Oral composition containing inorganic porous body

Abstract

An oral composition according to the present disclosure contains an inorganic porous body. When 11.8 g of the inorganic porous body, per 1 mmol of choline, is mixed for one hour at a concentration of 2 g / L to choline and a primary, secondary, or tertiary amine, or ammonia existing as a mixture in equimolar amounts in an artificial intestinal juice, the adsorption rate of the primary, secondary, or tertiary amine, or ammonia is 60.0% or more and the adsorption rate of the choline is 40.0% or less. Alternatively, an oral composition according to the present disclosure contains zeolite. The zeolite has an MFI structure and has a mole ratio of SiO2 of 30.0-130000.0 with respect to Al2O3, or the zeolite has an FER structure and has a mole ratio of SiO2 of 15.0-130000.0 with respect to Al2O3.

Description

Oral composition containing inorganic porous material The present disclosure relates to an inorganic porous material-containing oral composition formulated to selectively adsorb primary, secondary, or tertiary amines or ammonia relative to choline. Some primary, secondary and tertiary amines and ammonia exist as toxins in living organisms, and when they exist in excess in the living organism, they cause various diseases. For example, in trimethylaminuria (fish odor syndrome), trimethylamine (TMA) in body fluids is higher than in healthy people due to genetic deficiency of trimethylamine metabolic enzyme FMO3. Trimethylamine, a volatile component, is excreted in sweat, breath, urine, and other body fluids, causing a body odor similar to rotten fish, reducing the quality of life and social activity of trimethylaminuria patients, and even causing mental symptoms such as depression. There is no fundamental treatment, and symptomatic treatments are mainly used, such as dietary restrictions on foods that contain a lot of trimethylamine precursors such as choline, lecithin (phosphatidylcholine), carnitine, betaine (N,N,N-trimethylglycine), and trimethylamine-N-oxide (TMAO), and washing the body with acidic soap that can efficiently wash away trimethylamine, a basic substance. In addition, TMAO, a metabolite of trimethylamine, has been reported to be a causative agent of atherosclerosis, and has also been reported to be involved in coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's disease, obesity, advanced chronic kidney disease in patients with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, and colorectal cancer. In addition, it has been reported that histamine produced excessively by intestinal bacteria increases the histamine concentration in the digestive tract, activating H4 receptors and inducing abdominal pain in patients with irritable bowel syndrome. Furthermore, when the detoxification of ammonia to urea in the liver becomes insufficient due to liver failure, cirrhosis, portosystemic shunt, urea cycle disorder, organic acidemia, etc., an excess of ammonia in the circulating blood, i.e., hyperammonemia, is caused by hepatic encephalopathy. As in the above example, it is believed that by adsorbing and removing primary, secondary, and tertiary amines or ammonia that are present in excess as toxins or pathogenic substances, it is possible to detoxify poisoning and treat diseases, but the selectivity with choline, a basic organic molecule and nutrient with similar properties, becomes an issue. Choline is an essential nutrient for the body, and is particularly essential for growth. It has been reported that choline deficiency causes various diseases. Known materials (adsorbents) that adsorb and remove basic compounds from biological fluids, and more broadly from water, include activated carbon, cation exchange resins, clay minerals, inorganic porous bodies, metal organic frameworks (MOFs), etc. Choline, primary, secondary, and tertiary amines, and ammonia are all basic compounds, and when they exist as the same cationic species in water, it is difficult to distinguish between choline and primary, secondary, and tertiary amines or ammonia and adsorb them, and no such adsorbents are known. US Pat. No. 5,399,433 discloses the use of zeolite to treat trimethylaminuria. Some primary, secondary, and tertiary amines, ammonia, or their metabolites exist as toxins in the body, and when they are present in excess in the body, they cause various diseases. It is thought that primary, secondary, and tertiary amines or ammonia that exist in excess as toxins or pathogenic substances can be used to treat poisoning or diseases by adsorbing and removing them, but the problem with the adsorbent is that it simultaneously removes choline, a molecule with similar properties and a nutrient. Therefore, there is a need to selectively adsorb and remove primary, secondary, and tertiary amines or ammonia compared to choline. Patent Document 1 does not disclose any specific examples of adsorbing trimethylamine using zeolite, does not disclose selective adsorption of trimethylamine to zeolite relative to choline, and does not disclose specific characteristics of zeolite for this purpose, and does not pay any attention to the above-mentioned adsorption selectivity. US Patent Application Publication No. 2018 / 0200291 The present disclosure has been made in consideration of the above circumstances, and provides an oral composition which is safe and capable of selectively adsorbing and removing primary, secondary and tertiary amines, ammonia or metabolites thereof. Means for Solving the Problems The present inventors have conducted extensive research into adsorbents in order to solve the above problems, and as a result have discovered an inorganic porous material-containing oral composition that selectively adsorbs primary, secondary, and tertiary amines or ammonia compared to choline. The present disclosure has been completed based on the above findings. That is, the gist of the present disclosure includes the following. [1] A porous inorganic material, An oral composition, in which when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of primary, secondary, tertiary amine or ammonia is 60.0% or more and the adsorption rate of choline is 40.0% or less. [1-1] The composition for oral administration according to the above-mentioned [1], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of the primary, secondary, tertiary amine or ammonia is 70.0% or more and the adsorption rate of choline is 40.0% or less. [1-2] The composition for oral administration according to the above [1] or [1-1], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of the primary, secondary, tertiary amine or ammonia is 80.0% or more and the adsorption rate of choline is 40.0% or less. [1-3] The composition for oral administration according to any one of the above [1] to [1-2], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of the primary, secondary, tertiary amine or ammonia is 90.0% or more and the adsorption rate of choline is 40.0% or less. [1-4] The composition for oral administration according to the above [1] or [1-1], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of the primary, secondary, tertiary amine or ammonia is 70.0% or more and the adsorption rate of choline is 30.0% or less. [1-5] The composition for oral administration according to any one of the above [1] to [1-2], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of primary, secondary, tertiary amine or ammonia is 80.0% or more and the adsorption rate of choline is 20.0% or less. [1-6] The composition for oral administration according to any one of the above [1] to [1-3], wherein when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed for 1 hour at a concentration of 2 g / L with choline and primary, secondary, tertiary amine or ammonia present as a mixture in equimolar amounts in artificial intestinal juice, the adsorption rate of the primary, secondary, tertiary amine or ammonia is 90.0% or more and the adsorption rate of choline is 10.0% or less. [2] The composition for oral administration according to any one of the above [1] to [1-6], wherein the inorganic porous material has an adsorption rate for primary, secondary, or tertiary amines or ammonia that is 2.00 times or more higher than the adsorption rate for choline. [2-1] The composition for oral administration according to the above-mentioned [2], wherein the inorganic porous material has an adsorption rate for primary, secondary, or tertiary amines or ammonia that is 2.50 times or more higher than the adsorption rate for choline. [3] The composition for oral administration according to any one of the above [1] to [2-1], wherein the inorganic porous material is an aluminosilicate or a silicate. [4] The composition for oral administration described in the above [3], wherein the aluminosilicate is a zeolite. [5] The composition for oral administration according to the above-mentioned [4], wherein the maximum number of rings of the zeolite is 10, and the maximum spherical diameter of diffusion in pores is 3.68 Å or more. [5-1] The composition for oral administration according to the above [5], wherein the maximum number of rings of the zeolite is 10, and the maximum spherical diameter of diffusion in pores is 3.70 Å or more. [5-2] The composition for oral administration according to the above [5] or [5-1], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 3.75 Å or more. [5-3] The composition for oral administration according to any one of the above [5] to [5-2], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.22 Å or more. [5-4] The composition for oral administration according to any one of the above [5] to [5-3], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.50 Å or more. [5-5] The composition for oral administration according to any one of the above [5] to [5-4], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.65 Å or more. [5-6] The composition for oral administration according to any one of the above [5] to [5-5], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.69 Å or more. [5-7] The composition for oral administration according to any one of the above [5] to [5-6], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 4.91 Å or less. [5-8] The composition for oral administration according to any one of the above [5] to [5-7], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 4.90 Å or less. [5-9] The composition for oral administration according to any one of the above [5] to [5-8], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 4.85 Å or less. [5-10] The composition for oral administration according to any one of the above [5] to [5-9], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.80 Å or less. [5-11] The composition for oral administration according to any one of the above [5] to [5-10], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 4.75 Å or less. [5-12] The composition for oral administration according to any one of the above [5] to [5-11], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter of diffusion in pores of 4.73 Å or less. [5-13] The composition for oral administration according to any one of the above [5] to [5-12], wherein the zeolite has a maximum ring number of 10 and a maximum spherical diameter for diffusion in pores of 4.71 Å or less. [6] The composition for oral administration according to any one of the above [4] to [5-13], wherein the zeolite has an MFI structure or an FER structure. [6-1] The composition for oral administration described in the above [6], wherein the zeolite has an MFI structure. [7] The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to any one of the above [4] to [6-1], wherein the zeolite has a molar ratio of from 15.0 to 130,000.0. [7-1] The zeolite is Al ２ O ３ SiO ２ The composition for oral administration described in [7] above, wherein the zeolite has a molar ratio of from 18.0 to 129,000.0. [7-2] The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to the above-mentioned [7] or [7-1], wherein the zeolite has a molar ratio of from 30.0 to 129,000.0. [8] The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to any one of the above [7] to [7-2], wherein the zeolite has a molar ratio of from 30.0 to 80.0. [9] The outer surface area of ​​the zeolite is 33.0 m ２ The composition for oral administration according to any one of the above [4] to [8], wherein the oral composition has a molecular weight of less than 1000 mg / g. [9-1] The outer surface area of ​​the zeolite is 30.0 m ２ The composition for oral administration according to any one of the above [4] to [9], wherein the oral composition has a molecular weight of less than 1000 mg / g. [9-2] The outer surface area of ​​the zeolite is 26.0 m ２ The composition for oral administration according to any one of the above [4] to [9-1], wherein the oral composition has a molecular weight of less than 1000 mg / g. [9-3] The outer surface area of ​​the zeolite is 20.0 m ２ The composition for oral administration according to any one of the above [4] to [9-2], wherein the oral composition is 0.01 to 0.01g / g or less. [9-4] The outer surface area of ​​the zeolite is 15.0 m ２ The composition for oral administration according to any one of the above [4] to [9-3], wherein the oral composition is 0.01 to 0.01g / g or less. [9-5] The outer surface area of ​​the zeolite is 13.3 m ２ The composition for oral administration according to any one of the above [4] to [9-4], wherein the oral composition is 0.01 to 0.01g / g or less. [9-6] The composition for oral administration according to any one of the above [4] to [9-5], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1800° or less. [9-7] The composition for oral administration according to any one of the above [4] to [9-6], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1500° or less. [9-8] The composition for oral administration according to any one of the above [4] to [9-7], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1300° or less. [9-9] The composition for oral administration according to any one of the above [4] to [9-8], wherein the zeolite has a median diameter of 5.5 μm or more. [9-10] The composition for oral administration according to any one of the above [4] to [9-9], wherein the zeolite has a median diameter of 10.0 μm or more. [9-11] The composition for oral administration according to any one of the above [4] to [9-10], wherein the zeolite has a median diameter of 11.7 μm or more. [9-12] The composition for oral administration according to any one of the above [4] to [9-11], wherein the zeolite has a cumulative frequency 10% diameter of 2.5 μm or more. [9-13] The composition for oral administration according to any one of the above [4] to [9-12], wherein the zeolite has a cumulative frequency 10% diameter of 5.0 μm or more. [9-14] The composition for oral administration according to any one of the above [4] to [9-13], wherein the zeolite has a cumulative frequency 10% diameter of 5.3 μm or more. [9-15] The composition for oral administration according to any one of the above [4] to [9-13], wherein the crystal shape of the zeolite is coffin-shaped. [9-16] The composition for oral administration according to any one of the above [1] to [9-15], which is a pharmaceutical composition, a supplement, a food product, or a food additive.

[10] The composition for oral administration according to any one of the above [1] to [9-16], which is a pharmaceutical composition.

[11] The composition for oral administration according to the above

[10] , which is used for the prevention, treatment or alleviation of a disease caused by primary, secondary or tertiary amines, ammonia or a metabolite thereof.

[12] The composition for oral administration according to the above-mentioned

[11] , wherein the primary, secondary, or tertiary amine, ammonia, or a metabolite thereof includes one or more selected from the group consisting of trimethylamine, dimethylamine, methylamine, histamine, ammonia, and trimethylamine-N-oxide.

[13] The composition for oral administration according to the above

[12] , wherein the primary, secondary or tertiary amine, ammonia or a metabolite thereof is trimethylamine or trimethylamine-N-oxide.

[14] The composition for oral administration according to any one of the above

[11] to

[13] , wherein the disease caused by a primary, secondary or tertiary amine, ammonia or a metabolite thereof is selected from the group consisting of trimethylaminuria, cardiovascular disease, glaucoma, atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, colorectal cancer, irritable bowel syndrome, hyperammonemia, urea cycle disorders, organic acidemia, hepatic encephalopathy, and portosystemic shunt.

[15] The composition for oral administration according to the above-mentioned

[14] , wherein the disease is a disease caused by trimethylamine, and the disease is trimethylaminuria, a cardiovascular disease, or glaucoma. [15-1] The composition for oral administration according to the above-mentioned

[15] , wherein the disease is a disease caused by trimethylamine, and the disease is trimethylaminuria.

[16] The composition for oral administration according to the above-mentioned

[14] , wherein the disease is a disease caused by trimethylamine-N-oxide, and the disease is atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, or colorectal cancer. [16-1] The composition for oral administration according to the above-mentioned

[16] , wherein the disease is a disease caused by trimethylamine-N-oxide, and the disease is atherosclerosis.

[17] The composition for oral administration according to the above-mentioned

[14] , wherein the disease is a disease caused by histamine, and the disease is irritable bowel syndrome.

[18] The composition for oral administration according to the above-mentioned

[14] , wherein the disease is caused by ammonia, and the disease is hyperammonemia, urea cycle disorder, organic acidemia, hepatic encephalopathy, or portosystemic shunt.

[19] The composition for oral administration according to any one of the above

[10] to

[18] , which contains zeolite as an active ingredient, is administered 1 to 5 times a day, and the dosage of the zeolite is 200 mg to 42,000 mg per administration.

[20] The composition for oral administration described in the above

[19] , wherein the amount of the zeolite administered is 500 mg to 2000 mg per administration.

