG Parameter Initial For 1 week For 1 week Initial For 1 week For 1 week __________________________________________________ ________________________ Na + (mM) 141.7 ± 0.58 142.0 ± 0 141.3 ± 0.58 142.0 ± 2.00 143.4 ± 2.07 141.2 ± 0.45 K + 6.0 ± 0.56 5.93 ± 0.67 5.4 ± 0.52 5.86 ± 0.47 6.02 ± 0.13 5.96 ± 0.54 Urea (mM) 6.57 ± 0.75 6.7 ± 0.36 5.97 ± 0.32 13.16 ± 2.04 13.76 ± 2.53 11.82 ± 1.41 Creatinine (μ M) 50.0 ± 2.00 57.7 ± 2.08 ** 56.7 ± 5.69 80.8 ± 9.09 86.2 ± 9.2 81.4 ± 6.43 Ca2 + (mM) 2.63 ± 0.03 2.68 ± 0.1 2.57 ± 0.02 2.71 ± 0.06 2.78 ± 0.08 2.67 ± 0.09 PO43 - (mM) 3.41 ± 0.21 3.27 ± 0.5 2.8 ± 0.08 3.36 ± 0.39 3.11 ± 0.15 3.27 ± 0.35 __________________________________________________ ________________________ Data: mean ± SD Statistics: * P <0.05;> 3 mol / l), the low degree of renal impairment, a low-phosphate food, rats were more active and phosphate accumulation in the bones, etc., cash or a differential response to nephrectomy. Phosphate levels decreased as a result of the introduction of food in both PVG control and nephrectomised animals. It was surprisingly shown improvement in renal function after feeding rats with diet-PVG (refer to the urea and creatinine values, tables 3 and 4). Example 4 Chemical analysis of the resin polyvinyl GUANIDINO PVG The resin polymer tested consisted of a cross-linked polyethylene backbone by divinyl benzene. This frame was highly substituted 2-guanidino methyl groups. This is the resin PVG mentioned in the previous examples. (A) An analysis of the resin Capacity -- This has been determined by (I), and elemental analysis (Ii) Binding of 32 p. At pH 8.0 (I) Elemental Analysis Équilibration of the resin with HCl (1M), and then washed with distilled water and drying to constant weight of the analysis include: ______________________________________ (A) (b) ______________________________________ C 43.12 44.60 H 7.37 7.5 N 20.20 20.10 Cl 10.60 10.15 P 0 0 ______________________________________ This corresponds to a capacity of 5.3 mEq Cl-per gram of dry resin. Équilibration of the resin with H3 PO4 (1M), and then washed with distilled water and drying to constant weight of the analysis include: ______________________________________ (A) (b) ______________________________________ C 37.6 35.9 H 7.1 6.8 N 16.5 16.1 Cl 0.2 0.7 P 9.2 9.3 (PO4) 27.6 27.6 ______________________________________ This corresponds to a capacity of 2.88 mEq phosphate per gram of dry resin. Thus, the capacity of the polymer for both anions chloride and phosphate is high and compares favorably with other Dowex resins. 32 P-phosphates Resin (400 mg) was added to a narrow column containing a fine sintered glass filter. The flow through the column was adjusted to 1 ml min-1 by a peristaltic pump. The resin is washed successively with NaOH (1M, 10 mL) H2 O (20 ml) HCl (1M, 10 ml) and H2 O (20 mL). In this state of the column was completely responsible for the anion Cl. The column was then eluted with 32 phosphate (100 mM pH 8.0) to 1.0 ml, registration, the percentage of phosphate binding to each addition. The date is shown in Table 5. TABLE 5 ______________________________________ Phosphate binding capacity of the resin (pH 8.0) Fraction # Percentage of phosphate Amount of phosphate Binds (%) linked meq g-1 ______________________________________ 1 98.4 0.246 2 95.9 0.240 3 93.7 0.234 4 85.3 0.213 5 75.0 0.188 6 55.1 0.137 7 31.5 0.079 8 14.2 0.036 9 0.0 0.00 Total 1.37 ______________________________________ Each aliquot added to the column of 1 ml of Na2 HPO4 (pH 8.0, 100 mM). Thus, at pH 8.0 the ability of phosphate has been somewhat reduced to 1.37 mEq g-1 resin. It was 50% of the value obtained when phosphoric acid was used to balance the column at pH 1.0. This