JP5146643B2 - Orally administered adsorbent with excellent adsorption characteristics of nitrogen-containing compounds and method for producing the same - Google Patents

Description

  The present invention relates to an orally administered adsorbent having excellent adsorption characteristics of nitrogen-containing compounds. More specifically, the present invention relates to oral administration of nitrogen-containing compounds accumulated in a living body when kidney function is reduced in humans, livestock, etc. The present invention relates to an orally administered adsorbent that can be effectively adsorbed and removed by administration.

  Nitrogen-containing compounds such as urea, creatinine, and uric acid are found as products of protein metabolism in domestic animals such as pigs, chickens, cows, and sheep, pets such as dogs and cats (hereinafter referred to as domestic animals), and human excreta. Is contained in the excreta. Such nitrogen-containing compounds are produced and excreted by the filtration and separation function of the kidney, thereby avoiding the accumulation of toxic substances and unnecessary substances in the living body, and adjusting body fluid osmotic pressure and acid-base equilibrium. It has been broken. Accordingly, when the renal function is lowered, the nitrogen-containing compounds as described above accumulate in the living body, which causes damage to the living body such as uremia and impaired consciousness.

  Among the nitrogen-containing compounds described above, creatinine is a useful indicator substance for renal function because urinary content is almost constant, and serum creatinine level is measured.

  Activated carbon is known as a drug that removes the above nitrogen-containing compounds accumulated in the living body when renal function is reduced. For example, Patent Document 1 discloses that activated carbon is converted from carboxylic acid or a salt thereof. A creatinine adsorbent formed by coating a compound is proposed.

In addition, the present applicants previously proposed an orally administered adsorbent composed of clay particles having a layered structure with a cation exchange capacity of 50 milli-quivalent / 100 g or more (see Patent Document 2).
Japanese Patent Laid-Open No. 62-112564 JP 2006-89466 A

  However, the activated carbon-based adsorbent disclosed in Patent Document 1 is mainly used at the time of dialysis and is not suitable for oral administration. For example, such an adsorbent is a black powder, not only looks bad, but also easily causes constipation and other problems, and its adsorbing power is still not sufficient. In addition, when used for pets such as cats, there is a disadvantage that the bite by pets is poor.

  In patients with severe renal insufficiency, animals such as dogs and cats, a part of the toxin component consisting of various nitrogen-containing compounds that cannot be excreted as urine is passed through the intestinal mucosa (creatinine). , BUN, etc.) are adsorbed and discharged out of the body together with defecation, but the activated carbon-based adsorbent also has room for improvement in terms of such discharge characteristics.

  On the other hand, the clay-based adsorbent proposed in Patent Document 2 is one in which the disadvantages of the above-mentioned activated carbon-based adsorbent are effectively improved. There was a problem that it was easy to elute in the body. In other words, it is known that accumulation of aluminum in the body may cause health problems such as aluminum encephalopathy (dialysis dementia) and aluminum osteopathy. For some patients, the use of aluminum-containing medication is restricted. Therefore, it is preferable to avoid such an agent that elutes aluminum in the body even for pets.

  Accordingly, an object of the present invention is to provide a clay-based orally administered adsorbent in which nitrogen-containing compounds such as creatinine can be effectively adsorbed and removed by oral administration and the dissolution of aluminum in the body is effectively suppressed. is there.

  The inventors of the present invention have been able to effectively adsorb and remove nitrogen-containing compounds obtained by appropriately acid-treating certain clay minerals, and that the elution is effectively suppressed while containing aluminum. The present invention was completed.

According to the present invention, it is composed of activated clay obtained by acid treatment of dioctahedral smectite clay, the weighted surface area average particle diameter measured by laser diffraction scattering method is 10 to 700 μm, and the specific surface area is 100 to 400 m. ^{2 /} g Ri range near the and oral administration adsorbent angle of repose, characterized in der Rukoto 40 degrees or less is provided.