[21] A method for producing the composition for oral administration according to any one of [4] to

[20] above, comprising obtaining a zeolite by hydrothermal synthesis without using an organic structure-directing agent.

[22] The method according to the above

[21] , wherein sodium carbonate or sodium sulfate is used as a raw material.

[23] The method according to

[21] or

[22] above, which comprises converting the compound into a proton form with an acid.

[24] The method according to

[23] above, wherein the acid is sulfuric acid or nitric acid.

[25] The method according to any one of

[20] to

[24] above, further comprising subjecting the zeolite after hydrothermal synthesis to a surface treatment in a solution containing a Si element source.

[26] Contains zeolite, The zeolite has an MFI structure and is ２ O ３ SiO ２ The molar ratio of is 30.0 or more and 130,000.0 or less, or The zeolite has an FER structure and is ２ O ３ SiO２ The molar ratio of is 15.0 or more and 130,000.0 or less, 1. An oral composition for use in treating, preventing or alleviating symptoms of a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome and hyperammonemia. [26-1] The zeolite has an MFI structure and Al ２ O ３ SiO ２ The molar ratio of is 30.0 or more and 80.0 or less, The zeolite has an FER structure and is ２ O ３ SiO ２ The composition for oral administration described in

[26] above, wherein the molar ratio of is 15.0 or more and 130,000.0 or less.

[27] The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to the above-mentioned

[26] or [26-1], wherein the zeolite has a molar ratio of from 30.0 to 80.0.

[28] The external surface area of ​​the zeolite is 33.0 m ２ The composition for oral administration according to any one of the above

[26] to

[27] , wherein the oral composition has a molecular weight of less than 1000 mg / g. [28-1] The outer surface area of ​​the zeolite is 30.0 m ２ The composition for oral administration according to any one of the above

[26] to

[28] , wherein the oral composition has a molecular weight of less than 1000 mg / g. [28-2] The outer surface area of ​​the zeolite is 26.0 m ２ The composition for oral administration according to any one of the above

[26] to [28-1], wherein the oral composition has a molecular weight of less than 1000 mg / g. [28-3] The outer surface area of ​​the zeolite is 20.0 m ２ The composition for oral administration according to any one of the above

[26] to [28-2], wherein the oral composition is 0.01 to 0.01g / g or less. [28-4] The outer surface area of ​​the zeolite is 15.0 m ２ The composition for oral administration according to any one of the above

[26] to [28-3], wherein the oral composition is 0.01 to 0.01g / g or less. [28-5] The outer surface area of ​​the zeolite is 13.3 m ２The composition for oral administration according to any one of the above

[26] to [28-4], wherein the oral composition is 0.01 to 0.01g / g or less. [28-6] The composition for oral administration according to any one of the above

[26] to [28-5], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1800° or less. [28-7] The composition for oral administration according to any one of the above

[26] to [28-6], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1500° or less. [28-8] The composition for oral administration according to any one of the above

[26] to [28-7], wherein the zeolite has an MFI structure, and the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.0100° or more and 0.1300° or less. [28-9] The composition for oral administration according to any one of the above

[26] to [28-8], wherein the zeolite has a median diameter of 5.5 μm or more. [28-10] The composition for oral administration according to any one of the above

[26] to [28-9], wherein the zeolite has a median diameter of 10.0 μm or more. [28-11] The composition for oral administration according to any one of the above

[26] to [28-10], wherein the zeolite has a median diameter of 11.7 μm or more. [28-12] The composition for oral administration according to any one of the above

[26] to [28-11], wherein the zeolite has a cumulative frequency 10% diameter of 2.5 μm or more. [28-13] The composition for oral administration according to any one of the above

[26] to [28-12], wherein the zeolite has a cumulative frequency 10% diameter of 5.0 μm or more. [28-14] The composition for oral administration according to any one of the above

[26] to [28-13], wherein the zeolite has a cumulative frequency 10% diameter of 5.3 μm or more. [28-15] The composition for oral administration according to any one of the above

[26] to [28-14], wherein the crystal shape of the zeolite is coffin-shaped.

[29] The composition for oral administration according to any one of the above-mentioned

[26] to [28-15], which is a pharmaceutical composition.

[30] The composition for oral administration according to the above-mentioned

[29] , which is administered 1 to 5 times a day, and the dosage of the zeolite is 200 mg to 42,000 mg per administration.

[31] The composition for oral administration according to the above

[30] , wherein the amount of the zeolite administered is 500 mg to 2000 mg per administration.

[32] A method for producing the composition for oral administration according to any one of

[26] to

[31] above, comprising obtaining a zeolite by hydrothermal synthesis without using an organic structure-directing agent.

[33] The method according to the above

[32] , wherein sodium carbonate or sodium sulfate is used as a raw material.

[34] The method according to

[32] or

[33] above, which comprises converting the compound into a proton form with an acid.

[35] The method according to

[34] above, wherein the acid is sulfuric acid or nitric acid.

[36] The method according to any one of

[32] to

[35] above, further comprising subjecting the zeolite after hydrothermal synthesis to a surface treatment in a solution containing a Si element source.

[37] A method for treating or preventing a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia, comprising administering a therapeutically effective amount of an oral composition containing zeolite as an active ingredient to a subject in need of treatment, prevention, or relief of symptoms of the disease, The oral composition is the oral composition according to any one of the above-mentioned

[26] to

[31] . A method for treating, preventing, or alleviating a symptom of a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia.

[38] Use of zeolite for producing an oral composition for treating, preventing, or alleviating a symptom of a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia, comprising: The oral composition is an oral composition according to any one of the above

[26] to

[31] .

[39] An oral composition comprising zeolite for use in treating, preventing, or alleviating symptoms of a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia, comprising: An oral composition, which is the oral composition according to any one of

[26] to

[31] above. According to the present disclosure, by using an inorganic porous material-containing oral composition, it is possible to selectively remove primary, secondary, and tertiary amines or ammonia that act as toxins or pathogenic substances without substantially removing the essential nutrient choline, and the composition is useful for preventing, treating, or alleviating symptoms of diseases caused by primary, secondary, and tertiary amines, ammonia, or their metabolites. FIG. 1 is a histogram showing the distribution of the number of compounds with the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in XRPD for MFI zeolite with a TMA adsorption rate of less than 60% or a choline adsorption rate of more than 40%, and MFI zeolite with a TMA adsorption rate of 60% or more and a choline adsorption rate of 40% or less. FIG. 2 is a graph showing the results of particle size distribution for the zeolites of Example 26, Example 34, Comparative Example 6, and Comparative Example 22. FIG. 3 is a graph showing the time course of the adsorption amount of TMA (top), choline (middle), and arginine (bottom) for Example 26, Example 34, and Comparative Example 6. FIG. 4 is a graph showing the time course of the release amount of choline for Comparative Example 6, Comparative Example 22, Example 26, and Example 34. FIG. 5 is a graph showing the results of particle size distribution for the zeolites of Example 26, Example 34, Comparative Example 6, and Comparative Example 22.

[0010] 6 is a graph showing the energy transition when the process of TMA or choline adsorption in the zeolite layer thickness direction (z-axis direction) of the

[0010] plane and the

[0100] plane is analyzed by first-principles calculation based on density functional theory. FIG. 6-1 shows the cross-sectional structure of the zeolite layer at the energy reference point (z=11 Å), the highest point of the energy barrier (z=7 Å), and internal adsorption (z=0 Å) when the process of TMA adsorption in the zeolite layer thickness direction (z-axis direction) of the

[0010] plane is analyzed by first-principles calculation based on density functional theory. Note that the unit cell of the zeolite is doubled in the horizontal direction of the z axis. FIG. 6-2 shows the cross-sectional structure of the zeolite layer at the energy reference point (z=8 Å), the highest point of the energy barrier (z=5 Å), and internal adsorption (z=0 Å) when the process of choline adsorption in the zeolite layer thickness direction (z-axis direction) of the

[0010] plane is analyzed by first-principles calculation based on density functional theory. The unit cell of zeolite is doubled in the z-axis direction. Figure 6-3 shows the cross-sectional structure of the zeolite layer at the energy reference point (z=9 Å), the highest point of the energy barrier (z=5 Å), and the internal adsorption (z=0 Å) when the process of TMA adsorption in the thickness direction of the zeolite layer (z-axis direction) of the

[0100] plane is analyzed by first-principles calculation based on the density functional theory. The unit cell of zeolite is doubled in the z-axis direction. Figure 6-4 shows the cross-sectional structure of the zeolite layer at the energy reference point (z=9 Å), the highest point of the energy barrier (z=7 Å), and the internal adsorption (z=0 Å) when the process of choline adsorption in the thickness direction of the zeolite layer (z-axis direction) of the

[0100] plane is analyzed by first-principles calculation based on the density functional theory. The unit cell of zeolite is doubled in the z-axis direction. Figure 7 shows the structure of the highest energy barrier (z=5-7 Å) from the viewpoint of the z-axis direction when the process of TMA or choline adsorption in the thickness direction (z-axis direction) of the zeolite layer of the

