JP2981573B2 - Phosphate ion adsorbent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a phosphate ion adsorbent and a method for producing the same.

[0002] In this specification, the phosphate ion adsorption rate refers to a value obtained by the following method.

A color reagent is prepared by dissolving 1 g of ammonium molybdate in 100 ml of 15N sulfuric acid and subsequently dissolving 4 g of ferrous sulfate. Purified water 2 in 2 ml sample
After adding and mixing 4 ml of the above coloring reagent, 15 ml
After standing for a minute, the absorbance (wavelength 660 nm) is measured. The concentration of phosphate ions in the sample is calculated using a calibration curve prepared from a Na ₂ HPO ₄ solution, and the phosphate ion adsorption rate is determined from the following equation.

Phosphate ion adsorption rate (%) = [(Ci-C
e) / Ci] × 100 In the above formula, Ci represents the initial concentration (%) of phosphate ions,
e indicates the equilibrium concentration (%) of phosphate ions.

[0005]

2. Description of the Related Art Conventionally, dry aluminum hydroxide gel has been administered as a phosphate ion adsorbent to patients with chronic renal failure accompanied by hyperphosphatemia. However, the dry aluminum hydroxide gel is known to cause aluminum encephalopathy and osteopathy as side effects when administered for a long period of time because it elutes aluminum ions into the body.

Subsequently, calcium carbonate was examined as a phosphate ion adsorbent in place of the above-mentioned dried aluminum hydroxide gel, but also in this case, hypercalcemia was caused as a side effect, and the phosphate ion adsorption power was low. It is not satisfactory since it is inferior to aluminum oxide gel.

As described above, at present, no effective phosphate ion adsorbent as a therapeutic agent for hyperphosphatemia has been obtained.

On the other hand, in recent years, phosphate ions contained in domestic wastewater and industrial wastewater have become a major environmental problem. Phosphate ions in the wastewater cause eutrophication of water in lakes, rivers, etc., and cause various environmental problems such as red tide. However, an effective adsorbent for removing phosphate ions from the wastewater has not been developed yet, and an adsorbent that efficiently adsorbs phosphate ions has been widely desired.

[0009]

Means for Solving the Problems The present inventor has conducted intensive studies in view of the above-mentioned state of the art. As a result, zirconium oxide obtained by hydrolyzing zirconium salt is excellent as a phosphate ion adsorbent. I found that. Further, the present inventors have found that a zirconium oxide obtained by hydrolyzing a zirconium salt containing at least one of an alkaline earth metal ion and an oxoacid ion is a phosphate ion adsorbent having a further excellent phosphate ion adsorption power. I found that Furthermore, the present inventor has also found that by treating the surface of the zirconium oxide with an acid and / or treating with an alkaline earth metal ion, the zirconium oxide can further improve the phosphate ion adsorption power. Was. The present invention has been completed based on these findings.

That is, the present invention is characterized in that a zirconium salt or a zirconium oxide obtained by hydrolyzing a zirconium salt containing at least one of an alkaline earth metal ion and an oxo acid ion is contained as an active ingredient. And a phosphate ion adsorbent comprising, as an active ingredient, a product obtained by treating the zirconium oxide with an acid and / or an alkaline earth metal ion.

The zirconium salt used in the present invention is not particularly limited as long as it produces a zirconium oxide by hydrolysis, and known ones can be used widely. For example, zirconium oxychloride, zirconium chloride, zirconium bromide, Examples thereof include zirconium sulfate, zirconium nitrate, and zirconium alcoholate, and one or more of these can be used.

In the present invention, the zirconium salt is hydrolyzed to obtain a zirconium oxide. The hydrolysis can be easily performed by a conventional method, and may be performed, for example, in an aqueous solution. The hydrolysis may be carried out at a relatively low temperature around room temperature or lower. However, it is more effective to carry out the reaction by heating to promote the reaction under acidic conditions. It is preferable to set the temperature to about ° C. When the hydrolysis is performed under heating, the hydrolysis may be performed while refluxing as necessary. In order to accelerate the hydrolysis reaction, it is also effective to add and use an alkali source such as ammonium hydroxide, lithium hydroxide, sodium hydroxide, potassium hydroxide or the like as appropriate.

In the present invention, by further treating the zirconium oxide obtained by hydrolysis with an acid, the zirconium oxide can further improve the phosphate ion adsorption power. The acid treatment is a solution showing acidity,
For example, the reaction may be performed with hydrochloric acid, sulfuric acid, nitric acid or the like at a pH value of about 6 or less, more preferably about 0.2 to 4.0. The treatment temperature is not particularly limited and may be room temperature, but is preferably about 80 ° C. or higher from the viewpoint of the reaction rate.