According to the present invention, the dioctahedral smectite clay is acid-treated using a mineral acid aqueous solution, and washed with water after the acid treatment to produce an orally administered adsorbent composed of activated clay.
Including a step of adjusting the weighted surface area average particle size measured by the laser diffraction scattering method to a range of 10 to 700 μm by a non-destructive means at any stage before the acid treatment or after washing with water. A method for producing an orally administered adsorbent is provided.

In the production method of the present invention,
(1) The particle size adjustment by the non-destructive means is performed by spray granulation or rolling granulation,
(2) performing the acid treatment by adding a mineral acid to an acid concentration of 20 to 45% by weight and heating to a temperature of 80 ° C. or higher;
Is preferred.

  The orally administered adsorbent of the present invention, as shown in the examples described later, exhibits a high adsorbability equivalent to or higher than that of activated carbon with respect to nitrogen-containing compounds, particularly creatinine and uric acid. It is extremely useful as a therapeutic or prophylactic agent for this. Moreover, the activated clay particles constituting the adsorbent are basically natural aluminosilicates, have hydrophilicity, and are also approved as food additives. Therefore, there is a possibility that it can be effectively applied not only to livestock but also to humans. It is particularly useful as an additive for animal pet foods.

  Moreover, it is important that the orally administered adsorbent of the present invention has an aluminum elution amount of 1 measured using a model gastric fluid (buffer solution having a pH of 1.5) as shown in the examples described later. Very small, 0.0 mg / g or less. In other words, in the present invention, while aluminum is contained, elution of aluminum in the body is effectively suppressed, which is a great difference from conventionally known clay-based adsorbents.

  Further, since the orally administered adsorbent of the present invention exhibits an excellent adsorptivity to uric acid as well as conventional clay-based adsorbents, it can be applied to, for example, gout prevention and treatment techniques. Can also be used.

<Orally administered adsorbent>
As already described, the orally administered adsorbent of the present invention comprises an activated clay obtained by acid treatment of dioctahedral smectite clay. That is, in such activated clay, the aluminum component coexisting with the smectite is effectively removed, and the remaining aluminum component is incorporated in a stable form in the smectite crystal structure. For this reason, although it contains an aluminum component, it has the property that elution of aluminum in a living body is effectively suppressed.

In addition, dioctahedral smectite clay treated with acid is considered to have been transformed from volcanic rocks and lava under the influence of seawater. (Iii) where the main component is smectite, which consists SiO ₄ tetrahedral layers -AlO ₆ octahedral layer -SiO ₄ tetrahedra layer, and these tetrahedral layer and the octahedral layer are isomorphous replacement with partially different metals The layer structure is a basic structure (unit layer), and cations such as Ca, K, Na, and hydrogen ions and water molecules coordinated with them exist between the stacked layers of such a three-layer structure. . In addition, since part of Al in the octahedral layer of the three-layer structure is replaced with Mg or divalent Fe, and part of Si in the tetrahedral layer is replaced with Al, the crystal lattice has a negative charge. This negative charge is neutralized by metal cations and hydrogen ions present between the unit layers. Such smectite clays include acid clay, bentonite, fuller's earth, and the like, and exhibit different characteristics depending on the type and amount of metal cations existing between unit layers, the amount of hydrogen ions, and the like. For example, in bentonite, the amount of Na ions existing between unit layers is large, and therefore, the pH of a dispersion suspended and dispersed in water is high, generally on the high alkali side, and has high swellability with respect to water. Furthermore, it shows the property of gelling and solidifying. On the other hand, in the acid clay, the amount of hydrogen ions present between the unit layers is large, and therefore the pH of the dispersion suspended and dispersed in water is low, generally on the acidic side, and also exhibits swelling properties with respect to water. However, compared with bentonite, its swelling property is generally low, and it does not cause gelation.

