JPH0422618B2 - - Google Patents

Description

[Detailed Description of the Invention] [Technical Field of the Invention] The present invention provides activated carbon such as spherical or granular activated carbon, coconut shell carbon, granulated carbon, etc. obtained from petroleum-based or coal-based pitch, organic synthetic polymers, etc. MgO
-Relates to an adsorbent impregnated with (supported by) a TiO ₂ composite. [Technical background of the invention] In patients with kidney or liver dysfunction, the ability to excrete metabolic waste products from the body is insufficient, and these substances accumulate in the body, resulting in various physiological disorders. It is occurring. Therefore, in order to improve the pathological conditions of these functionally impaired individuals, metabolic waste products and the like are generally removed from the living body. For example, patients with renal failure are known to be typical of patients with renal dysfunction;
Treatment methods include blood purification using a dialysis membrane and blood perfusion using activated carbon. Incidentally, patients with renal failure have a problem of hyperphosphatemia due to a decline in the ability to excrete phosphorus into the urine, but the conventional treatment methods described above cannot improve the pathology of hyperphosphatemia. There is. That is, the former blood purification method using a dialysis membrane cannot sufficiently suppress the phosphorus concentration in the blood, and is completely powerless against intestinal absorption of phosphorus, which is the most important factor in hyperphosphatemia. On the other hand, the latter treatment method using activated carbon has a problem due to the characteristics of activated carbon itself, that is, its adsorption power for inorganic substances such as phosphorus is extremely poor. [Purpose of the Invention] In view of the above-mentioned circumstances, the inventors of the present invention have conducted extensive studies with the aim of providing a new adsorbent that has excellent phosphorus adsorption properties without impairing the adsorption performance of activated carbon. It has been discovered that an adsorbent impregnated with a -TiO ₂ composite is extremely suitable for this purpose, leading to the completion of the present invention. [Structure and Effects of the Invention] Based on the above knowledge, the present invention provides activated carbon with MgO-
The present invention relates to an adsorbent impregnated with a TiO ₂ composite (hereinafter referred to as the adsorbent of the present invention). The present inventors filed an application on the same day to use the MgO-TiO ₂ composite as an antihyperphosphatemia agent because it has selective adsorption properties for phosphorus. The present invention is a further development of the adsorbent filed on the same day. That is, the adsorbent of the present invention retains the organic matter removal ability of activated carbon and also has phosphorus removal ability. Therefore, the adsorbent of the present invention is extremely effective for blood perfusion or as an oral drug for treating renal diseases. [Disclosure of the Invention] The present invention will be described in detail below. The activated carbon according to the present invention may be granulated carbon obtained by hardening coconut shell carbon or powdered carbon with a binder, or spherical activated carbon made from pitch and/or organic synthetic polymers. Spherical activated carbon is disclosed in, for example, Japanese Patent Publication No. 50-18879,
It can be produced by the production method disclosed in JP-A-56-69214 and JP-A-54-105897. Further, as the raw organic synthetic polymers, thermosetting resins such as phenol resins and epoxy resins, or thermoplastic resins such as styrene resins, vinylidene chloride resins, and copolymer resins thereof can be used. The activated carbon used in the present invention has a spherical shape in terms of durability and shape retention, and has an average particle size of 0.1 to 1 mm.
Preferably, spherical activated carbon has a specific surface area of 500 to 2000 m ² /g, a radius of 100 to 75000 Å, and a pore volume of 0.1 to 1.0 cm ³ /g. MgO impregnated on activated carbon in the present invention
-TiO ₂ composites preferably have the following properties in terms of phosphorus adsorption performance. (i) Composition ratio (molar ratio): MgO/TiO ₂ =99.99/
0.01 to 80/20 preferably 99.9/0.1 to 90/10 (ii) Crystal structure: In powder X-ray diffraction, MgO
The crystal diffraction pattern of The adsorbent of the present invention is manufactured as follows. After mixing and water-solubilizing magnesium and titanium alkoxides in an acid solution such as nitric acid, and soaking activated carbon,
An adsorption precursor is obtained by hydrolysis with an alkali such as aqueous ammonia or urea. The adsorption precursor is calcined to obtain the adsorbent of the present invention. Although the firing conditions vary somewhat depending on the preparation method, preparation conditions, blending ratio, etc., a temperature of usually 200 to 1000°C, preferably 300 to 700°C, and more preferably 350 to 500°C is suitable. The adsorbent of the present invention is MgO−TiO ₂
Preferably, 1 to 10% by weight of the composite is attached. When the amount of impregnation is less than 1% by weight, the effect of adsorption on phosphorus is small, and when it is more than 10% by weight, there is no significant improvement in the amount of phosphorus adsorbed as the amount of impregnation increases. Note that the precursor can also be produced by the following method.