difference may refers to the ionic state of phosphate at the two pH values. (B) The competition between the anions for binding sites polymer Two experimental procedures were adopted: one, competition, in the absence of phosphates added and the second, competition, in the presence of phosphate (1 mM). The competition in the absence of phosphate The competition with anions was investigated following: Chloride Bicarbonate Sulfate Taurocholate Glycocholate The column (400 mg resin) was charged with 32 P-phosphates to over 80% of its capacity and balanced with Tris.HCl (pH 8.0, 5 mM). The column was then eluted with various anions competitors in 50 ml of Tris.HCl (pH 8.0, 5 mM). The results are shown in Table 6. TABLE 6 __________________________________________________ ________________________ Moving phosphate resin By various anions at pH 8.0 Na Na NaCl NaCl Na2 SO4 NaHCO3 Taurocholate Glycocholate Fraction # (10 mM) (25 mM) (10 mM) (10 mM) (10 mM) (10 mM) __________________________________________________ ________________________ 1 8.8 14.4 32.4 11.0 1.9 2.1 2 6.5 9.3 31.3 11.6 0.7 1.0 3 5.6 7.2 22.1 14.3 1.0 1.4 Total 20.9% 30.9 85.8 36.9 3.6 4.5 __________________________________________________ ________________________ Each part consisted of 50 ml column effluents. Column buffered to pH 8.0 throughout the study. Table 6 shows that the sulfate was the only reflecting the anion effective displacement activity. This is probably because SO42-can interact with guanidino functions in a manner similar to that of phosphates. The monobasic anions Cl-and HCO3 - are much less effective by moving phosphate anions. If large volumes of liquid are then used to high concentrations, Cl - eventually oust phosphate anions. This is illustrated below in Table 7. Anioniques bile salts are extremely inefficient movement of phosphate, which means they have only very low affinity for the resin. It is likely that they were unable to penetrate the resin matrix. TABLE 7 ______________________________________ Moving phosphate from the chloride resin at pH 8.0 Percent Fraction # [NaCl] mM phosphate displaced ______________________________________ 1 5 9 2 10 10.3 3 50 23 4 100 19 5 100 10.9 6 100 6.6 Total Displacement 78.8% ______________________________________ Each part consisted of 50 ml column effluents. The competition in the presence of phosphate In this investigation, the column was eluted with Tris-HCl (pH 8.0, 5 mM) containing Na2 HPO4 (1 mM) of the specific radioactivity identical to the burden of phosphate used in the resin column. In those circumstances, if the phosphate moves phosphate, radioactivity on the column will remain unchanged. In these circumstances, the move did chloride phosphate, but only with low efficiency. This is shown in Table 8 below. So no detectable phosphates has been moved in the presence of 10 mM NaCl,; However, it began to be displaced and 50 mM largest concentrations of NaCl. Resin.sym. - HPO32 - Cl - Resin.sym. - Cl - + HPO32 - All experiments were reported repeated at least twice independent. TABLE 8 ______________________________________ Moving phosphate from the chloride resin In the presence of phosphate (1 mM) pH 8.0 Percent Fraction # [NaCl] mM phosphate eluted ______________________________________ 1 5 0 2 5 0 3 5 0 4 10 0 5 50 16% 6 100 19% ______________________________________ Each fraction eluted from the column = 50 mg. Conclusions The guanidino containing resin used in this preliminary investigation is remarkably selective for phosphate anions. Monobasique anions and bile salts only phosphate move slowly. When he studied in the presence of phosphate (1 mM), only high concentrations of NaCl (50-100 mM) cause displacement of phosphates (eg <20%>