[0010] plane is analyzed by first-principles calculation based on the density functional theory. Note that the unit cell of the zeolite is doubled in the z-axis direction.FIG. 8 is a graph showing the plasma concentration time course of d9-TMA (top) and its AUC (bottom) when fasting choline-loaded mice were administered multiple doses of the zeolite of Example 34. The results are shown as mean ± standard error, and † indicates a significant difference from the vehicle group (Shirley-Williams test, P < 0.05). FIG. 9 is a graph showing the plasma concentration time course of d9-choline (top) and d9-TMA (bottom) when fasting choline-loaded mice were administered multiple doses of the zeolite of Comparative Example 6. The results are shown as mean ± standard error. FIG. 10 is a diagram showing the XRPD patterns of Example 34 (top) and Example 52 (bottom). FIG. 11 is a conceptual diagram of a physiologically based pharmacokinetics (PBPK) model for d9-choline, d9-TMA, and d9-TMAO when d9-choline was orally administered to mice. Figure 12-1 is a graph showing a comparison of the individual measured values ​​(dashed lines) and the PBPK model predicted values ​​(solid lines) of the plasma concentrations of d9-choline (top), d9-TMA (center), and d9-TMAO (bottom) over time in the vehicle group of fasted choline-loaded mice. Figure 12-2 is a graph showing a comparison of the individual measured values ​​(dashed lines) and the PBPK model predicted values ​​(solid lines) of the plasma concentrations of d9-choline (top), d9-TMA (center), and d9-TMAO (bottom) over time in fasted choline-loaded mice administered the zeolite of Example 34 at a dose of 500 mg / kg. Fig. 12-3 is a graph showing a comparison between the individual measured values ​​(dashed lines) and the predicted values ​​(solid lines) by the PBPK model for the plasma concentration time course of d9-choline (top), d9-TMA (center), and d9-TMAO (bottom) when the zeolite of Example 34 was administered at a dose of 1000 mg / kg to fasted choline-loaded mice. Fig. 12-4 is a graph showing a comparison between the individual measured values ​​(dashed lines) and the predicted values ​​(solid lines) by the PBPK model for the plasma concentration time course of d9-choline (top), d9-TMA (center), and d9-TMAO (bottom) when the zeolite of Example 34 was administered at a dose of 2000 mg / kg to fasted choline-loaded mice.FIG. 13 is a graph showing the urinary excretion of d9-TMA and TMAO (top), native TMA and TMAO (middle), and d9-TMA, d9-TMAO, native TMA and native TMAO (bottom) when the zeolite of Example 34 was administered in large doses to choline-loaded mice under feeding. The results are shown as mean ± standard error, and # indicates significant difference from the vehicle group (Williams multiple comparison test, #: P < 0.025, ##: P < 0.005, ###: P < 0.0005). The graph also includes the urinary excretion when the zeolite of Example 70 was administered at a dose of 1000 mg / kg. The results are shown as mean ± standard error, and * indicates significant difference from the vehicle group (Student's t test, *: P < 0.05, **: P < 0.01). The present disclosure will be described in detail below. The oral composition of the present disclosure comprises: Contains an inorganic porous material, When 11.8 g of the inorganic porous material per 1 mmol of choline is mixed with a mixture of equimolar amounts of choline and primary, secondary, and tertiary amines or ammonia in artificial intestinal juice at a concentration of 2 g / L for 1 hour, the adsorption rate of the primary, secondary, and tertiary amines or ammonia is 60.0% or more, and the adsorption rate of choline is 40.0% or less. <Inorganic porous body> The inorganic porous body is an inorganic material having a plurality of pores therein, and preferably means an inorganic material having a large number of fine pores with a pore diameter of 100 μm or less therein. The inorganic material is preferably a silicate, which is a compound containing at least silicon (Si) and oxygen (O), and in which some of these atoms may be substituted with other atoms. For example, the silicate may be an aluminosilicate in which some silicon atoms are substituted with aluminum atoms. That is, the inorganic material is preferably a silicate or an aluminosilicate. An aluminosilicate is a compound containing at least aluminum (Al), silicon (Si), and oxygen (O), and some of these atoms may be substituted with other atoms. The aluminosilicate in the present disclosure is a compound containing isotopes (e.g., ２ H. ３ H. １７ O. １８ O. ２９ Si, ３０ The present invention includes compounds labeled with fluorine, such as fluorine-1, fluorine-2, fluorine-3, fluorine-4, fluorine-5, fluorine-6, fluorine-7, fluorine-8, fluorine-9, fluorine-11, fluorine-12, fluorine-13, fluorine-14, fluorine-15, fluorine-16, fluorine-17, fluorine-17, fluorine- Examples of the aluminosilicate include zeolite, mullite, kaolinite, and illite, with zeolite being preferred. As the zeolite, any zeolite defined by the International Zeolite Association (IZA) can be used. Zeolite Al ２ O ３ SiO ２ That is, the molar ratio of SiO ２ / Al ２ O ３ The ratio is usually 15.0 or more, preferably 18.0 or more, more preferably 20.0 or more, even more preferably 30.0 or more, and particularly preferably 31.0 or more. On the other hand, it is usually 130,000.0 or less, preferably 129,000.0 or less, more preferably 50,000.0 or less, even more preferably 10,000.0 or less, even more preferably 1,000.0 or less, still more preferably 500.0 or less, particularly preferably 100.0 or less, and particularly preferably 80.0 or less. Such a specific range of SiO ２ / Al ２ O ３ By using a molar ratio of zeolite, the polarity of the zeolite can be controlled within a certain range, and high selectivity of adsorption for primary, secondary, and tertiary amines or ammonia can be maintained relative to choline. In addition, SiO ２ / Al ２ O ３ The ratio is the molar ratio of the amounts of Si and Al contained in the zeolite, expressed as SiO ２ , Al ２ O ３When converted to molar amount of Al ２ O ３ SiO ２ The method for measuring the content of each component is not particularly limited, but examples thereof include composition analysis using ICP (inductively coupled plasma analysis) and XRF (X-ray fluorescence analysis). In addition, SiO of zeolite ２ / Al ２ O ３ The ratio can be adjusted by the reaction conditions for zeolite synthesis, etc. The structure of zeolite can be expressed by the codes specified by IZA, for example, ABW, ACO, AEI, AEN, AFI, AFT, AFX, ANA, ATN, ATT, ATV, AWO, AWW, BIK, CHA, DDR, DFT, EAB, EPI, ERI, ESV, GIS, GOO, ITE, JBW, KFI, LEV, LTA, MER, MON, MTF, OWE, P AU, PHI, RHO, RTE, RWR, SAS, SAT, SAV, SIV, TSC, UFI, VNI, YUG, AEL, AFO, AHT, DAC, FER, HEU, IMF, IT Examples include H, MEL, MFS, MWW, OBW, RRO, SFG, STI, SZR, TER, TON, TUN, WEI, MFI, MON, PAU, PHI, MOR, FAU, and the like. The structure of a zeolite is a crystal structure of crystals formed by tetrahedra, in which four oxygen atoms are coordinated to a cation, linked together while sharing the apex oxygen with adjacent cations. For substances whose crystal structures have been clarified, a structure code is defined by IZA for each framework topology, and the type of structure is expressed using this notation. It is particularly preferable that the zeolite contains a zeolite having a pore structure with a maximum number of rings of 10. This makes it possible to control the pore size and increase the adsorption selectivity for primary, secondary, and tertiary amines or ammonia compared to choline. The number of rings refers to the number of oxygen atoms contained in the ring structure constituting the cross section of the zeolite pores, and the maximum number of rings refers to the pore with the largest number of oxygen atoms among the pores composed of oxygen and T elements (elements other than oxygen constituting the zeolite framework) that form the zeolite framework. For example, when pores with 10-membered oxygen rings and 8-membered oxygen rings exist as in FER-type zeolite, the zeolite is considered to be a zeolite with 10-membered oxygen rings. The maximum spherical diameter of diffusion in the zeolite pores is preferably 3.68 Å or more, more preferably 3.70 Å or more, even more preferably 3.75 Å or more, even more preferably 4.22 Å or more, even more preferably 4.50 Å or more, particularly preferably 4.65 Å or more, and most preferably 4.69 Å or more. On the other hand, the upper limit of the maximum spherical diameter of diffusion in the pores is preferably 4.91 Å or less, more preferably 4.90 Å or less, even more preferably 4.85 Å or less, even more preferably 4.80 Å or less, even more preferably 4.75 Å or less, particularly preferably 4.73 Å or less, and most preferably 4.71 Å or less. By having the maximum spherical diameter of diffusion within the pores within the above range, it is possible to further increase the adsorption selectivity for primary, secondary, and tertiary amines, or ammonia, compared with choline. The maximum sphere diameter (Å) of diffusion in the pores can be found in the Maximum diameter of a sphere that can diffuse along each framework code page of the Zeolite Framework Types (https: / / asia.iza-structure.org / IZA-SC / ftc_table.php) of the Structure Commission of the International Zeolite Association (IZA-SC). When there are multiple values ​​for the a, b, and c axes, the largest one is referred to. Examples of zeolites having a pore structure with a maximum number of rings of 10 include AEL, AFO, AHT, CGF, CGS, DAC, EUO, FER, HEU, IMF, ITH, LAU, MEL, MFI, MFS, MTT, MWW, NES, OBW, PON, RRO, SFF, SFG, STF, STI, SZR, TER, TON, TUN, and WEI. Among them, zeolites having a pore structure with a maximum number of rings of 10 and a maximum spherical diameter of diffusion in the pores of 3.68 Å or more are preferred. As such zeolites, FER or MFI is preferred, and MFI is more preferred. The counter cation of zeolite is H ＋ (proton), NH ４ ＋ , alkali metal ions (Li ＋ , Na ＋ , K ＋ , Rb ＋ , Cs ＋ etc.), Group 2 element ions (Ca ２＋ , Mg ２＋ , Sr ２＋ , Ba ２＋ etc.), transition metal ions (Fe ２＋ , Cu ２＋ , Zn ２＋ Among these, proton, NH ４ ＋ , Li ＋ , Na ＋ , K ＋ As an ion suitable for oral administration, a proton is preferable because it can be used safely in living organisms and prevents excessive intake of various ions. Zeolite has an external surface area of ​​33.0 m ２ It is preferable to use one having a molecular weight of less than 30.0 m / g. ２ / g, and even more preferably less than 26.0 m ２ / g, more preferably less than 25.8 m ２ / g, even more preferably less than 25.6 m ２ / g or less, particularly preferably 20.0m ２ / g or less, and particularly preferably 15.0m ２ / g or less, and most preferably 13.3m２ The lower limit is not particularly limited, but is, for example, 0.1 m ２ / g or more, 1.0m ２ / g or more, 3.0m ２ / g or more, 5.0m ２ / g or more, 6.5m ２ / g or more. By setting the external surface area within a certain range, it is possible to obtain better selectivity for adsorption of primary, secondary, and tertiary amines or ammonia compared to choline. Here, the external surface area refers to the total surface area per unit mass of the solid minus the internal surface area of ​​the pores per unit mass. This value can be calculated from the slope and intercept of the plateau portion in a t-plot (standard isotherm: de-Bore equation) obtained by measuring the nitrogen adsorption isotherm at liquid nitrogen temperature for a powder that has been subjected to heating and degassing as a pretreatment. In addition, it is preferable to use an MFI zeolite in which the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation is 0.1800° or less. It is more preferably 0.1500° or less, and even more preferably 0.1300° or less. There is no particular lower limit, but it is, for example, 0.0100° or more, 0.0300° or more, 0.0500° or more, 0.0700° or more, or 0.0900° or more. By setting the half-width of the maximum peak present in the range of 2θ=7.9000°±0.5000° in a powder X-ray diffraction pattern measured with Cu-Kα radiation to a certain range, it is possible to improve the selectivity of adsorption for primary, secondary, and tertiary amines or ammonia compared to choline. Here, the half-width refers to the spectral width at half the value of the peak maximum value. The zeolite used has a median diameter of particle size distribution of preferably 5.5 μm or more, more preferably 10.0 μm or more, and even more preferably 11.7 μm or more. There is no particular upper limit, but it is, for example, 10.0 mm or less. By setting the median diameter of the particle size distribution within a certain range, it is possible to improve the selectivity of adsorption for primary, secondary, and tertiary amines or ammonia compared to choline. In addition, it is preferable to use zeolite having a cumulative frequency 10% diameter of particle size distribution of 2.5 μm or more, more preferably 5.0 μm or more, and further preferably 5.3 μm or more. There is no particular upper limit, but it is, for example, 5.0 mm or less. By setting the cumulative frequency 10% diameter of the particle size distribution within a certain range, it is possible to improve the selectivity of adsorption for primary, secondary, and tertiary amines or ammonia compared to choline. Here, the median diameter and 10% cumulative frequency diameter in the particle size distribution are particle sizes at which the integrated values ​​in the particle size distribution obtained by a laser diffraction / scattering method are 50% and 10%, respectively, and are values ​​measured using pure water as a dispersion medium, applying ultrasonic waves, and circulating the particles in a flow cell. Moreover, the crystal shape of the MFI zeolite is preferably a coffin type. By making the crystal shape of the MFI zeolite a certain shape, it is possible to improve the adsorption selectivity for primary, secondary, and tertiary amines or ammonia compared to choline. Here, the coffin shape refers to a shape in which the

[010] plane is dominant when observed with a scanning electron microscope (SEM). Furthermore, by selectively treating the surfaces of the surfaces other than the