  As described above, the dioctahedral smectite clay exhibits different characteristics depending on the type of metal cation existing between the unit layers. However, the activated clay used in the present invention is acid-treated and the metal cation existing between the unit layers. Most of these are replaced by hydrogen ions. Accordingly, the dioctahedral smectite clay used for the production of the activated clay is not particularly limited, and any one can be used. For example, the clay may be acidic clay or bentonite. .

Thus, the activated clay used as the orally administered adsorbent in the present invention is obtained by acid treatment of the smectite clay as described above, and has the following formula:
Al ₂ O ₃ / SiO ₂ = 5.9 × 10 ^{−2 to} 0.12
R ₂ O / SiO ₂ = 2.0 × 10 ^{−3 to} 2.7 × 10 ⁻²
MO / SiO ₂ = 2.0 × 10 ^{−2 to} 0.11
(In the above formula, R is an alkali metal and M is an alkaline earth metal)
It has the molar composition represented by these. That is, the Al ₂ O ₃ / SiO ₂ molar ratio is relatively small, and the R ₂ O / SiO ₂ molar ratio and the MO / SiO ₂ molar ratio are considerably smaller than the smectite clay before acid treatment. This is because the aluminum component, alkali metal component, and alkaline earth component are considerably removed by the acid treatment.

  Further, in the present invention, the acid treatment as described above is performed to such an extent that an aluminum component that can be easily eluted by gastric juice is removed, but the degree is such that the layer structure peculiar to smectite is maintained. For example, the activated clay obtained by the present invention has an X-ray diffraction peak derived from the [001] plane peculiar to smectite in the region of 2θ = 3 to 10 degrees. When the relative area intensity ratio of the peak when the diffraction peak area of the [001] plane of standard smectite is 100% is the smectite content, the smectite content of the orally administered adsorbent of the present invention is preferably 1 to 12%. Is in the range of 2 to 10% or more.

  That is, smectite clay is derived from its unique layer structure, and has a cation exchange capacity and a proton releasing ability (see Patent Document 2). Therefore, a toxin component composed of various nitrogen-containing compounds, for example, In addition to exhibiting excellent adsorptivity to creatinine and uric acid, it is hydrophilic per se, and thus exhibits no inconvenience such as constipation even when administered orally. In addition, smectite clay exhibits a high negative ζ potential in the region where the pH is 4.8 or higher, and therefore, molecules of nitrogen-containing compounds such as creatinine and urea are allowed to enter the intestinal environment (pH is neutral or weakly alkaline). It also exhibits the property of being adsorbed by hydrogen bonding or dipole interaction.

  As understood from the above description, the activated clay obtained by the present invention has a characteristic that it can adsorb nitrogen-containing compounds such as creatinine and urea because the structure peculiar to smectite clay remains to some extent. For example, when the X-ray diffraction peak area of the above-mentioned [001] plane is smaller than the above range, the acid treatment is performed more than necessary, and the adsorptivity to the nitrogen-containing compound is unsatisfactory. (In an extreme case, it becomes the same level as silica), and when it is larger than the above range, the acid treatment is insufficient and the amount of aluminum elution is increased. Become.

  The activated clay used as an orally administered adsorbent in the present invention also needs to have a relatively coarse particle size, specifically, weighted surface area average particles measured by a laser diffraction scattering method. The diameter is 10 to 700 μm, preferably 10 to 100 μm. The average particle diameter of the present invention is a weighted surface area average particle diameter (Sauter diameter, body area average diameter) defined in JIS-Z-8819-2. Moreover, it is preferable that the fine particle content of 5 μm or less is suppressed to a range of 12% by volume or less from the particle size distribution under the volume-based sieve. That is, by having such a relatively coarse particle diameter, the aluminum elution amount can be suppressed without impairing the adsorptivity to the nitrogen-containing compound. As understood from the above description, in the activated clay obtained by the present invention, since the unit layer structure of smectite remains, the aluminum component also remains. Therefore, when the average particle diameter is smaller than the above range, the frequency of contact between these particles and gastric juice (gastric acid) becomes too high when administered orally, resulting in an increase in the amount of aluminum elution. is there. In addition, when the average particle size is larger than the above range, the adsorptivity to the nitrogen-containing compound is lowered, the biting property of the pet is also lowered, and oral administration to the pet may be difficult.