That is, a method in which the activated carbon is immersed in a mixed aqueous solution of salts of magnesium and titanium, and then hydrolyzed with an alkali such as aqueous ammonia, a homogeneous co-precipitation method using urea in place of aqueous ammonia, or a method in which one of the metals is This is a method in which the activated carbon is immersed in an aqueous solution of a salt, then immersed in an aqueous solution of the other metal salt, and then hydrolyzed with aqueous ammonia or the like. When impregnating the metal composite, the activated carbon may be surface-treated with nitric acid or air beforehand. The firing process converts the precursor into a composite and adjusts the surface chemical properties. In the MgO-TiO ₂ composite constituting the adsorbent of the present invention, as the ratio of TiO ₂ increases, the crystallinity becomes disordered, the X-ray diffraction pattern unique to MgO disappears, and at the same time, the phosphorus adsorption performance decreases. When the ratio of TiO ₂ is low, it becomes difficult to distinguish from magnesium oxide alone in terms of X-ray diffraction. however,
In contrast to magnesium oxide adsorbents whose adsorption performance deteriorates over time due to the influence of carbon dioxide in the atmosphere, the adsorbent of the present invention maintains stable adsorption performance over a long period of time even in the air. The adsorbent of the present invention has an excellent ability to adsorb phosphorus components such as phosphate ions, and also has the adsorption properties of activated carbon, such as the ability to remove organic substances such as creatinine. That is, it is useful for treating hyperphosphatemia by adsorbing phosphorus components, and is also useful as an adsorbent for blood perfusion because it has the ability to adsorb and remove uremic metabolites such as creatinine. Further, as a method of use, the adsorbent of the present invention can be used by coating it with a polymer such as gelatin, albumin, or poly-2-hydroxyethyl methacrylate. It can also be used in combination with other adsorbents or in combination with other dialysis treatments. Furthermore, it can be used alone or in the form of a pharmaceutical composition as an oral adsorbent for the purpose of orally administering and removing phosphorus in the digestive tract. In this case, the adsorbent of the present invention is a composition with a pharmaceutically acceptable carrier and/or auxiliary agent, and is prepared in the form of a tablet, sublingual tablet, capsule, troche, or aqueous or oily solvent, suspension, emulsion, or syrup. It can be used in various forms such as agents and gelling agents. For tablets, capsules, etc., enteric-coated dosage forms may also be included in the present invention. Furthermore, when preparing the above formulation, pharmaceutical auxiliaries such as sweeteners, flavorants, coloring agents, preservatives, salts for adjusting osmotic pressure, and buffering agents can be used as necessary. The adsorbent of the present invention, which is made by impregnating activated carbon with 8.9% by weight of MgO-TiO ₂ composite, was used in Jcl-SD rats.
No abnormalities were observed in acute toxicity when 15,000 mg/Kg was orally administered. Although the content of the adsorbent of the present invention in the formulation composition may vary as appropriate, it can be contained in the range of 1% to 99% by weight, preferably 70% to 99% by weight. The dosage varies depending on the severity of the disease, etc.
Usually as activated carbon impregnated with MgO-TiO ₂ composite
0.5-10g/time, about 3 times a day, is appropriate. Of course, this does not apply in cases of emergency. Moreover, the timing of administration is not particularly limited, such as the storage period before dialysis or the dialysis period. Hereinafter, the present invention will be explained in detail with reference to Examples. Activated carbon production example Pitch obtained by thermal decomposition of petroleum and an organic solvent compatible with the pitch are mixed, and the pitch-organic solvent mixture is melted and dispersed using water containing a suspension as a dispersion medium. Remove the solvent from the spherical particles,
Then, by infusible carbonization and activation at 900°C, the particles have an average particle diameter of 0.4 mm, a specific surface area (methanol adsorption method) of 1200 m ² /g, and a pore volume of 100 to 75000 Å in radius (mercury intrusion method) 0.3 cm ³ /g of spherical activated carbon was obtained. Example 1 0.22 g of titanium tetraisopropoxide [(CH ₃ ) ₂ CHO] ₄ Ti was added to stirred water, the resulting precipitate was filtered, thoroughly washed with water, dispersed in 2 ml of water, and diluted with nitric acid (61 % by weight) was added and dissolved.