[010] surface, it is possible to improve the selectivity of adsorption of primary, secondary, and tertiary amines or ammonia compared to choline. The zeolite may be purchased from the market and used, or may be synthesized by hydrothermal synthesis or the like as described below. In the oral composition of the present disclosure, when choline and primary, secondary, tertiary amine, or ammonia present as a mixture in equimolar amounts in artificial intestinal fluid are mixed with 11.8 g of the inorganic porous material per 1 mmol of choline at a concentration of 2 g / L for 1 hour, the adsorption rate of primary, secondary, tertiary amine, or ammonia is 60.0% or more, and the adsorption rate of choline is 40.0% or less. The adsorption rate of primary, secondary, and tertiary amines or ammonia is usually 60.0% or more, preferably 60.4%, more preferably 70.0% or more, even more preferably 80.0%, and particularly preferably 90.0% or more. On the other hand, the adsorption rate of primary, secondary, and tertiary amines or ammonia can be, for example, 100.0% or less. The choline adsorption rate is usually 40.0% or less, preferably 30.0% or less, more preferably 20.0% or less, and even more preferably 10.0% or less. On the other hand, the choline adsorption rate can be, for example, 0.0% or more, 0.1% or more, or 0.2% or more. In addition, the adsorption rate of the primary, secondary, or tertiary amine or ammonia is preferably 2.00 times or more, more preferably 2.49 times or more, and even more preferably 2.50 times or more, the adsorption rate of the choline. On the other hand, although there is no particular upper limit, the adsorption rate of the primary, secondary, or tertiary amine or ammonia can be, for example, 350.00 times or less, 342.00 times or less, or 341.70 times or less, the adsorption rate of the choline. Here, choline is a compound identified by CAS Registry Number 62-49-7 (CH ３ ) ３ N ＋ (CH ２ ) ２ It is a quaternary ammonium cation with the rational formula OH. Ammonia is a compound identified by the CAS registry number 7664-41-7, NH ３ The ammonium cation (NH ４ ＋ ) is also included. Primary, secondary, and tertiary amines are compounds in which the hydrogen atom of ammonia is replaced with a hydrocarbon group or an aromatic atomic group. If the number of substitutions is one, it is called a primary amine, if the number of substitutions is two, it is called a secondary amine, and if the number of substitutions is three, it is called a tertiary amine. For example, heterocyclic aromatic compounds such as imidazole and pyridine are also included in the amines. Primary, secondary, and tertiary amines also include their conjugate acids. As the artificial intestinal fluid, fasting-state simulated small intestinal fluid (FaSSIF) is used. Reference: Dissolution Technologies 20(3):44-50 "Comparison of the Solubility and Dissolution of Drugs in Fasted-State Biorelevant Media (FaSSIF and FaSSIF-V2)" Specifically, FaSSIF (pH 6.5) having the following composition can be used. 3.5 mM sodium taurocholate, 0.75 mM lecithin, 105.85 mM sodium chloride, 10.5 mM sodium hydroxide, 28.65 mM sodium dihydrogen phosphate. The adsorption rate means a value obtained by dividing the concentration of a substance adsorbed to the adsorbent in a solution after the adsorption operation by the concentration of the substance in the solution before the adsorption operation and subtracting the result from 1. For example, by placing equal molar amounts of choline and primary, secondary, and tertiary amines or ammonia in an artificial intestinal fluid, and adding an inorganic porous material equivalent to 11.8 g per 1 mmol of choline at a concentration of 2 g / L, and allowing the adsorption reaction to occur at room temperature for 1 hour, the adsorption rates of choline and primary, secondary, and tertiary amines or ammonia are measured, and it can be confirmed that the adsorption rate of primary, secondary, and tertiary amines or ammonia is 60.0% or more and that the adsorption rate of choline is 40.0% or less. Room temperature is a temperature of 20°C ± 10°C. In addition, for example, by placing equal molar amounts of choline and TMA in artificial intestinal juice, and adding the inorganic porous material at a concentration of 2 g / L in an amount equivalent to 11.8 g per 1 mmol of choline, and allowing the adsorption reaction to occur for 1 hour, the adsorption rates of choline and TMA are measured, and it can be confirmed that the adsorption rate of TMA is 60.0% or more and the adsorption rate of choline is 40.0% or less. <Oral Composition> The oral composition refers to a mixture of substances suitable for oral administration to an individual. For example, the oral composition may include one or more inorganic porous bodies and orally acceptable carriers (excipients, binders, disintegrants, flavorings, odorants, emulsifiers, diluents, solubilizing agents, etc.). Carriers acceptable for oral administration are appropriately selected depending on the dosage form, and examples thereof include excipients, lubricants, binders and disintegrants in solid preparations, and solvents, solubilizers, emulsifiers, diluents, suspending agents, isotonicity agents, buffers and soothing agents in liquid preparations. Furthermore, additives such as conventional preservatives, antioxidants, colorants, flavorings, odorants and wetting agents can be used appropriately and in appropriate amounts, if necessary. The dosage form of the oral composition may be a solid or liquid dosage form, specifically, tablets, coated tablets, pills, fine granules, granules, powders, capsules, syrups, emulsions, suspensions, injections, troches, enteric capsules, etc. The oral composition of the present disclosure may further contain other therapeutically effective drugs, for example, inhibitors of TMA-producing enzymes such as cutC and cntAB, TMA-degrading enzymes such as trimethylamine dehydrogenase, riboflavin, and antibacterial agents. In addition, ingredients such as anti-inflammatory agents, vitamins, and amino acids can also be added as necessary. An oral composition containing the inorganic porous material of the present disclosure can be used, for example, as a pharmaceutical composition, a supplement, a food, or a food additive. The supplements, foods, and food additives may be supplements, foods, and food additives that are indicated with a function or use such as for adsorbing primary, secondary, or tertiary amines or ammonia, for adsorbing and removing primary, secondary, or tertiary amines or ammonia, or for preventing, treating, or alleviating symptoms of diseases caused by primary, secondary, or tertiary amines, ammonia, or metabolites thereof. The oral composition containing the inorganic porous material of the present disclosure can be preferably used as a pharmaceutical composition, specifically, can be used for treating, preventing, or alleviating symptoms of diseases caused by primary, secondary, or tertiary amines, ammonia, or metabolites thereof. The inorganic porous material contained in the oral composition of the present disclosure is insoluble in water and has a particle size (100 nm) that is suitable for endocytosis, so that its absorption into the body is negligible. In addition, the zeolite contained in the oral composition of the present disclosure is stable in the stomach and other digestive tracts, and the elution of the components containing silicon and aluminum is very small, so that the safety of taking the composition is high. One embodiment of the present disclosure is a pharmaceutical composition for treating, preventing, or alleviating symptoms of a disease caused by a primary, secondary, or tertiary amine, ammonia, or a metabolite thereof, comprising an inorganic porous body according to the above-described embodiment of the present disclosure or an oral composition containing the same. One embodiment of the present disclosure is a method for treating, preventing, or alleviating symptoms of a disease caused by a primary, secondary, or tertiary amine, ammonia, or a metabolite thereof, comprising a step of administering to a subject an effective amount of an inorganic porous body according to the above-described embodiment of the present disclosure or an oral composition containing the same. One embodiment of the present disclosure is use of the inorganic porous body according to the above embodiment of the present disclosure or an oral composition containing the same for producing a medicament for treating, preventing, or alleviating symptoms of a disease caused by a primary, secondary, or tertiary amine, ammonia, or a metabolite thereof. One embodiment of the present disclosure is an inorganic porous material according to the above-described embodiment of the present disclosure or an oral composition containing the same, for treating, preventing, or alleviating symptoms of a disease caused by a primary, secondary, or tertiary amine, ammonia, or a metabolite thereof. The primary, secondary, and tertiary amines, ammonia, or metabolites thereof are preferably one or more selected from the group consisting of trimethylamine, dimethylamine, methylamine, histamine, ammonia, and trimethylamine-N-oxide, and more preferably trimethylamine or trimethylamine-N-oxide. Diseases caused by primary, secondary, and tertiary amines, ammonia, or metabolites thereof are not particularly limited as long as they are diseases or symptoms that can be caused by these substances, and examples of such diseases include diseases that can be treated, prevented, or alleviated by reducing or removing these substances. More specifically, diseases caused by primary, secondary, and tertiary amine ammonia or metabolites thereof include trimethylaminuria, cardiovascular disease, glaucoma, atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, colorectal cancer, irritable bowel syndrome, hyperammonemia, urea cycle disorders, organic acidemia, hepatic encephalopathy, and portosystemic shunt. For example, when the causative substance of a disease is trimethylamine, the disease that can be treated, prevented, or alleviated by an oral composition containing the inorganic porous material of the present disclosure can be trimethylaminuria, cardiovascular disease, or glaucoma, preferably trimethylaminuria. Here, trimethylaminuria is a disease in which trimethylamine generated during digestion and decomposition of ingested food in the body is not metabolized and is excreted in sweat, urine, and breath. It is also called fish odor syndrome because trimethylamine smells like rotten fish. It is roughly divided into type 1 (primary trimethylaminuria) in which flavin-containing monooxygenase 3 (FMO3), an enzyme that oxidizes trimethylamine, is congenitally absent or low in activity as genetic information, and type 2 (secondary trimethylaminuria) in which it is acquired due to renal and hepatic dysfunction, renal and hepatic dysfunction, portosystemic shunt, intestinal flora imbalance (dysbiosis), or excessive intake of trimethylamine precursors or a combination of these factors. In addition, there are intermittent forms in which FMO3 expression increases and decreases in correlation with the menstrual cycle due to the influence of steroid hormones, and transient forms in which FMO3 expression is reduced in infants and children. Different forms may also be mixed together. The relationship between trimethylamine and various diseases is described in, for example, the following literature: Trimethylaminuria: European Journal of Human Genetics volume 23, page1269 (2015) Cardiovascular disease: Toxins 2019, 11(9), 490 Glaucoma: International Ophthalmology volume 41, pages 341-347 (2021) For example, when the causative substance of a disease is trimethylamine-N-oxide, the disease that can be treated, prevented, or alleviated by an oral composition containing the inorganic porous material of the present disclosure can be atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, or colorectal cancer, preferably atherosclerosis. Atherosclerosis is a disease in which patchy intimal plaques (atheromas) grow into the lumen of medium and large arteries, thereby reducing or blocking blood flow. The relationship between trimethylamine-N-oxide and various diseases is described in, for example, the following documents: Atherosclerosis: Nature Medicine volume 19, pages 576-585 (2013) Coronary heart disease: BMC Cardiovascular Disorders (2020) 20:7 Preserved ejection fraction heart failure: BMC Cardiovascular Disorders (2020) 20:394 ST-segment elevation myocardial infarction: American Journal of Cardiology. 2019 Mar 15;123(6):894-898.Abdominal aortic aneurysm: Circulation Volume 147, Issue 14, 4 April 2023; Pages 1079-1096 Atrial fibrillation: International Journal of Cardiology Volume 267, 15 September 2018, Pages 100-106 Ischemic stroke: Journal of Biochemistry and Molecular Toxicology 2019 Feb;33(2):e22246 Post-stroke cognitive impairment: Neurological Sciences volume 41, pages 57-63 (2020) Mild cognitive impairment and Alzheimer's disease: Alzheimer's Research & Therapy (2018) 10:124 Obesity Reviews. 2020;21(5):e12993. Advanced chronic kidney disease with type 2 diabetes: Journal of Clinical Medicine 2017, 6(9), 86 Cardiovascular complications in chronic kidney disease: Kidney International Volume 92, Issue 4, October 2017, Pages 809-815 Diabetic retinopathy: Acta Diabetologica 58, 221-229 (2021) Nonalcoholic fatty liver disease: Diabetes & Metabolism 47 (2021) 101183 Polycystic ovary syndrome: BMC Endocr Disord. 2020; 20: 3. Parkinson's Disease: Clinica Chimica Acta Volume 501, February 2020, Pages 165-173 Colorectal cancer: International Journal of Molecular Sciences 2020, 21, 6782 For example, when the causative substance of a disease is histamine, the disease that can be treated, prevented, or alleviated by an oral composition containing the inorganic porous material of the present disclosure can be irritable bowel syndrome. Here, irritable bowel syndrome refers to a syndrome in which abnormal bowel movements such as chronic diarrhea or constipation, abdominal pain, and abdominal distension occur despite the absence of organic abnormalities such as ulcers or tumors in the large or small intestine. The relationship between histamine and irritable bowel syndrome is described, for example, in the following literature: Science Translational Medicine 14, eabj1895 (2022) For example, when the causative substance of a disease is ammonia, the disease that can be treated, prevented, or alleviated by an oral composition containing the inorganic porous material of the present disclosure can be hyperammonemia, urea cycle disorder, organic acidemia, hepatic encephalopathy, or portosystemic shunt, and is preferably hyperammonemia. Here, hyperammonemia is a disease in which the body cannot metabolize ammonia and ammonia accumulates in the blood. Causes include liver cirrhosis, fulminant hepatitis, impaired function of the urea cycle due to liver dysfunction, portosystemic shunt, urea cycle disorder, organic acidemia, ammonia production associated with infection with urease-producing bacteria, and drug-induced (sodium valproate, pivalic acid-containing antibiotics). Hyperammonemia can also lead to symptoms such as hepatic encephalopathy and hepatic coma. The relationship between ammonia and hyperammonemia and its associated diseases is described in the following documents: Pediatric Nephrology volume 27, pages207-222 (2012) In addition, the inventors have found that zeolite, particularly Al, is a porous inorganic material. ２ O ３ SiO ２ and zeolites having a maximum ring number of 10 and a maximum intrapore diffusion spherical diameter of 3.68 Å or more, have excellent performance in selectively adsorbing primary, secondary, and tertiary amines or ammonia compared to choline, and are useful for treating, preventing, or alleviating symptoms of diseases caused by primary, secondary, and tertiary amines, ammonia, or metabolites thereof. Based on the above findings, one embodiment of the oral composition of the present disclosure is: Contains zeolite, The zeolite has an MFI structure and is ２ O ３ SiO ２ The molar ratio of is 30.0 or more and 130,000.0 or less, or The zeolite has an FER structure and is ２ O ３ SiO ２ The molar ratio of is 15.0 or more and 130,000.0 or less, and an oral composition for use in the treatment, prevention, or alleviation of symptoms of one or more diseases selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia. Alternatively, a preferred embodiment of the oral composition of the present disclosure is Contains zeolite, The zeolite has an MFI structure and is ２ O ３ SiO ２ or The zeolite has an FER structure and is ２ O ３ SiO ２ The molar ratio of is 15.0 or more and 130,000.0 or less, and an oral composition for use in the treatment, prevention, or alleviation of symptoms of one or more diseases selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome, and hyperammonemia. The oral composition or pharmaceutical composition containing the inorganic porous material of the present disclosure can be administered to a subject by oral administration. The "subject" to which the oral composition or pharmaceutical composition of the present disclosure is administered includes humans and non-human mammals (e.g., one or more of mice, guinea pigs, hamsters, rats, mice, rabbits, pigs, sheep, goats, cows, horses, cats, dogs, marmosets, monkeys, chimpanzees, etc.). The "subject" may be a patient diagnosed with a disease caused by primary, secondary, or tertiary amines, ammonia, or metabolites thereof, or a subject at risk of developing a disease caused by primary, secondary, or tertiary amines, ammonia, or metabolites thereof. "Treatment" includes any treatment of a disease in a mammal, particularly a human, and includes inhibiting the symptoms of the disease, i.e., arresting its progression or eliminating the disease or condition, causing regression of the disease or condition, or slowing the progression of the condition. "Relief of symptoms" includes reducing or alleviating the symptoms of the disease and reducing the frequency of symptoms in a mammal, particularly a human. "Prophylaxis" includes preventing the onset of the above-mentioned diseases in mammals, particularly humans. The dosage of the oral composition or pharmaceutical composition containing the inorganic porous material of the present disclosure is determined by a doctor based on various factors, such as the type of disease, the severity of symptoms, the age, sex, and weight of the patient, the severity of the disease, pharmacological findings such as pharmacokinetics and toxicological characteristics, the presence or absence of a drug delivery system, and whether the composition is administered as part of a combination of other drugs. Orally administered, for an adult (body weight 60 kg), the dosage can usually be 200 mg / dose to 42,000 mg / dose, preferably 500 mg / dose to 2,000 mg / dose. The dosage can be one or more times per day, for example, 1 to 5 times per day. <Method of manufacturing zeolite> One aspect of the present disclosure relates to a method for producing zeolite. However, the zeolite contained in the oral composition of the present disclosure is not limited to those obtained by the following production method. Hydrothermal synthesis is a method of synthesis and crystal growth of substances that is carried out in the presence of high-temperature water of 50° C. or higher. In the method for producing zeolite, hydrothermal synthesis is carried out in a reaction system containing a Si element source (a substance containing at least silicon (Si)), an Al element source (a substance containing at least aluminum (Al)), an alkali metal salt, and water, and further containing a structure directing agent as necessary. Zeolite seed crystals may be added to the reaction system. As the Al element source, aluminum sulfate, aluminum nitrate, aluminum hydroxide, sodium aluminate, pseudoboehmite, alumina sol, aluminum alkoxides such as aluminum isopropoxide, etc. may be used. Furthermore, aluminum-containing zeolites such as FAU-type zeolite (e.g., Y-type zeolite) and CHA-type zeolite may be used as the aluminum source. Among these aluminum sources, aluminum sulfate, aluminum nitrate, aluminum hydroxide, or aluminum-containing zeolites are preferred in terms of reactivity, and aluminum