Furthermore, the activated clay obtained by the present invention has a specific surface area increased by acid treatment, and the specific surface area is in the range of 100 to 400 m ² / g, preferably 150 to 350 m ² / g. For this reason, the adsorptivity with respect to a nitrogen-containing compound is not impaired, but the adsorptivity equivalent to the smectite clay before acid treatment is shown. For example, when the specific surface area is larger than the above range, the acid treatment is usually performed more than necessary, and the adsorptivity to the nitrogen-containing compound derived from the smectite structure is lowered. Further, when the specific surface area is smaller than the above range, the acid treatment is usually insufficient, which causes a disadvantage that the amount of aluminum elution increases.

Activated clay used as oral adsorbents described above, from the viewpoint of reducing the aluminum dissolution amount, an angle of repose that is Ru der 40 degrees or less. In other words, this angle of repose is an angle formed by a plane and a horizontal plane when the free surface is in a critical stress state when the particles are stacked (JIS-R-1600). Therefore, if the angle of repose is in the above range, the particles are difficult to pile up. In other words, the particles of the activated clay are rounded, and the activated clay is subjected to a force such as compression, impact, shear, friction, cutting, etc. This indicates that the particle size was not adjusted, and that the new fracture surface was not exposed. In the present invention, by using the activated clay showing such an angle of repose, the surface exposure of the aluminum component is suppressed, and the aluminum elution amount can be more effectively suppressed.

  As described above, since the orally administered adsorbent of the present invention effectively suppresses aluminum elution due to gastric acid and the like, it can effectively avoid accumulation of aluminum in the body by oral administration, and by oral administration, renal Toxins such as uremia that are accumulated in the body due to reduced function, etc., produced in the intestine, excreted in the digestive tract by enterohepatic circulation, or secreted from the intestinal wall as a kind of dialysis membrane Components and precursors of toxin components, such as creatinine, uric acid, indoxyl sulfate, methylguanidine, etc. can be adsorbed in the digestive tract and excreted out of the body together with feces. In particular, it acts effectively on creatinine and uric acid, adsorbs them and excretes them from the body.

For example, creatinine is a nitrogen-containing cyclic compound that can exhibit keto-enol tautomerism as shown in the following formula (1), and uric acid as shown in the following formula (2). Adsorption is almost 100%.

  Moreover, the activated clay used as an orally administered adsorbent is an acid-treated product of smectite clay, which is a natural aluminosilicate, which is not only approved as a food additive, but also has a low MgO content due to its chemical composition, Since these components are rarely extracted, it is difficult to serve as a source of Mg for Struvite, which is one of the crystals precipitated from urine, and has an advantage of exhibiting a stable adsorption action in the intestine.

<Manufacture of activated clay>
In the present invention, the activated clay described above is produced by subjecting the above-mentioned various dioctahedral smectite clays to acid treatment using a mineral acid aqueous solution and washing with water after the acid treatment. In any stage before the acid treatment or after the water treatment after the acid treatment, the particles in the slurry have a weighted surface area average particle diameter of 10 to 700 μm, preferably 10 to It is important to adjust the particle size so as to be in the range of 100 μm. Here, particle size adjustment by non-destructive means means granulation by a method of increasing the particle size by agglomeration of powder or coating of the surface of solid particles without using physical means accompanied by shearing force such as grinding. For example, rolling granulation, fluidized bed granulation, and spray granulation correspond to this. That is, by adjusting the particle size by such means, it is possible to obtain activated clay particles having the above-mentioned particle size without generating a new fracture surface, and such particles have, for example, the angle of repose described above. Thus, the amount of aluminum elution can be significantly reduced. In addition, those adjusted to the average particle size as described above by such a method generally have a fine particle content of 5 μm or less within the above-mentioned range of 12% by volume or less from the particle size distribution under the volume-based sieve. As an example, the sample obtained in Example 1 had a weighted surface area average particle size of 14 μm and a fine particle content of 6%.
Hereinafter, the manufacturing process will be described in consideration of such particle size adjusting means.