In the present invention, the phosphate ion-adsorbing power can be further improved by treating the zirconium oxide obtained by hydrolysis with alkaline earth metal ions.

The alkaline earth metal ion treatment is performed in an alkaline solution. Examples of the pH adjuster used to maintain the alkalinity include an alkali source such as sodium hydroxide, potassium hydroxide, and ammonium hydroxide. The pH value of the solution is about 7.5 or more, and more preferably 8 to 9 Degree. Examples of the alkaline earth metal ion source include calcium chloride, calcium nitrate,
Examples thereof include alkaline earth metal salts such as calcium acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium sulfate, barium chloride, barium nitrate, and barium acetate. The salt concentration in the solution is 0.2 to 4.0 mol. / L, more preferably about 0.5 to 2.0 mol / 1. The processing temperature is not particularly limited and may be room temperature, but is more preferably about 60 to 80 ° C.

Further, in the present invention, by performing the acid treatment and the alkaline earth metal ion treatment in combination, the phosphate ion adsorbing power can be further improved. In this case, the product obtained by the acid treatment may be subjected to alkaline earth metal ion treatment, or the product obtained by the alkaline earth metal ion treatment may be subjected to acid treatment.

Further, in the present invention, when a zirconium salt containing an alkaline earth metal ion and / or an oxo acid ion is used as the zirconium salt, a phosphate ion further excellent in phosphate ion adsorption power is used. Can be an adsorbent. As a method of allowing the zirconium salt to contain an alkaline earth metal ion and / or an oxo acid ion, for example, it can be carried out by adding an alkaline earth metal ion source and / or an oxo acid ion source during the hydrolysis. This is advantageous because it can be carried out in parallel with the hydrolysis. As the alkaline earth metal ion source, the same alkali metal salts as exemplified above can be used. Content ratio of the alkaline earth metal ions, 0.05 to 3.0 approximately in terms of the molar ratio to the zirconium double <br/>-ion, preferably about 0.1 to 1.0. Examples of the oxoacid ion source include oxoacids such as sulfuric acid and nitric acid, and oxoacid salts such as ammonium sulfate and ammonium nitrate. It is preferable to use oxoacid salts in terms of operation. Content ratio of oxoacid ions, 0.1 to 6.0 approximately in terms of the molar ratio to the zirconium ion, more preferably suitably about 0.5 to 3.0.

When a zirconium salt containing an alkaline earth metal ion and / or an oxo acid ion is used as the zirconium salt, the resulting zirconium oxide is subjected to an acid treatment and ( Or) a better phosphate ion adsorbent can be obtained by treating with alkaline earth metal ions.

In the present invention, a zirconium salt can be used in combination with a titanium salt. That is, the present invention
A coprecipitate or complex of zirconium oxide and titanium oxide obtained by hydrolyzing a zirconium salt and a titanium salt, or a product formed by treating the same with an acid and / or an alkaline earth metal ion as described above. It also includes things. The titanium salt is not particularly limited as long as it produces a titanium oxide by hydrolysis, and widely known ones can be used, for example, titanium chloride, titanium bromide, titanium sulfate, titanium nitrate, titanium tetrapropoxide and the like. Titanium alcoholate and the like can be exemplified, and these titanium salts may contain an alkaline earth metal ion and / or an oxo acid ion similarly to the zirconium salt.

The zirconium oxide of the present invention thus obtained is physicochemically stable, can be used under a wide range of conditions as a phosphate ion adsorbent, and can be in the form of powder, capsules, granules, and pills. , Suspensions, emulsions, powders, tablets, syrups and the like.
When the zirconium oxide of the present invention is used for pharmaceuticals, it is particularly preferably treated with an alkaline earth metal ion. For example, it can be used orally as a therapeutic agent for hyperphosphatemia.

The phosphate ion adsorbent of the present invention may be used alone or in the form of a metal compound such as aluminum oxide or zirconium oxide, a nonmetal compound such as silicon dioxide, various ion exchange resins, inorganic ion exchangers, resins, activated carbon, montmorillonite, etc. Can be used as a composite carrying the product of the present invention using a clay compound or the like as a carrier, or as a composite or coprecipitate with a titanium oxide having the same properties as zirconium oxide.

[0022]

The phosphate ion adsorbent of the present invention has a maximum phosphate ion adsorption rate of 100%, and has a remarkably excellent phosphate ion adsorption power as compared with the conventional phosphate ion adsorbent.