hydroxide or aluminum-containing zeolites are more preferred. The amount of the Al element source used is, in terms of ease of preparation of the pre-reaction mixture or the aqueous gel obtained by aging the pre-reaction mixture and production efficiency, usually 0.001 or more, preferably 0.005 or more, more preferably 0.01 or more, and even more preferably 0.02 or more, in terms of the molar ratio of aluminum (Al) in the Al element source to silicon (Si) contained in the raw material mixture other than the seed crystals added as necessary. The upper limit is not particularly limited, but is usually 1 or less, preferably 0.5 or less, more preferably 0.25 or less, even more preferably 0.1 or less, particularly preferably 0.08 or less, and most preferably 0.06 or less, in terms of uniformly dissolving the Al element source in the aqueous gel. The Si element source is not particularly limited, and various known substances can be used, such as colloidal silica, amorphous silica, sodium silicate, trimethylethoxysilane, tetraethylorthosilicate, aluminosilicate gel, and zeolite containing Si atoms. These may be used alone or in combination of two or more. Among these, raw materials that can be mixed sufficiently uniformly with other components and are particularly easily dissolved in water are preferred, and colloidal silica, trimethylethoxysilane, tetraethylorthosilicate, or aluminosilicate gel are preferred. The alkali metal cation exists in the vicinity of the aluminum anion to perform charge compensation, and has the effect of assisting the crystal growth of the desired structure, similar to the structure-directing agent. The alkali metal salt includes a sodium salt and / or a potassium salt, and may also include other alkali metal atoms. The other alkali metal atoms are not particularly limited and may be any known alkali metal atom used in zeolite synthesis, such as lithium, rubidium, and cesium, and may be used in combination of two or more of them. As the alkali metal salt, inorganic acid salts such as hydroxides, oxides, carbonates, sulfates, nitrates, phosphates, chlorides, bromides, etc., and organic acid salts such as acetates, oxalates, citrates, etc., of the above-mentioned alkali metal atoms can be used. One type or two or more types of alkali metal salts may be contained. From the viewpoint of facilitating crystal formation, the amount of water used is usually 5 or more, preferably 10 or more, more preferably 12 or more, even more preferably 15 or more, and particularly preferably 17 or more, in terms of the molar ratio to silicon (Si) contained in the raw material mixture other than the seed crystals. This range is preferable because it makes crystal formation easier. In addition, in order to fully obtain the effect of reducing the cost of waste liquid treatment, the molar ratio to silicon (Si) contained in the raw material mixture other than the seed crystals is usually 100 or less, preferably 90 or less, more preferably 75 or less, and even more preferably 50 or less. The structure-directing agent is a substance that may be added as a raw material during the synthesis of zeolite, and is a material added to control the structure of the zeolite obtained by synthesis. The type of the structure-directing agent is not limited as long as it can synthesize the desired zeolite. In addition, the structure-directing agent may be used alone or in combination of two or more types, or these structure-directing agents may not be used. Structure-directing agents are broadly classified into organic structure-directing agents and inorganic structure-directing agents. Organic structure-directing agents typically include amines, quaternary ammonium salts, primary alcohols, etc. Inorganic structure-directing agents include nitrates, sulfates, carbonates, etc., which have inorganic ions as cations. When used as an organic structure-directing agent, a calcination process is required to remove the structure-directing agent from the zeolite, but there are no approved pharmaceuticals that require a calcination process, and it is believed that there are no calcination facilities that comply with GMP for pharmaceutical manufacturing. Therefore, in order to use the oral composition of the present disclosure for pharmaceutical purposes, it is preferable not to use an organic structure-directing agent in the hydrothermal synthesis. That is, in a preferred embodiment, the method for producing the oral pharmaceutical composition of the present disclosure is a method that includes obtaining zeolite by hydrothermal synthesis without using an organic structure-directing agent. In addition, from the viewpoint of obtaining zeolite of good quality, it is more preferable to use an inorganic structure-directing agent in the hydrothermal synthesis. Furthermore, when the target zeolite is an MFI type, it is preferable to use an inorganic salt with Na as the cation as the inorganic structure-directing agent in terms of ease of synthesizing MFI type zeolite, and it is even more preferable to use sodium carbonate or sodium sulfate in terms of a large effect of increasing the particle size. In the method for producing zeolite, a Si element source, an Al element source, an alkali metal salt, and water, and optionally a structure-directing agent are mixed together to obtain a mixture, and if necessary, seed crystals are further added to the mixture, and the obtained pre-reaction mixture is subjected to hydrothermal synthesis. The order of mixing these raw materials is not particularly limited. However, it is preferable to prepare an alkaline solution by mixing water and an alkali metal salt, and then add the Al element source, Si element source, and if necessary, seed crystals to the alkaline solution in this order, in order from the viewpoint of dissolving the raw materials more uniformly when the Si element source and the Al element source are added after the alkaline solution is prepared. Zeolite is usually used as the seed crystals. If the zeolite to be produced is an aluminosilicate, the seed crystals are preferably zeolite of the same aluminosilicate. The seed crystals may contain an amorphous component as a part thereof. The zeolite used as the seed crystals may or may not contain an organic structure directing agent. The method for producing the zeolite to be used as the seed crystals is not particularly limited, and may be produced by the zeolite production method exemplified as the production method of the oral composition of the present disclosure, or may be produced by other methods, such as a general batch method using an autoclave. The amount of the seed crystals is preferably large in terms of the effect of promoting crystallization as the seed crystals being easily manifested. On the other hand, it is preferable that the amount of the seed crystals is small in terms of the ease of dissolving the seed crystals and the ease of functioning as the seed crystals. Therefore, the silica (SiO ２ ), it is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and even more preferably 1.0% by mass or more. On the other hand, it is preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, and particularly preferably 10% by mass or less. In addition to the above-mentioned Al element source, Si element source, alkali metal salt, water, and seed crystals as needed, other additives such as auxiliary agents that serve as components for assisting the synthesis of zeolite, for example, acid components that promote the reaction, and metal stabilizers such as polyamines, may be added and mixed in any step as needed to prepare a pre-reaction mixture. The pre-reaction mixture prepared as described above may be hydrothermally synthesized immediately after preparation, but in order to obtain a zeolite having high crystallinity, it is preferable to age it for a certain period of time under a predetermined temperature condition. In particular, when scaling up, the stirring property is deteriorated and the raw material is likely to be insufficiently mixed. Therefore, it is preferable to improve the raw material to a more uniform state by aging the raw material while stirring it for a certain period of time. The aging temperature is usually 100° C. or less, preferably 95° C. or less, more preferably 90° C. or less, and although there is no particular lower limit, it is usually 0° C. or more, preferably 10° C. or more. The aging temperature may be constant during aging, or may be changed stepwise or continuously. The aging time is not particularly limited, but is usually 2 hours or more, preferably 3 hours or more, more preferably 5 hours or more, and is usually 30 days or less, preferably 10 days or less, and more preferably 4 days or less. Hydrothermal synthesis is carried out, for example, by placing the pre-reaction mixture prepared as described above or an aqueous gel obtained by maturing the pre-reaction mixture in a pressure-resistant container, and maintaining a predetermined temperature under self-generated pressure or under gas pressure to an extent that does not inhibit crystallization, while stirring, rotating or rocking the container, or leaving it still. The reaction temperature during hydrothermal synthesis is usually 100° C. or higher, and usually 230° C. or lower, preferably 220° C. or lower, more preferably 200° C. or lower, and even more preferably 190° C. or lower. The reaction time is not particularly limited, but is usually 2 hours or more, preferably 3 hours or more, more preferably 5 hours or more, and particularly preferably 1 day or more. The upper limit is not particularly limited, but is usually 30 days or less, preferably 10 days or less, more preferably 7 days or less, and even more preferably 5 days or less. The reaction temperature may be constant during the reaction, or may be changed stepwise or continuously. After the hydrothermal synthesis, the zeolite produced is separated from the hydrothermal synthesis reaction liquid. The method for separating the zeolite from the hydrothermal synthesis reaction liquid is not particularly limited, but typically includes methods such as filtration, decantation, or direct drying. The zeolite separated and recovered from the hydrothermal synthesis reaction liquid is washed with water and dried, if necessary. The temperature during drying is usually 50° C. or higher, preferably 80° C. or higher, and more preferably 100° C. or higher. On the other hand, the temperature during drying is usually 200° C. or lower, and preferably 150° C. or lower. The drying time is not particularly limited as long as the zeolite is sufficiently dried, and is preferably 0.5 hours or more, more preferably 1 hour or more. The upper limit is not particularly limited, and is usually 200 hours or less, preferably 150 hours or less, more preferably 100 hours or less. When an organic structure-directing agent is used in the hydrothermal synthesis, the organic structure-directing agent is removed by baking after drying. The firing temperature is usually 350° C. or higher, preferably 400° C. or higher, more preferably 430° C. or higher, and even more preferably 480° C. or higher. On the other hand, the firing temperature is usually 900° C. or lower, preferably 850° C. or lower, more preferably 800° C. or lower, and even more preferably 750° C. or lower. During calcination, by setting the calcination temperature at or above the lower limit, the proportion of the organic structure-directing agent remaining can be prevented from increasing, and the organic structure-directing agent remaining in the zeolite pores can be prevented from inhibiting adsorption. On the other hand, by setting the heat treatment temperature at or below the upper limit, the zeolite framework structure can be broken, and the regular pore structure of the framework can be lost, which can prevent the adsorption selectivity from being lost. The heating time during baking is not particularly limited as long as it is a time that allows the organic structure directing agent to decompose, and is preferably 0.5 hours or more, more preferably 1 hour or more. The upper limit is not particularly limited, and is usually 200 hours or less, preferably 150 hours or less, more preferably 100 hours or less. The heat treatment may be performed in an air atmosphere, but N ２ The reaction may be carried out in an atmosphere containing an inert gas such as ethyl alcohol or oxygen. The method for producing a zeolite according to one embodiment of the present disclosure may further include exchanging cations by ion exchange. When an organic structure-directing agent is used in the synthesis, the ion exchange is usually performed after removing the organic structure-directing agent. The ions to be exchanged include H ＋ (proton), NH ４ ＋ , alkali metal ions (Li ＋ , Na＋ , K ＋ , Rb ＋ , Cs ＋ etc.), Group 2 element ions (Ca ２＋ , Mg ２＋ , Sr ２＋ , Ba ２＋ etc.), transition metal ions (Fe ２＋ , Cu ＋ , Cu ２＋ , Zn ２＋ Among these, proton, NH ４ ＋ , Li ＋ , Na ＋ , K ＋ As an ion suitable for oral administration, a proton is preferable because it can be used safely in living organisms and prevents excessive intake of various ions. Ion exchange is carried out by removing zeolite with NH ４ NO ３ , K.N.O. ３ or an aqueous solution containing nitrates or ions to be exchanged, or in some cases, an acid such as hydrochloric acid, usually at a temperature of room temperature to 100° C., followed by washing with water. Furthermore, calcination at 100° C. to 750° C. may be performed as necessary. Of the cations present inside zeolite as charge compensation for the atoms that make up the zeolite framework, 50% or more are protons (H ＋ Examples of methods for synthesizing proton-type zeolite include a method of calcining after ion exchange with ammonium ions and a method of treating by contacting with an acid. In particular, conversion to the proton type by acid treatment is preferred from the viewpoint of avoiding the calcination step during synthesis. Examples of acids to be used include organic acids such as carboxylic acids and sulfonic acids, and inorganic acids such as sulfuric acid, nitric acid, phosphoric acid, and hydrochloric acid, and these may be used alone or in combination of two or more. Among these, sulfuric acid or nitric acid is more preferred because they are strong acids and efficiently promote ion exchange. The method for producing a zeolite according to one embodiment of the present disclosure may further include performing a surface treatment on the zeolite after the hydrothermal synthesis in a solution containing a Si element source. The solution used for the surface treatment is not particularly limited as long as it is in a state in which zeolite can be treated under the conditions of the surface treatment, and may be a solution of a Si compound with a solvent added, a liquid without adding a solvent, or a sol or gel. Here, the solvent may be water or an organic solvent. In addition, solvents that are in a liquid state under pressure at a temperature equal to or higher than the boiling point are also included. In this case, the pressure may be either autogenous pressure or pressure. Furthermore, the liquid for surface treatment is required to contain at least a Si compound, and may contain, for example, an Al compound as another element source (compound). Examples of the Si compound that can be used include alkyl halide silanes such as trichloroethylsilane, dichlorohexylmethylsilane, and chlorotrimethylsilane, alkylalkoxysilanes such as methyltriethoxysilane, 3-aminopropyltriethoxysilane, and 1,1,3,3-tetramethoxy-1,3-dimethylpropanedisiloxane, organosilicon compounds having siloxanes such as hexamethyldisiloxane, organosilicon compounds having silazanes such as hexamethyldisilazane, silicates such as tetramethoxysilane and tetraethoxysilane, silicate oligomers such as methylsilicate oligomers and ethylsilicate oligomers, amorphous silica, fumed silica, colloidal silica, silica gel, sodium silicate, and silica sol. These Si compounds may be used alone or in combination of two or more. As a method of treatment, the zeolite may be immersed in a liquid to form a chemical bond with the Si compound, the chemical bond may be formed after the immersion, or the chemical bond may be formed both during and after the immersion. Also, the zeolite may be brought into contact with a gas phase of a liquid evaporated by a method such as heating to form a chemical bond, or the chemical bond may be formed after the contact. The present disclosure will be described more specifically below with reference to examples, but these are not intended to limit the scope of the present disclosure. <In vitro adsorption test> The adsorption capacity of various zeolites for TMA, choline, etc. was evaluated in vitro by the following procedure. Note that the various zeolites were synthesized or obtained according to the Reference Examples described later. Test Method [Adsorption test] Glycine, lysine, and histidine were added to fasted-state simulated small intestine fluid (FaSSIF or artificial intestinal fluid) prepared according to the preparation method described in the literature (Dissolution Technologies 20(3):44-50) to prepare a reaction solvent. The concentrations of glycine, lysine, and histidine in the reaction solvent at this time were 0.30, 0.42, and 0.21 mg / mL, respectively. 2050 mg of arginine, 120 mg of choline chloride, and 80 mg of TMA hydrochloride were precisely weighed into 50 mL of 0.1 N hydrochloric acid aqueous solution prepared by diluting 1 N hydrochloric acid with purified water, and dissolved by shaking well to prepare a standard solution. 10 mg of each type of zeolite was precisely weighed into a 25 mL tube, and 5 mL of reaction solvent was added. A stir bar and 50 μL of standard solution were added to this solution. This solution was stirred for 1 hour to prepare a reaction solution. Separately, 5 mL of the reaction solvent and 50 μL of the standard solution were added to a 25 mL tube to prepare a blank stock solution. Two blank stock solutions were prepared to check for variations in the preparation. [Sample preparation] The stir bar was removed from the reaction solution, and the solution was centrifuged at 3000 rpm for 5 minutes (unless otherwise stated, centrifugation was performed at 3000 rpm for 5 minutes using a Hitachi Koki himac CF 9RX). 1.5 mL of the supernatant was placed in a 2 mL tube, and 100 μL of 1N hydrochloric acid was added (pH = 1-2). After centrifuging the solution at 10,000 rpm for 10 minutes, 1 mL of the solution was placed in a 50 mL tube, and 9 mL of purified water was added to make a sample solution. Separately, 1.5 mL of the blank stock solution was placed in a 2 mL tube, and 100 μL of 1N hydrochloric acid was added (pH = 1-2). After centrifuging this solution at 10,000 rpm for 10 minutes, 1 mL of this solution was placed in a 50 mL tube, and 9 mL of purified water was added to make a blank solution. Two blank solutions were prepared to check the variation in the preparation. Table 1 shows the reagents used in the test, and Table 2 shows the containers and equipment used in the test. [Measurement conditions] The ion chromatography was carried out under the following conditions using an Integrion RFIC system electrochemical detector manufactured by Thermo Fischer. Column: CS17 (4 x 250 mm) Guard column: CG17 (4 x 250 mm) Detector: Electrical conductivity detector Flow rate: 1.0 mL / min Eluent: Methanesulfonic acid (eluent generator) Gradient conditions: Table 3 Column oven: 30℃ Injection volume: 50 μL Suppressor: CERS500e (4mm) Measurement time: 22 minutes [Evaluation method] Based on a separately prepared calibration curve (linearity) and the calculated detection and quantification limits, the concentrations of TMA and choline in the sample solution were calculated, and the adsorption rates of each substance adsorbed onto the zeolite and the ratio of the TMA adsorption rate to choline were determined. [Calibration curve (linearity) and detection / quantitation limits] 2050 mg of arginine, 120 mg of choline chloride, and 80 mg of TMA hydrochloride were precisely weighed out, and about 25 mL of purified water was added and thoroughly stirred to dissolve. Then, purified water was added to make the volume 50 mL. Using this solution, five solutions were prepared that sandwiched the concentration of each substance added to the sample solution, and used as a calibration curve (linearity). Furthermore, the solution was diluted to a concentration where TMA and choline could be detected and quantified, and the relative standard deviation and linearity of each substance were confirmed by measuring six times, and the detection and quantification limits were calculated. The calibration curve (linearity) and detection and quantification limits were checked every three months, and the most recent results were used for the evaluation. Kinetics Test Method [TMA / choline / arginine three-component mixture adsorption rate test] 1N hydrochloric acid was diluted with purified water to prepare 0.1N hydrochloric acid solution (2.0 mL). 