  First, the smectite clay used as a raw material is subjected to refining operations such as stone sand separation, buoyancy beneficiation, magnetic beneficiation, water tank, wind drought, etc., if necessary, and then acid treatment, but prior to acid treatment, As stated, the particle size can be adjusted by non-destructive means such as rolling granulation or spray granulation. In addition, when such particle size adjustment is performed after washing with water after acid treatment, moderate coarse particles (for example, weights) are obtained by ordinary destructive means, for example, pulverization using a pulverizer such as a ball mill. It is preferable that the particle size is preliminarily adjusted to a surface area average particle diameter of about 10 to 700 μm. That is, if the clay particle size at this time is larger than necessary, it may be difficult to perform the acid treatment uniformly.

  When the particle size is adjusted to the above-described range by rolling granulation, a clay lump may be put into the granulator and sprayed with water while rolling the lump. On the other hand, in the case of spray granulation, a slurry in which raw clay is dispersed in water is prepared (usually about 1 to 15% by weight), and this slurry is sprayed to adjust the particle size to the above-mentioned range. it can. In this case, the particle diameter can be adjusted by the slurry concentration, spraying pressure, etc., but when bentonite is used as the raw clay, if the slurry concentration is too high, particle swelling and gelation will occur. Such inconvenience can be avoided because the slurry concentration when granulating is considerably low.

  The acid treatment is performed using a mineral acid such as sulfuric acid, hydrochloric acid, nitric acid, etc., but sulfuric acid is most preferably used from the viewpoints of handleability and acid treatment speed. Further, such a mineral acid is mixed with the above clay particles (or an aqueous slurry of clay particles) so as to have an acid concentration of 20 to 45% by weight, and in the range of 80 ° C. or higher, particularly 85 to 95 ° C. It is preferable to carry out the acid treatment by heating. That is, by performing the acid treatment under such conditions, the aluminum component and the like are removed while maintaining the structure peculiar to the smectite clay as described above by the treatment in an appropriate time (about 1 to 20 hours). Because it can be done. For example, if the acid treatment is performed in a range that does not satisfy the above conditions, it takes more time than necessary for an appropriate acid treatment, or the acid treatment proceeds rapidly, and the control becomes difficult. Because there is a fear.

  After the acid treatment as described above, washing with water is performed to remove the acid and unnecessary salts generated by the acid treatment.

  In this case, if the particle size is adjusted before the acid treatment, the particle size is substantially maintained as it is in the acid treatment step, so that it can be immediately dried to obtain a product. Such drying can be performed by any means such as hot air drying.

  On the other hand, when only preliminary particle size adjustment is performed before the acid treatment, the particle size adjustment is performed in the above-described range by non-destructive means after washing with water. In this case, nondestructive particle size adjustment is performed by rolling granulation or spray granulation.

  The activated clay particles thus obtained have the composition, particle size distribution and specific surface area described above, have excellent adsorptivity to nitrogen-containing compounds such as creatinine and uric acid, and also have a reduced aluminum elution amount. As an orally administered adsorbent, it is used in humans and pets to remove toxin components consisting of nitrogen-containing compounds.

  In addition, the orally administered adsorbent of the present invention can be used as a therapeutic / preventive agent for urinary stone disease by using it in admixture with edible organic acids or salts thereof approved as food additives, if necessary. It can also be provided, and can also be used in combination with calcium carbonate to increase antacidity. However, mixing with other components is limited to methods that do not generate new fracture surfaces. Therefore, the orally administered adsorbent of the present invention is most preferably used alone without being mixed with other components.