This solution was then added with 20 g of magnesium nitrate, Mg
A solution of (NO ₃ ) ₂ ·6H ₂ O dissolved in 9 ml of water was added to prepare a magnesium/titanium mixed solution. 10 g of the spherical activated carbon produced in the activated carbon production example was added to the mixed solution and stirred at 50° C. for 2 hours. The spherical activated carbon was separated and dried at 80° C. for 4 hours, then poured into 50 ml of 20% ammonia water and stirred for 6 hours. Next, the spherical activated carbon was separated, thoroughly washed with water, and then heated to 400°C at a rate of 200°C/hr in a nitrogen stream.
After holding at 400℃ for 1 hour, cool it and turn it into activated carbon.
10.89 g (impregnated amount: 8.9%) of an adsorbent impregnated with a MgO-TiO ₂ composite (molar ratio 99/1) was obtained. Example 2 After adding 8 ml of water to the magnesium/titanium mixed solution prepared in Example 1, 10 g of the spherical activated carbon produced in the activated carbon production example was added and stirred at 50°C for 2 hours. After separating the spherical activated carbon and drying it at 80°C for 4 hours, it was poured into 50 ml of 20% aqueous ammonia and stirred for 6 hours. Next, the spherical activated carbon was separated, thoroughly washed with water, and then heated to 400°C at a rate of 200°C/hr in a nitrogen stream.
After holding at 400℃ for 1 hour, cool it and turn it into activated carbon.
10.66 g (impregnated amount: 6.6%) of an adsorbent impregnated with a MgO-TiO ₂ composite (molar ratio 99/1) was obtained. Example 3 After adding 23 ml of water to the magnesium/titanium mixed solution prepared in Example 1, 10 g of the spherical activated carbon produced in the activated carbon production example was added and stirred at 50°C for 2 hours. After separating the spherical activated carbon and drying it at 80°C for 4 hours, it was poured into 50 ml of 20% aqueous ammonia and stirred for 6 hours. Next, the spherical activated carbon was separated, thoroughly washed with water, and then heated to 400°C at a rate of 200°C/hr in a nitrogen stream.
After holding at 400℃ for 1 hour, cool it and turn it into activated carbon.
10.47 g (impregnated amount: 4.7%) of an adsorbent impregnated with a MgO-TiO ₂ composite (molar ratio 99/1) was obtained. Example 4 NaH ₂ PO ₄ .2H ₂ O was added to human serum to adjust the phosphorus concentration to 10.1 mg/dl, and creatinine was further added to adjust the creatinine concentration to 9.8 mg/dl. Example 1: Take 10 ml of the serum into each stoppered Erlenmeyer flask.
After adding the adsorbent obtained in 3 to 3 and 0.5 g of spherical activated carbon produced in the activated carbon production example and shaking at 37°C for 2 hours, the supernatant serum was collected, and the phosphorus concentration was determined to be RaBA-
Mark (manufactured by Kyoto Daiichi Kagaku), and the creatinine concentration was measured by a Beckman creatinine analyzer (manufactured by Beckman). The results are shown in Table 1. 【table】

Claims (1)

[Claims] 1. An adsorbent for the treatment of renal diseases, which is made by impregnating activated carbon with a MgO-TiO ₂ composite. 2. The adsorbent according to claim 1, wherein the activated carbon is spherical activated carbon. 3. The adsorbent according to claim 1, wherein the MgO/TiO ₂ ratio of the MgO-TiO ₂ composite is 99.99/0.01 to 80/20 in molar ratio. 4 MgO-TiO ₂ composite to activated carbon 1% to 10% by weight
% by weight of the adsorbent according to claim 1. 5 Spherical activated carbon has an average particle size of 0.1 to 1 mm and a specific surface area.
Pore volume of 500-2000m ² /g, radius 100-75000Å
The adsorbent according to claim 2, which has a characteristic of 0.1 to 1.0 cm ³ /g. 6. The adsorbent according to claim 1, which is an antihyperphosphatemic agent. 7 Claim 1 which is an adsorbent for blood perfusion
Adsorbent as described in section.