13.53 mg of arginine, 10.84 mg of choline chloride, and 7.42 mg of TMA hydrochloride were precisely weighed and dissolved in the solution by shaking well to prepare a standard solution. 10 mg of zeolite was precisely weighed into a 25 mL tube, and 5 mL of FaSSIF was added. A stir bar and 50 μL of standard solution were added to this solution. Each solution was sampled only once, and the same number of reaction solutions as the number of samples were prepared in the same manner. After stirring for the desired time (3 min, 10 min, 30 min, 1 h, 3 h, 6 h, 24 h, 48 h), samples were taken in the same manner as in the [Sample Preparation] of the in vitro adsorption test, and the time course of the adsorption amount of each component was calculated from the supernatant concentrations of TMA, choline, and arginine at each time point. The adsorption amount (μg / mL) on the vertical axis of Figure 3 is the value obtained by subtracting the concentration of each component in the sample solution from the concentration of each component in the blank solution. [Choline release rate confirmation test] 12.38 g of sodium chloride, 8.94 g of sodium dihydrogen phosphate dihydrate, and 0.84 g of sodium hydroxide were weighed out, and about 1.8 L of purified water was added and stirred well to dissolve, and the pH was adjusted to 6.5 with 1 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. Purified water was added to the solution to a constant volume of 2 L to obtain a phosphate buffer. Choline chloride (991.2 mg) was added to 2 mL of phosphate buffer to prepare a choline solution. 70 mg of zeolite was precisely weighed out, and 5 mL of phosphate buffer and 50 μL of the above choline solution were added. After stirring overnight at room temperature, the zeolite was filtered out and dried under reduced pressure at 40 °C for 30 minutes. The filtrate was sampled in the same manner as in the [Sample Preparation] of the in vitro adsorption test, and then further diluted 50 times with purified water, and the blank solution and sample solution were measured. 10 mg of the zeolite powder was precisely weighed and 5 mL of phosphate buffer was added. Each solution was sampled only once, and the same number of reaction solutions as the number of samples were prepared in the same manner. After stirring for the desired time (30 min, 1 h, 3 h, 8 h, 24 h), samples were taken in the same manner as in the [Sample Preparation] of the in vitro adsorption test, and the time course of the choline release amount was calculated from the choline concentration in the supernatant at each time point. Regarding the adsorption amount (μg / mL) on the vertical axis of Figure 4, the choline concentration in the blank solution was subtracted from the choline concentration in the sample solution when choline was adsorbed overnight, and the value was multiplied by 50 / 7 to obtain the adsorption amount at 0 hours, and the choline concentration in the sample solution at each time point of the release test was subtracted from the choline concentration in the blank solution to obtain the adsorption amount at each time point. In the following, each item in the table indicates the following: Maximum number of rings: The maximum number of rings of the zeolite used in this example Skeleton code: This is the skeleton code of the zeolite used in this example, and conforms to the code that specifies the skeleton structure of zeolite defined by IZA (International Zeolite Association). If the compound is other than zeolite, the name of the compound is written. Maximum sphere diameter of diffusion in pores (Å): Maximum sphere diameter of diffusion in pores of the zeolite used in this example. The numerical value of the maximum sphere diameter of diffusion in pores was referenced to the Maximum diameter of a sphere that can diffuse along in each framework code page of Zeolite Framework Types (https: / / asia.iza-structure.org / IZA-SC / ftc_table.php) of the Structure Commission of the International Zeolite Association (IZA-SC). When there are multiple values ​​for the a, b, and c axes, the maximum one is referenced. Pore ​​dimensions: pore dimensions of the zeolites used in this example Counter cation: Counter cation of the zeolite used in this example SAR: The molar ratio of SiO2 to Al2O3 in the zeolite used in this example; for Examples 70 and 78, the molar ratio of SiO2 to Al2O3 in the raw zeolite before surface treatment (In vitro) TMA adsorption rate: TMA adsorption rate in the adsorption test carried out in this example (In vitro) Choline adsorption rate: Choline adsorption rate in the adsorption test performed in this example (In vitro) TMA / choline: The value obtained by dividing the TMA adsorption rate in the adsorption test performed in this example by the choline adsorption rate XRPD half-width: the half-width (unit: ° (2θ)) of the maximum peak (hereinafter referred to as 2θ = 7.9000 ° ± 0.5000 °) in the powder X-ray powder diffraction (hereinafter referred to as XRPD) of the MFI zeolite used in this example. Zeolite before acid treatment: Example number of the zeolite before acid treatment carried out in this example Acid: Name of the acid reagent used in this example Acid treatment temperature: the temperature of the acid treatment carried out in this example Acid treatment time: the time of the acid treatment carried out in this example Na residual ratio: Na residual ratio in the zeolite after the acid treatment carried out in this example. The Na residual ratio was calculated from the Na / Al calibration curve in XRF, with the zeolite of Example 48 before ion exchange being set at 100%. Raw zeolite: Example number of the zeolite used as the raw material for the surface treatment reaction in this example Raw zeolite SAR: The molar ratio of SiO2 to Al2O3 in the zeolite used as the raw material for the surface treatment reaction in this example. Surface treatment reagent: Surface treatment reagent used in this example Reaction conditions: reaction conditions for the surface treatment reaction carried out in this example TMA AUC change rate: d9-TMA AUC change rate of the zeolite administration group compared to the vehicle group in the fasting choline loading test performed in this example Choline AUC change rate: d9-choline AUC change rate of the zeolite-administered group compared to the vehicle group in the fasting choline loading test performed in this example Post-hydrothermal synthesis treatment: Post-treatment method after hydrothermal synthesis carried out in this example Characteristics of XRPD patterns: Characteristics of XRPD patterns of zeolites used in this example External surface area: External surface area of ​​the zeolite used in this example SEM image: SEM image of the zeolite used in this example Concomitant medications: Classification and names of the concomitant medications used in this example based on their compound properties Free molecular weight: Free molecular weight of the concomitant drug used in this example pKa: pKa of the concomitant drug used in this example. Describes acidic compounds. pKa of conjugate acid: pKa of the conjugate acid of the concomitant drug used in this example. Adsorption rate (%) to zeolite: Adsorption rate (%) of concomitant drug to zeolite used in this example result In vitro adsorption test Table 4 shows the characteristics of the zeolite such as the maximum number of rings and the framework, as well as the TMA adsorption rate and the choline adsorption rate in the in vitro adsorption test for Examples 1, 26, and 34, and Comparative Examples 1 to 5, and 7 to 21. In the zeolite with the maximum number of rings of 8, the pore size is smaller than the molecular size of TMA or choline, and it is considered that the adsorption of TMA or choline into the pores did not occur. Although choline adsorption was observed in Comparative Example 16, it is considered that this was due to the contribution of surface adsorption. In zeolites with a maximum number of rings of 10, both choline and TMA were efficiently adsorbed, except for HEU zeolite. In particular, in MFI zeolites, there were compounds that completely adsorbed the TMA in the system (Examples 26 and 34), and these compounds preferentially adsorbed TMA over choline. In HEU zeolites, the 10-ring pores are collapsed, and the maximum spherical diameter of diffusion in the pores is small at 3.67 Å, ​​so it is believed that TMA did not adsorb into the pores. Although zeolites with a maximum ring number of 12 adsorb both choline and TMA, they are not selective for TMA. This is thought to be because the pore size is larger than that of TMA and choline, and TMA and choline cannot be distinguished from each other. There was almost no adsorption of TMA using common adsorbents such as activated carbon (Comparative Example 1) and molecular sieves 4A (Comparative Examples 4 and 5), the potassium adsorbent Lokelma (registered trademark) used as a drug for hyperkalemia (Comparative Example 2), and clinoptilolite used in zeolite supplements in the United States (Comparative Example 3). For the MFI zeolites (maximum number of rings: 10) of Examples 2 to 35 and 37 to 64, and Comparative Examples 6 and 22, the silica / alumina ratio (hereinafter, referred to as SAR), counter cation, half-width of the 2θ=7.9° peak in XRPD, and in vitro adsorption test results are summarized in Tables 5-1 and 5-2. When the SAR was less than 33.0, the TMA / choline selectivity ranged from about 1 to 3. When the SAR was between 33.0 and 79.4, the TMA / choline selectivity was generally high, and the TMA adsorption rate was also high. When the SAR was greater than 79.4, the TMA / choline selectivity was generally high, but the TMA adsorption rate tended to decrease compared to when the SAR was between 33.0 and 79.4. For MFI zeolites with a TMA adsorption rate of less than 60.0% or a choline adsorption rate of more than 40.0%, and for MFI zeolites with a TMA adsorption rate of 60.0% or more and a choline adsorption rate of 40.0% or less, the distribution of the number of compounds at half width of the 2θ=7.9° peak in XRPD is shown in a histogram in FIG. 1. In MFI zeolite, not only SAR correlates with TMA / choline selectivity, but also the quality of crystals, i.e., the peak half-width of XRPD, is thought to correlate with TMA / choline selectivity. In compounds with TMA adsorption rate of 60.0% or more and choline adsorption rate of 40.0% or less, the frequency of the smaller half-width was higher, and all were 0.15° or less. On the other hand, in compounds with TMA adsorption rate of less than 60.0% or choline adsorption rate of more than 40.0%, the peak half-width exceeded 0.15°. According to the Scherrer equation, the smaller the peak half-width, the larger the crystallite size of the zeolite. It is assumed that zeolites with larger crystallite sizes are more affected by the diffusion rate in the crystal pores, and therefore the adsorption of TMA is prioritized over choline. Acid Treatment Using the zeolite of Example 50 (maximum number of rings: 10, skeleton code: MFI), the stability of the skeleton under acidic conditions was confirmed. The results are summarized in Table 6. The XRPD half-width did not change significantly under any of the conditions, so it is believed that the MFI skeleton structure was maintained. The TMA adsorption rate did not decrease due to the acid treatment, and the choline adsorption rate did not change significantly either. Using the zeolite of Example 48 (maximum number of rings: 10, skeleton code: MFI) which was only subjected to a drying treatment after hydrothermal synthesis, the effect of differences in protonation treatment on the Na / H exchange efficiency was confirmed (Table 7). Considering the residual Na ratios of the zeolites in Examples 68 and 69, it is believed that the Na / H cation exchange reaction reached equilibrium in a 1 mol / L nitric acid aqueous solution with stirring at room temperature for about 1 hour. The residual Na ratio at this time was comparable to that in the case of proton-type zeolite produced by ammonium ion exchange and calcination (Example 49). Surface Treatment The change in adsorption capacity of zeolite due to surface treatment was confirmed. The results of the study are summarized in Table 8. The in vitro TMA / choline adsorption selectivity was improved by surface treatment of all compounds. Regarding low molecular surface treatment reagents (Comparative Example 23, Examples 70 and 72-76), the TMA adsorption rate decreased in the zeolites of Examples 74 and 76, which were treated with surface treatment reagents containing octadecyl groups, which are long alkyl chains. One possible reason for this is that the internal pores were blocked by the long alkyl chains. Regarding the polymer surface treatment reagents (Examples 77-88), the change in the choline adsorption rate was small when reacted by the vapor method (Examples 77 and 80), so it is considered that the surface treatment reaction was insufficient by the vapor method. Whether toluene-2 ​​conditions or neat conditions were better depended on the polymer surface treatment reagent. Counter Cation The effect of differences in counter cations on adsorption capacity was confirmed using zeolites of Examples 34 to 36, 71, and 89 (maximum number of rings: 10, skeleton code: MFI) that were synthesized under the same hydrothermal synthesis conditions but had different counter cations (Table 9). The counter cation is H + From Li + , Na + , K + or NH4 + In the case of the proton-type, the in vitro TMA / choline adsorption selectivity did not decrease significantly. For oral use, the proton-type is preferable because it is less likely to affect the body due to excessive ion intake. BET specific surface area, particle size distribution The results of the BET specific surface area and external surface area obtained from the BET surface adsorption test for the zeolites of Examples 5, 11, 19, 26, 34, 38, 49, 52 and 53 and Comparative Examples 6 and 22 (maximum number of rings: 10, skeleton code: MFI) are shown in Table 10. External surface area is 30 m2 For compounds with a molecular weight of more than 10000 / g, the selectivity of TMA adsorption relative to choline was low. In adsorption using the internal pores of zeolite, the selectivity of TMA adsorption relative to choline increases by recognizing the difference in molecular size, but for compounds with a large external surface area, the contribution of adsorption on the external surface of the zeolite particles, which does not recognize the difference in molecular size, becomes large, resulting in low selectivity. Particle size distribution The results of particle size distribution for the zeolites of Examples 26 and 34 and Comparative Examples 6 and 22 (maximum number of rings: 10, skeleton code: MFI) are shown in Table 11-1 and FIG. In Comparative Examples 6 and 22, there are two peaks in the frequency distribution, the first peak being 1 μm or less, reflecting the small cumulative frequency 10% diameter (<2.5 μm). On the other hand, in Examples 26 and 34, there is one peak in the frequency distribution, and the cumulative frequency 10% diameter is large (>2.5 μm). Similarly, the median diameters of Examples 26 and 34 are larger than those of Comparative Examples 6 and 22. In Comparative Examples 6 and 22, the external surface area is larger than that of Examples 26 and 34, which is thought to reflect the difference in particle size. In addition, a smaller particle size is also correlated with a lower selectivity of TMA adsorption to choline. [In vitro adsorption test using low doses of zeolite] In vitro adsorption tests were carried out using low doses of the zeolites of Examples 26 and 34. The in vitro adsorption tests were carried out in the same manner as in the previously described [Adsorption Test] except that the amount of zeolite added was changed from 10 mg to 3 mg or 1 mg. The results are shown in Table 11-2. For zeolites with high TMA adsorption rate and TMA / choline selectivity, it is believed that the ratio of TMA adsorption rate / choline adsorption rate can be improved by reducing the amount of zeolite added in the in vitro adsorption test. Kinetics studies The time course of the adsorption amounts of TMA, choline, and arginine for the zeolites of Example 26, Example 34, and Comparative Example 6 (maximum number of rings: 10, skeleton code: MFI) is shown in FIG. As for TMA, the adsorption of each compound reached a plateau in a short time. Arginine was adsorbed in Comparative Example 6, but not in Examples 26 and 34. As for choline, the adsorption reached a plateau within 3 minutes of the start of the adsorption test in Comparative Example 6, but did not reach a plateau in Examples 26 and 34. The adsorption process of each component on zeolite is considered to proceed in the order of (1) surface adsorption, (2) adsorption into the surface layer pores, and (3) diffusion into the pores to the deep layer. Even if (1) is fast, if the adsorption and diffusion into the pores of (2) and (3) are slow, it becomes the adsorption rate-determining process. The difference in the adsorption rate of TMA and choline in Examples 26 and 34 is considered to reflect the difference in the rate of the adsorption process in the pores of (2) and (3). That is, choline, which has a larger molecular size than TMA, is slower than TMA in the adsorption and diffusion process in the pores due to steric hindrance, etc. In Comparative Example 6, choline, TMA, and arginine are mainly adsorbed by surface adsorption, and no difference in adsorption rate occurs, but in Examples 26 and 34, which have a large particle size, the influence of the diffusion rate in the pores becomes large, and it is considered that the adsorption rate of choline becomes significantly slower. In addition, arginine is a molecule even larger than choline, and is not adsorbed in Examples 26 and 34, which have a small external surface area and are mainly adsorbed in the pores. From the particle size distribution and the outer surface area, it is confirmed that the particle diameters of Examples 26 and 34 are larger than that of Comparative Example 6. The time course of the choline release amount for Comparative Examples 6 and 22, and Examples 26 and 34 is shown in Figure 4. In the release test, Comparative Examples 6 and 22 released a large amount of choline, and the release reached a plateau within 1 hour. On the other hand, Examples 26 and 34 released a small amount of choline, and it took about 8 hours for the release to reach a plateau. In Comparative Examples 6 and 22, which have a large outer surface area, choline was mainly adsorbed on the outer surface, so that the contribution of the choline diffusion process in the pores was small, and re-release was considered to have been rapidly performed. <Calculation> To clarify the difference in the adsorption rates of TMA and choline on MFI zeolite and the reason for the TMA / choline selectivity, we performed first-principles calculations based on density functional theory to analyze the adsorption process. Calculation method Application and version used: VASP (Vienna Ab initio Simulation Package) ver.6.3.2 (calculation execution (Masayoshi Mikami, Mitsubishi Chemical Corporation)) Density functional theory: Exchange-correlation energy is generalized density gradient correction (GGA-PBE), dispersion force correction is DFT+D3 (Grimm). PAW method (cutoff energy of plane wave basis is 400 eV). k-point sampling is Γ point, threshold of SCF calculation is 1.0×10 -6 eV, structural optimization force threshold 1.0×10 -5 eV / Å Computational model A periodic slab model corresponding to the