(1) Particle size distribution measurement With the Mastersizer Hydro 2000G laser diffraction particle size distribution analyzer, water is used as the dispersion medium, the sample is added and the particle size distribution is obtained without prior dispersion under the conditions of a pump speed of 2000 rpm, a stirring speed of 500 rpm, and a tip movement of 50%. It was measured. Calculate the particle size distribution (volume%) of 5μm or less and the weighted surface area average particle size (D [3,2]) specified in JIS-Z-8819-2 from the obtained particle size distribution under the volume-based sieve. did.

(2) Specific surface area A Sorptomatic Series 1900 manufactured by Carlo Elba was used to measure the nitrogen adsorption isotherm. The specific surface area was determined by the BET method from the adsorption side nitrogen adsorption isotherm with a specific pressure of 0.2 or less.

(3) Angle of repose The angle of repose was measured using a powder tester PT-R manufactured by Hosokawa Micron Corporation.

(4) Smectite content rate A 10 vol% ethylene glycol / ethanol solution is added to 1 g of a sample and dried at 50 ° C. overnight. The obtained sample was measured using an X-ray diffractometer PW1830 manufactured by Nippon Philips Co., Ltd.
Target Cu
Filter Ni
Detector proportional counter voltage 40KVP
Current 50mA
Scanning speed 1 ° / min
Slit DS: 1/4 ° RS: 0.1 mm SS: 1/4 °
Irradiation angle 6 °
Scanning range 3-10 °
The smectite content was expressed as the relative area intensity ratio (%) of each sample, with the peak area of the X-ray diffraction pattern of the Japan Clay Society standard clay sample JCSS-3101 as 100%.

(5) Creatinine adsorption test To each 400 mg of the sample, 0.5 mL of a standard solution having a concentration of 0.1 g / L was added, and 3.0 mL of pH 6.86 buffer was added and shaken. The mixture was allowed to stand at room temperature for 10 minutes and then centrifuged at 2500 rpm for 15 minutes.
2.0 mL of the supernatant was collected and placed in a 30 ° C. water bath. Picric acid test solution (8.7 mmol / L) and 0.75N sodium hydroxide solution were added in an amount of 1.0 mL each and stirred. After being left in a 30 ° C. water bath for 20 minutes, the absorbance at 505 nm was measured.

(6) Al dissolution test
41.4 mL of 1N-HCl was collected, 3.73 g of KCl was added, and 0.5 g of a sample was added to 25 mL of model gastric fluid prepared by measuring up to 1000 mL. Using an Eyela Shaker “MINI” SS-80 installed in a thermostatic chamber, it was shaken at 37 ° C. for 5 hours on a scale 5. The Al concentration in the supernatant obtained by centrifugation at 2500 rpm for 15 minutes was measured with an atomic absorption photometer.

Example 1
The acid clay from Haguroyama, Niigata Prefecture, was crushed with a meat puller and granulated using a rolling granulator (referred to as granulated product A). To 40.7 g of this granulated product A, 45.6 g of 75% sulfuric acid and 72 ml of water were added to prepare a slurry. Heated at 90 ° C. for 6 hours with occasional mixing. Then, it filtered, washed with water so that a basic component might not precipitate, and dried at 110 degreeC overnight, and the sample was obtained. This was a fine particle with good fluidity. The physical properties were measured and the results are shown in Table 1.

(Example 2)
A slurry was prepared by adding 27.7 g of 75% sulfuric acid and 67 ml of water to 33.4 g of the granulated product A obtained in Example 1. Thereafter, the same procedure as in Example 1 was performed to obtain a sample. The physical properties were measured and the results are shown in Table 1.