The phosphate ion adsorbent of the present invention is useful, for example, as a therapeutic agent for hyperphosphatemia or an adsorbent for removing phosphate ions contained in radioactive waste, industrial wastewater, domestic wastewater, and the like.

[0024]

The present invention will be further clarified with reference to the following examples.

In the examples, “ZrO1” to “ZrO1”
7 "The term Gilles obtained in each Examples 1 to 7
Means conium oxide.

[0026]

Example 1 To 400 ml of stirring water, 222 g of zirconium oxychloride octahydrate was added and dissolved. After dissolution,
The mixture was heated and refluxed at 90 ° C. for 5 hours. One hour after the start of heating and refluxing, 15N ammonium hydroxide was gradually added dropwise,
The pH of the reaction solution was adjusted to 5.85. The precipitate thus formed was filtered out, washed with water, and dried at 60 ° C. to obtain zirconium oxide (ZrO1).

10 g of the obtained ZrO1 was suspended in water, and the pH of the suspension was adjusted to 1.95 by adding 10% sulfuric acid. Then, the suspension was filtered, washed with water, dried at 60 ° C., and dried with zirconium. An acid-treated product of the oxide (hereinafter, a sulfuric acid-treated product is abbreviated as (SA)) was obtained.

0.1 g of each of the obtained ZrO1 and ZrO1 (SA) was added to 0.01 W / V% Na ₂ HPO _{4 respectively.}
The solution was added to 100 ml of an aqueous solution, stirred at 37 ° C. for 1 hour, and the phosphate ion concentration of the filtrate was measured to calculate the phosphate ion adsorption rate. The adsorption rate was 52% for ZrO1 and 52% for ZrO1.
1 (SA) was 83%.

Example 2 To 60 ml of stirring water, 222 g of zirconium oxychloride octahydrate and 80 g of ammonium sulfate were added and dissolved. After dissolution, at room temperature
N ammonium hydroxide was gradually added dropwise to adjust the final pH of the reaction solution to 9.49. The resulting precipitate was filtered out, washed with water, and dried at 80 ° C. to obtain zirconium oxide (ZrO 2).

The obtained ZrO2 is acid-treated in the same manner as in Example 1 to obtain ZrO2 (SA), and ZrO2 is treated with 1.1N nitric acid in the same manner as in ZrO2 (N
A) (hereinafter, the nitric acid-treated product is abbreviated as (NA)). The phosphate ion adsorption rate of the obtained ZrO2 (SA) and ZrO2 (NA) was determined in the same manner as in Example 1, and the result was ZrO2 (SA) and ZrO2 (NA).
O2 (SA) was 40% and ZrO2 (NA) was 44%.

[0031]

Example 3 222 g of zirconium oxychloride octahydrate, 80 g of ammonium sulfate and 17 g of magnesium sulfate heptahydrate were added to and dissolved in 600 ml of stirring water. After dissolution, 15N ammonium hydroxide was gradually added dropwise at room temperature to adjust the final pH of the reaction solution to 9. It was set to K. The resulting precipitate was filtered out, washed with water, and dried at 80 ° C. to obtain zirconium oxide (ZrO 3).

The obtained ZrO3 was treated with an acid in the same manner as in Example 2, and the phosphate ion adsorption rate was determined.
3 was 19%, ZrO3 (SA) was 54%, and ZrO3 (N
A) was 54%.

[0033]

Example 4 222 g of zirconium oxychloride octahydrate and 70 g of magnesium chloride heptahydrate were added to 600 ml of stirring water.
g was added and dissolved. After dissolution, 15N ammonium hydroxide was gradually added dropwise at room temperature to adjust the final pH of the reaction solution to 9.5. The resulting precipitate is filtered out, washed with water, dried at 80 ° C. and dried with zirconium oxide (Z
rO4) was obtained.

The obtained ZrO4 was treated with an acid in the same manner as in Example 2, and the phosphate ion adsorption rate was determined.
4 is 25%, ZrO4 (SA) is 78% and ZrO4
(NA) was 90%.

[0035]

EXAMPLE 5 222 g of zirconium oxychloride octahydrate and 273 g of ammonium sulfate were added to 400 ml of stirring water, and after dissolution, the mixture was heated and refluxed at 100 ° C. for 5 hours. One hour after the start of heating and refluxing, 15N ammonium hydroxide was gradually added dropwise to adjust the pH of the reaction solution to 2.5. The precipitate thus formed is filtered out, washed with water, and washed with water.
Drying at 0 ° C. yielded a zirconium oxide (ZrO5).