[0010] surface of MFI zeolite and a periodic slab model corresponding to the

[0100] surface were prepared in accordance with the data described in the paper (ACS Catalysis 2020 10, 3297-3312). Here, when placing TMA and choline in the surface model, TMA was treated as a neutral molecule, and choline was treated as a monovalent cation molecule. In addition, in the calculation of the monovalent cation state, a calculation with a uniform background charge of the opposite sign is required to maintain the charge neutrality of the entire system, but in VASP, if the number of electron occupations (NELECT) is adjusted to perform the calculation in a state corresponding to a monovalent cation, the calculation with the background charge distributed automatically can be performed. The central position in the thickness direction (z-axis direction) of the zeolite layer of each surface model was set as the reference (z = 0), and the nitrogen atom of the TMA molecule or the nitrogen atom of the choline molecule was placed there, and the stable arrangement of the molecules was obtained by optimizing the atomic position other than the z coordinate of the nitrogen atom (internal adsorption). Furthermore, the z coordinate of nitrogen was moved 1 Å at a time toward the surface, and each time, an optimization calculation was performed for the atomic positions other than the z coordinate of nitrogen. The point where the total energy of each molecule is lowest near the surface (z = 8-11 Å) was set to 0 kcal / mol and used as the energy reference point. In addition, the point where the energy barrier is highest when penetrating from the surface into the zeolite (z = 5-7 Å) was set as the energy barrier maximum point. Calculation result The energy profiles for the adsorption process of TMA or choline from the

[0010] and

[0100] faces are shown in Figure 5. The energy reference point, the highest point of the energy barrier, and the cross-sectional structure of the zeolite layer during internal adsorption are shown in Figures 6-1, 6-2, 6-3, and 6-4. The structure of the highest point of the energy barrier of the

[0010] model from the z-axis perspective is shown in Figure 7. The energy barrier for TMA and choline molecules when entering zeolite from the

[0100] face is about 5 kcal / mol (energy difference within 1 kcal / mol of quantum chemical precision), and it is considered that there is no difference in the adsorption rate. On the other hand, the energy barrier for TMA molecules when entering zeolite from the

[0010] face is about 10 kcal / mol, while it is about 15 kcal / mol for choline molecules, and it is predicted that the adsorption rate of choline molecules is slower than that of TMA. This calculation result is considered to support the experimental result that the

[0010] face is a crystal face with high TMA / choline selectivity (results of "SEM images, external surface area, and fasting choline tolerance test efficacy" described later). TMA, a tertiary amine, has a triangular pyramidal molecular structure with nitrogen at the apex, and can pass through an elliptical pore shape by aligning the short and long axes of the molecule, but choline, a quaternary ammonium ion, is a regular tetrahedral shape with nitrogen at the center, and cannot be aligned with the elliptical shape, which can be considered from Figure 7 that steric hindrance occurs when passing through. The three-dimensional channels of MFI zeolite are composed of linear

[0010] channels and sinusoidal

[0100] channels connected to each other, and molecules diffuse in the

[0001] direction by alternating between the

[0010] and

[0100] channels. Since the steric hindrance in the process of choline penetrating the

[0010] surface is assumed to occur in the interpore movement beyond the

[0010] surface inside the crystal as well, it is assumed that the diffusion rate of choline is slower than that of TMA in the intracrystalline diffusion in the

[0010] and

[0001] directions. This is consistent with the experimental results showing that TMA / choline selectivity is high in coffin-shaped crystals long in the

[0001] direction (results of "SEM images, external surface area and fasting choline tolerance test efficacy" described later), and also with the results of the kinetics test showing that the adsorption rate of choline is slow in Examples 26 and 34 with large particle sizes (results of the previously mentioned "kinetics test"). <Fasting Choline Tolerance Test> Test Method Seven-week-old male C57BL / 6 mice were fasted for 12 hours, and then orally administered d9-choline chloride (Toronto Research Chemicals Inc.) dissolved in distilled water, 0.5 w / v% methylcellulose 400 solution, and zeolite suspended in sterile water (Fujifilm Wako Pure Chemical Industries, Ltd.) at doses of 78.78 mg / kg (60 mg / kg as d9-choline) and 500-2000 mg / kg, respectively. Blood was then collected from the tail vein 1, 2, 4, 6, 8, and 10 hours later, and the concentrations of d9-choline, d9-TMA, and d9-TMAO in plasma were measured by LC / MS / MS. For d9-choline, d9-TMA, and d9-TMAO, the plasma concentration over time was plotted with the plasma concentration on the vertical axis and the time after administration on the horizontal axis, and the area under the curve (AUC) up to 10 hours after administration was calculated. The pharmacological effect of zeolite was confirmed by comparing these values ​​between the non-zeolite group (vehicle group) and the zeolite administration group. In addition, the pharmacological effect of each zeolite was compared using the AUC change rate, which was the amount of AUC change from the vehicle group normalized by the vehicle group AUC. The AUC change rate was calculated from the following formula. result Fasting choline tolerance test For the zeolites of Examples 1, 5, 9, 13, 15, 26, 34 and 55, and Comparative Examples 8, 6 and 22, the compound profiles and the results of the fasting choline loading test are summarized in Table 12. All compounds were tested at a dose of 500 mg / kg (unless otherwise specified below, the results of the fasting choline loading test refer to those at a dose of 500 mg / kg). All of the compounds reduce the AUC of d9-TMA compared to the vehicle group. In the zeolites of Comparative Examples 6, 8, and 22, which have low TMA / choline selectivity in the in vitro adsorption test, the AUC reduction rate of d9-choline is equal to or greater than that of d9-TMA. Compounds with high TMA / choline selectivity and high TMA adsorption capacity in the in vitro adsorption test have high AUC reduction rates of d9-TMA and low AUC reduction rates of d9-choline. Choline is a nutrient, and compounds that inhibit the absorption of choline are not desirable. The "AUC reduction rate" refers to the value obtained by multiplying the "AUC change rate" by minus 1. FIG. 8 shows the time course of d9-TMA plasma concentration and its AUC when multiple doses of the zeolite of Example 34 were administered to choline-loaded mice under fasting conditions. The zeolite of Example 34 dose-dependently decreased the plasma d9-TMA concentration and AUC, and at the highest dose of 2000 mg / kg, it almost completely suppressed the increase in plasma d9-TMA, which is considered to have adsorbed most of the d9-TMA in the digestive tract. FIG. 9 shows the time course of plasma concentrations of d9-choline and d9-TMA when a large dose of the zeolite of Comparative Example 6 was administered to choline-loaded mice under fasting conditions. In the case of the zeolite of Comparative Example 6, which has low TMA / choline selectivity, the time to reach the maximum plasma concentration of d9-TMA (hereinafter, T max ) is delayed from the vehicle group, and T maxThe decrease in d9-TMA plasma concentration after this point becomes more gradual. In the 2000 mg / kg group, the d9-TMA plasma concentration increases gradually from 4 to 10 hours. The plasma choline concentration is always kept at a low level at all doses. From these experimental results, it is considered that (1) the absorption of choline in the digestive tract is suppressed by the adsorption of choline by the compound in the upper digestive tract and small intestine, (2) the release of choline from the compound in the large intestine, followed by (3) the decomposition of choline to TMA by bacteria, and (4) the absorption of TMA from the large intestine. In other words, it is considered that the compound temporarily adsorbs choline and re-releases it in the large intestine, thereby increasing the amount of TMA generated in the intestinal tract. It is considered that an in vitro TMA / choline adsorption selectivity of about 1 is not enough to fully counteract the effect of the increase in TMA absorption amount due to choline delivery in the large intestine (Table 12; zeolites of Comparative Examples 6, 8, and 22). The choline release rate of the zeolites of Comparative Examples 6 and 22 is fast, as confirmed by Figure 4. Time course of release amount. Zeolite countercations, post-treatment methods and efficacy in fasting choline tolerance tests The zeolites of Examples 34, 35, and 68 were compared within the same test to see whether differences in counter cations and post-treatment methods had any effect on the fasting choline tolerance test (Table 13). Example 35 is a Na-type zeolite that was not proton-exchanged, Example 34 is a proton-type zeolite obtained by calcining the Na-type after ammonium ion exchange, and Example 68 is a proton-type zeolite obtained by treating the Na-type with nitric acid. The efficacy of both zeolites was confirmed in a fasting choline loading test. Compared to the proton-type zeolite calcined after ammonium ion exchange, the proton-type zeolite treated with nitric acid showed a higher reduction in the AUC of d9-TMA. Zeolite surface treatment and its efficacy in fasting choline tolerance test In order to confirm the effect of zeolite surface treatment on the pharmacological effect, the zeolites of Examples 34, 70 and 78 were administered to fasting choline-loaded mice, and their pharmacological effects were compared. Table 14 summarizes the compound profile and the results of the fasting choline loading test. The zeolites of Examples 70 and 78 were obtained by subjecting the zeolites obtained by Example 34 or a similar synthesis method to surface treatment. The surface treatment resulted in a decrease in d9-TMA AUC at the same level or higher than that before surface treatment, while preventing a decrease in d9-choline AUC. The effect of preventing choline adsorption by the surface treatment was also confirmed in a fasting choline loading test. Quartz in Zeolite and the Efficacy of the Fasting Choline Tolerance Test For the zeolites of Examples 34 and 52, the compound profiles and AUC changes in the fasting choline loading test are shown in Table 15. Figure 10 shows the XRPD patterns of Example 34 (upper row) and Example 52 (lower row). The vertical axis is intensity (cps) and the horizontal axis is diffraction angle 2θ (°). It can be seen that Example 52 contains many characteristic quartz peaks around 2θ=21° and 27° compared to Example 34. In the zeolite of Example 52, which contains a large amount of quartz, the d9-TMA AUC reduction rate in the fasting choline loading test was small (Table 15). Quartz does not have a pore structure and is considered to have no TMA adsorption effect. In other words, in Example 52, which contains a large amount of quartz, the MFI type zeolite content per weight is reduced, and the efficacy (d9-TMA AUC reduction rate) in the fasting choline loading test is considered to be lower than that of Example 34. SEM images, external surface area and fasting choline loading test efficacy For the zeolites used in the in vitro adsorption test and the fasting choline loading test, the correlation between the drug efficacy, the external surface area, and the SEM images was confirmed (Table 16-1, Table 16-2). For the zeolites of Comparative Examples 6 and 22, in which the d9-TMA AUC reduction rate and the d9-choline AUC reduction rate in the fasting choline loading test were comparable, it was confirmed from SEM images that most of them consisted of fine particles of 1 to 2 μm or less and their aggregates. On the other hand, for the zeolites (Examples 5, 26, 34, and 52), in which the d9-TMA AUC reduction rate was greater than the d9-choline AUC reduction rate in the fasting choline loading test, it was confirmed that the proportion of fine particles of 1 to 2 μm or less and their aggregates was smaller than that of Comparative Examples 6 and 22, and that the crystals had grown larger. For Examples 5, 26, and 34, which had high in vitro adsorption selectivity and a particularly large difference between the d9-TMA AUC reduction rate and the d9-choline AUC reduction rate, it was confirmed by particle observation using SEM that the crystal shape was coffin-shaped and the crystal plane of the

[0010] face was wide. The adsorption rate of choline and TMA is governed by the penetration rate of molecules from the medium into the zeolite pores and the diffusion rate of molecules in the crystal pores. In the case of MFI zeolite, which has a three-dimensional pore structure, it is considered that the penetration rate and the diffusion rate in the three-dimensional coordinate axis direction of the crystal are different due to the difference in crystal face. In MFI zeolite, the TMA / choline selectivity was high when the crystal face of the

[0010] face was wide, so it is presumed that the

[0010] face is the crystal face with the highest TMA / choline selectivity. It has been confirmed in SCIENCE, 2003, Vol 300, Issue 5618, pp. 456-460 that the widest crystal face of MFI zeolite, which has a coffin-shaped crystal shape, is the

[0010] face. In addition, as reported in J. Am. Chem. Soc. 2023, 145, 9021-9028, further selectivity improvement is expected by selectively treating the surface of the surface other than the

[0010] surface, into which choline has difficulty penetrating. In addition, since the length of the crystal axis of the coffin-shaped crystal is in the order of