(Example 3)
The acid white clay A from Odo, Shibata City, Niigata Prefecture was crushed with a meat puller. 1 kg of this acid clay was dispersed in 11 L of water and centrifuged to obtain a suspension having a solid content of 4.9%. This suspension was spray-dried to obtain 440 g of granules. Next, 750 mL of water and then 500 g of concentrated sulfuric acid (96%) are slowly added to a glass flask equipped with a 2 L stirring blade, and 200 g of the granules obtained above are further dispersed, and the mixture is heated to 90 ° C. over 2 hours. The temperature was raised and the temperature was maintained for 8 hours, and then cooled to 50 ° C. in 1 hour. This slurry was filtered under reduced pressure to recover the cake. Four liters of distilled water was added to this cake, and after reslurry, it was filtered. This washing operation was repeated three times. The collected cake was dried at 110 ° C. overnight. The weight after drying was 134 g. The physical properties were measured and the results are shown in Table 1.

Example 4
Using the acid clay from Niigata Prefecture's womb city as a raw material, this raw material was roughly crushed, kneaded and granulated to a diameter of 5 mm. Next, 150 g of granulated raw material clay with a solid content of 62% is added to 0.2 liter of 34 wt% sulfuric acid aqueous solution in a beaker, acid treatment is performed at 95 ° C. for 14 hours, and the product after washing with water after filtration and washing with water Got. It was passed through a 28 mesh sieve, adjusted to a moisture of 28%, and granulated with a rolling granulator to obtain a sample. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 1)
Galeon Earth V2 which is activated clay made by Mizusawa Chemical Co., Ltd. was used. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 2)
In Example 4, except that the concentration of the sulfuric acid aqueous solution was changed to 52% by weight and the acid treatment was changed to 95 ° C. for 24 hours, the water-washed product obtained in the same manner was dried and pulverized to obtain a sample. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 3)
Using the acid clay from Niigata Prefecture's womb city as a raw material, this raw material was roughly crushed, kneaded and granulated to a diameter of 5 mm. Next, 225 g of granulated raw material clay with a solid content of 62% is added to 0.15 liter of 12.5 wt% sulfuric acid aqueous solution in a beaker, acid treatment is performed at 90 ° C. for 15 hours, filtration, and washing with water after washing with water. I got a finished product. Next, this water-washed product was dispersed in water and adjusted to a solid content of 10%, then pulverized with a tube mill, sieved, and then filtered to obtain a sample by drying with a spin flash dryer. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 4)
Samples were obtained by molding acid clay B from Odo, Shibata City, Niigata Prefecture, with an extruder having a die with a hole diameter of 0.8 mm. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 5)
A sample was obtained by pulverizing acid clay B from Odo, Shibata City, Niigata Prefecture, with a mortar. The physical properties were measured and the results are shown in Table 1.

(Comparative Example 6)
Synthetic aluminum silicate conforming to the Japanese Pharmacopoeia was used. The physical properties were measured and the results are shown in Table 1.

Claims (4)

It consists of activated clay obtained by acid treatment of dioctahedral smectite clay, and has a weighted surface area average particle diameter of 10 to 700 μm and a specific surface area of 100 to 400 m ² / g as measured by a laser diffraction scattering method. Ah it is, and, oral adsorbents angle of repose, characterized in der Rukoto 40 degrees or less. In the method for producing an orally administered adsorbent consisting of activated clay by acid treatment of a dioctahedral smectite clay using an aqueous mineral acid solution and washing with water after the acid treatment,
Including a step of adjusting the weighted surface area average particle size measured by the laser diffraction scattering method to a range of 10 to 700 μm by a non-destructive means at any stage before the acid treatment or after washing with water. A method for producing an orally administered adsorbent. The production method according to claim 2 , wherein the particle size adjustment by the non-destructive means is performed by spray granulation or rolling granulation. The method according to claim 2 or 3 , wherein the acid treatment is performed by adding a mineral acid so as to have an acid concentration of 20 to 45% by weight and heating to a temperature of 80 ° C or higher.