The phosphate ion adsorption rate of the obtained ZrO5 was determined in the same manner as in Example 1, and found to be 100%.

[0037]

EXAMPLE 6 To 400 ml of stirring water was added 222 g of zirconium oxychloride octahydrate, 80 g of ammonium sulfate and 170 g of magnesium sulfate heptahydrate, and after dissolution,
The mixture was heated and refluxed at 0 ° C. for 5 hours. One hour after the start of the heating and refluxing, 15N ammonium hydroxide was gradually added dropwise to adjust the pH of the reaction solution to 2.0. The precipitate thus formed was filtered out, washed with water, and dried at 60 ° C. to obtain zirconium oxide (ZrO6).

The phosphate ion adsorption rate of the obtained ZrO6 was determined in the same manner as in Example 1, and was found to be 100%.

Example 7 222 g of zirconium oxychloride octahydrate and 101 g of calcium chloride dihydrate were added to 400 ml of stirring water, and after dissolution, the mixture was heated and refluxed at 100 ° C. for 3 hours. Two hours after the start of the heating and refluxing, 15N ammonium hydroxide was gradually added dropwise to adjust the pH of the reaction solution to 2.5. The precipitate thus formed was filtered out, washed with water, and dried at 60 ° C. to obtain zirconium oxide (ZrO7).

The adsorption rate of phosphate ions of the obtained ZrO7 was determined in the same manner as in Example 1, and found to be 81%.

[0041]

Example 8 In each of 100 ml of an aqueous solution of calcium chloride in which 10.3 g of calcium chloride dihydrate was dissolved, Examples 1 to
5 g of each of the zirconium oxides ZrO1 to ZrO4 obtained in 4 was added to form a suspension. Subsequently, the pH of the suspension was adjusted to 9 with ammonium hydroxide, and stirring was continued overnight.
Thereafter, the resulting precipitate is filtered out, washed with water, and washed with calcium ion-exchanged zirconium oxide ZrO1 (C
a), ZrO2 (Ca), ZrO3 (Ca) and ZrO
4 (Ca) was obtained.

The phosphate ion adsorption rate of the obtained calcium ion-exchanged zirconium oxide was determined in the same manner as in Example 1 using a 0.01 W / V% Na2HPO4 aqueous solution adjusted to pH 3 with hydrochloric acid. (Ca) is 1
00%, ZrO2 (Ca) 35%, ZrO3 (Ca)
Was 55% and ZrO4 (Ca) was 75%.

[0043]

Example 9 148 g of zirconium oxychloride octahydrate and an aqueous solution of titanium tetrachloride (TiCl
₄ as 65.4%) 67 g and ammonium sulfate 27
After adding 3 g and dissolving, the mixture was heated and refluxed at 100 ° C. for 5 hours. One hour after the start of heating and refluxing, 15N ammonium hydroxide was gradually added dropwise to adjust the pH of the reaction solution to 2.5. The precipitate thus formed is filtered out, washed with water, dried at 60 ° C. and dried with zirconium-titanium oxide (Z
(r-TiO) was obtained.

The adsorption rate of phosphate ions of the obtained Zr-TiO was determined in the same manner as in Example 1 and found to be 100%.

[0045]

Comparative Example 1 A phosphate ion adsorption rate of a dried aluminum hydroxide gel (a product conforming to the Japanese Pharmacopoeia) was determined in the same manner as in Example 1. As a result, it was 21%.

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Claims (6)

(57) [Claims] 1. An acid-treated zirconium oxide obtained by hydrolyzing a zirconium salt and / or an alkaline earth
A phosphate ion adsorbent comprising a product treated with metal ions as an active ingredient. 2. A co-precipitate of zirconium oxide and titanium oxide obtained by hydrolyzing a zirconium salt and a titanium salt with an acid treatment and / or an alkaline earth metal ion treatment.
A phosphate ion adsorbent, characterized by containing the product as an active ingredient. Wherein the zirconium salt is the adsorbent of any one of claims 1 or 2 containing at least one of alkaline earth metal ions and oxoacid ions. 4. The adsorbent according to claim 2 , wherein the titanium salt contains at least one of an alkaline earth metal ion and an oxo acid ion. 5. The adsorbent according to claim 2, wherein the zirconium salt and the titanium salt contain at least one of an alkaline earth metal ion and an oxo acid ion. 6. hyperphosphorylated blood, characterized by containing as an active ingredient an adsorbent according to any one of claims 1 to 5
Adsorbent for the treatment of sickness .