[0001] axis >

[0100] axis >

[0010] axis, it is also presumed that TMA / choline selectivity is obtained during the diffusion process in the crystal pores in the

[0001] axis direction. It was confirmed in the SEM images that the more fine particles or aggregates thereof with sizes of 1 to 2 μm or less (Comparative Examples 6 and 22) or scale-like structures (Examples 19 and 53) there were, the larger the external surface area tended to be. Furthermore, a correlation was confirmed in which the larger the external surface area, the higher the d9-choline AUC reduction rate in the fasting choline loading test. Example 52, which has been confirmed to contain a large amount of quartz from the XRPD data, also has many particles other than MFI type zeolite that appear to be quartz in the SEM image, compared to Example 34. <Single-dose PK study and physiologically based pharmacokinetic (PBPK) model construction> Single intravenous administration PK study of d9-TMA and d9-TMAO d9-TMA or d9-TMAO was administered intravenously to 7-9 week-old male C57BL / 6 mice at a dose of 11.5 mg / kg or 10 mg / kg, and blood samples were taken over time. d9-TMA was also administered intravenously to 7 week-old male C57BL / 6 mice at a dose of 10 mg / kg, and urine samples were taken for 24 hours. Plasma and urinary concentrations of d9-TMA and d9-TMAO were measured by LC-MS / MS. Single oral dose PK study of d9-TMA d9-TMA was orally administered at a dose of 34.6 mg / kg to 7-week-old male C57BL / 6 mice under fasting conditions, and blood samples were taken over time. Plasma d9-TMA and d9-TMAO concentrations were measured by LC-MS / MS. PBPK model construction Report by Shimizu et al. 1) With reference to the above, a PBPK model was constructed for d9-choline, d9-TMA, and d9-TMAO when d9-choline was orally administered to mice, employing a transit model that takes into account the conversion process of d9-choline to d9-TMA by intestinal bacteria in the large intestine and the transit time from the upper gastrointestinal tract to the large intestine. A schematic diagram of the PBPK model is shown in Figure 11. In constructing the model, in vivo data from the vehicle group of the previously mentioned "fasting choline loading test" and in vivo data from a single-dose PK study were used. 1) Shimizu, M. et al. Human plasma concentrations of trimethylamine N-oxide extrapolated using pharmacokinetic modeling based on metabolic profiles of deuterium-labeled trimethylamine in humanized-liver mice. J. Toxicol. Sci. 43, 387-393 (2018). The following steps were applied to construct the PBPK model. The liver / plasma partition coefficients, blood cell / plasma partition coefficients, and plasma protein unbound fractions of d9-TMA and d9-TMAO are assumed to be the same for all species, and are based on the values ​​reported by Shimizu et al. 1) was quoted. Liver volume and hepatic blood flow were reported by Yamashita et al. 2) was quoted. ・PK parameters of d9-TMA and d9-TMAO were estimated using data from single intravenous administration PK studies of d9-TMA and d9-TMAO. Renal clearance was optimized to accurately reproduce the urinary excretion rate of d9-TMA. ・The absorption parameters of d9-TMA (including the rate constant of transit from the upper gastrointestinal tract to the large intestine and the conversion rate of d9-choline to d9-TMA) were estimated using the data of the vehicle group in the fasted choline loading study. The conversion rate was calculated by dividing the dose-adjusted AUC of d9-TMA in the vehicle group in the fasted choline loading study normalized by the dose-adjusted AUC of d9-TMA in the d9-TMA administration group in the single intravenous administration PK study by the absorption rate of d9-TMA calculated using the PBPK model. The AUC reduction rates of d9-choline and d9-TMA were the gastrointestinal absorption inhibition rates due to adsorption to zeolite (hereinafter referred to as IR, respectively). pre and IR), and the IR for the amount of zeolite administered pre The relationship between the inhibition rate of gastrointestinal absorption and the amount of zeolite administered was calculated using the Emax The 50% effective dose was calculated by fitting to the model. Assuming that d9-TMA reaches adsorption equilibrium in the digestive tract, the dissociation constant between zeolite and d9-TMA was calculated based on the following formula: digestive tract absorption inhibition rate of d9-TMA = theoretical acid amount of unadsorbed zeolite / (water volume in the large intestine × dissociation constant + theoretical acid amount of unadsorbed zeolite). The value of SimCYP (V23) manufactured by Certara was used for the water volume in the large intestine. 2) Yamashita, M. et al. Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling. Regulatory Toxicology and Pharmacology 70, 214-221 (2014). The parameters used in the PBPK model are shown in Table 16-3. Simulation of plasma concentration transition and urinary excretion amount when zeolite of Example 34 is administered A graph comparing the actual measured plasma concentrations of d9-choline, d9-TMA, and d9-TMAO with the plasma concentration time course predicted by the PBPK model when multiple doses of the zeolite of Example 34 were administered to fasted choline-loaded mice is shown in Figure 12. The predicted results of the 24-hour urinary excretion amounts calculated from the PBPK model are also shown in Table 16-4. The plasma concentration time courses of d9-choline, d9-TMA, and d9-TMAO simulated by the PBPK model largely reproduced the actually measured plasma concentration time courses. <Food-induced choline loading test> Test Method 10-week-old male C57BL / 6 mice were habituated to a day-night reversal and restricted feeding regimen and fed a choline-free diet (A21122102) (EP Trading Co., Ltd.) and were orally administered d9-choline chloride (Toronto Research Chemicals Inc.) dissolved in distilled water and zeolite of Example 34 suspended in 0.5 w / v% methylcellulose 400 solution and sterilized (Fujifilm Wako Pure Chemical Co., Ltd.) at doses of 78.78 mg / kg and 500 to 2000 mg / kg, respectively. Similarly, d9-choline chloride dissolved in distilled water and zeolite of Example 70 suspended in 0.5 w / v% methylcellulose 400 solution and sterilized were orally administered at doses of 78.78 mg / kg and 1000 mg / kg, respectively. After oral administration, the animals were placed in metabolic cages and urine was collected for 24 hours. The concentrations of d9-TMA, d9-TMAO, native TMA, and native TMAO in the obtained urine were measured by LC / MS / MS, and the 24-hour urinary excretion amount of each was calculated from the urine volume. Here, native means that the molecule is composed of the isotope element with the largest isotope abundance ratio. The results are shown in Figure 13. It was confirmed that the combined 24-hour urinary excretion amount (μmol) of d9-TMA and TMAO was dose-dependently decreased by administration of the zeolite of Example 34 compared to the vehicle group. Similarly, the combined 24-hour urinary excretion amount of native TMA and TMAO was also dose-dependently decreased. It was confirmed that the combined value of these d9 bodies and native bodies was also dose-dependently decreased. It was confirmed that the administration of the zeolite of Example 70 reduced the 24-hour urinary excretion amount of TMA and TMAO to the same extent as the administration of the zeolite of Example 34. In a choline loading test under fasting conditions, but in a fed condition where d9-choline was loaded to mimic human dietary conditions, the zeolite of Example 34 reduced the urinary excretion of d9-TMA and TMAO. This shows that even under fed conditions where there are various impurities in the digestive tract, the zeolite of Example 34 specifically recognized and adsorbed and removed TMA. It was strongly suggested that the use of zeolite with high selectivity for TMA would be effective in TMAU patients. <Clinical Dosage Prediction> The inhibition rate of gastrointestinal TMA absorption by the zeolite of Example 34 was calculated from the total urinary excretion amounts of d9-TMA and d9-TMAO in a choline loading test under feeding, and the effective dose was corrected by the ratio of the gastrointestinal TMA amounts in mice and humans to estimate the clinically effective dose of the zeolite of Example 34. Calculation of gastrointestinal TMA absorption inhibition rate In humans and rats 14 When C-TMA was orally administered, more than 95% and 80% of the radioactivity was excreted in urine 24 hours after administration, with the majority of the radioactivity being TMA and TMAO. 3, 4) Therefore, it was suggested that the amount of TMA in the digestive tract could be estimated from the total amount of TMA and TMAO excreted in urine in mice. 3) Al-Waiz M, Mitchell SC, Idle JR, Smith RL. The metabolism of 14 C-labeled trimethylamine and its N-oxide in man. Xenobiotica 1987; 17(5): 551-558 4) Al-Waiz M, Mitchell SC. The fate of trimethylamine in the rat. Drug Metab and Drug Interact 1991; 9(1): 41-48 The gastrointestinal TMA absorption inhibition rate of the zeolite of Example 34 in this test was calculated from the total urinary d9-TMA and d9-TMAO excretion amounts when vehicle or the zeolite of Example 34 was orally administered simultaneously with d9-choline, using the following formula. The typical daily intake of TMA in a Western diet is 50 mg TMA / day. 5) The threshold for urinary excretion of TMA that produces an odor in TMAU patients is 20 mg TMA / day. 6) The urinary TMAO content (as % of TMA + TMAO) was reported in the literature. 7) The inhibition rate for gastrointestinal TMA absorption in each patient group was calculated using the following formula: 5) Fennema D, Phillips IR, Shephard EA. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease. Drug Metab Dis 2016; 44:1839-1850 6) Michell SC, Smith RL. Trimethylaminuria: The Fish Malodor Syndrome. Drug Metab Dis 2001; 29:517-521 7) Shimizu M, Allerston CK, Shephard EA, Yamazaki H, Phillips IR. Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population. Br J Clin Pharmacol 2013; 77(5): 839-851 Clinical Dose Estimation The adsorption rate of zeolite is determined by the ratio of the substance to be adsorbed to zeolite. Based on this idea, when the TMA adsorption rate in mice (gastrointestinal TMA absorption inhibition rate) is equivalent to the clinically targeted TMA adsorption rate, the mouse dose (mouse effective dose) was corrected by the ratio of the standard gastrointestinal TMA amount in mice and humans, to estimate the clinically effective dose of zeolite in Example 34. The formula used for the calculation is shown below. *The total amount of d9-TMA and d9-TMAO excreted in urine (mol) in the vehicle group was divided by the urinary recovery rate (0.9) and the bioavailability of TMA (assumed to be 0.8, the same as in rats), and converted to a TMA equivalent weight. The urinary recovery rate (0.9) was calculated by dropping mouse urine into a metabolic cage, collecting it, and using the urine volume before and after dropping as an index. Calculation of the inhibition rate of gastrointestinal TMA absorption The gastrointestinal TMA absorption inhibition rates calculated from the above formula are shown in Table 17, and the clinically targeted gastrointestinal TMA absorption inhibition rates are shown in Table 18. When the zeolite of Example 34 and 60 mg / kg of d9-choline were simultaneously administered to mice, the gastrointestinal TMA absorption inhibition rates were 42.8% at 500 mg / kg, 58.4% at 1000 mg / kg, and 90.4% at 2000 mg / kg. In addition, the clinical target gastrointestinal absorption rate was calculated to be 42.6% in severe patients and 53.5% in patients considered to be the most severe in literature reports. From the above results, the gastrointestinal TMA absorption inhibition rate when the zeolite of Example 34 was administered to mice at 500 mg / kg and 1000 mg / kg was considered to be equivalent to the target inhibition rate expected for severe and most severe patients, respectively. Clinical dose estimation results The estimated clinically effective dose of the zeolite of Example 34 calculated from the above formula is shown in Table 19. The clinically effective dose expected to have a therapeutic effect on severe patients was estimated to be 793 mg / man / meal, equivalent to 500 mg / kg of the TMAU model mouse, and the clinically effective dose for the most severe patients was estimated to be 1595 mg / man / meal, equivalent to 1000 mg / kg of the same model mouse. <Si, Al elution test> Test Methods & Results For each of the zeolites of Examples 26 and 34, the elution test of Si and Al was carried out. 250 mg of zeolite was precisely weighed out, 5 mL of 1N hydrochloric acid was added, and the mixture was stirred at 37°C for 3 hours. This liquid was centrifuged. 2 mL of the supernatant was centrifuged again to obtain a new supernatant (initial elution liquid). The remaining zeolite-containing liquid was filtered using filter paper (No. 5B) to filter out the zeolite. This zeolite was added to 5 mL of newly prepared 1N hydrochloric acid, and the mixture was stirred at 37°C for 3 hours. 2 mL of the supernatant of this liquid was taken and centrifuged to obtain a new supernatant (second elution liquid). 1000 mg of each of the first and second elution liquids was weighed out, 2 mL of 38% (12N) hydrochloric acid was added, and purified water was added to make 25 mL. The Si and Al concentrations of these solutions were measured using ICP-AES, and the concentrations and elution rates of Si and Al in the elution liquid were calculated (Table 20). The elution rate was calculated by dividing the weight of Si or Al in the zeolite used in the test by the weight of Si or Al present in eluate equivalent to 5 mL, assuming that the counter cation of the zeolite is a proton and that the zeolite does not contain water. The elution rate of Al in the zeolite of Example 34 was 10% or less, and in the zeolite of Example 26, it was about 0.1%. The elution of Si was 0.1% or less in all compounds. In addition, the amount of eluted Si and Al was reduced during re-elution compared to the initial elution. This is thought to be because the trace impurities other than zeolite that were present during the initial elution and the incomplete structure of the zeolite surface were no longer present during re-elution. It is thought that the amount of eluted Si and Al in the digestive tract during administration to a living body can be reduced by adding an acid treatment as a post-treatment after zeolite synthesis. When administered to living organisms, it is expected that minute amounts of Si and Al will be eluted in gastric acid, so the effects on the body must be considered. Even if the same amount of Al elutes in the digestive tract as in this test when a person weighing 70 kg takes 3 g of the zeolites of Examples 26 and 34 per day, the amount of Al elution will not exceed the provisional tolerable weekly intake of Al (2 mg / kg body weight / week) set by the Joint FAO / WHO Expert Committee on Food Additives (JECFA), and there is likely to be little concern about safety. <Gastrointestinal Absorption Evaluation Test> The fecal excretion rates of the zeolites of Examples 26 and 34, when each was orally administered once to rats, were calculated from the Si and Al concentrations in the feces, and it was shown that almost the entire amount of the administered zeolite was excreted in the feces and was hardly absorbed from the digestive tract. Test Method The zeolite of Example 26 or Example 34 was orally administered once to 6-week-old male Crl:CD(SD) rats at a dose of 2000 mg / kg, and feces were collected up to 48 hours after administration. Ultrapure water was added to the collected feces, and homogenates were prepared using a polytron and freeze-dried. An appropriate amount of dried feces was weighed out, and the samples were dissolved by incineration, alkali salt fusion, dilute acid dissolution, etc., and ICP emission spectrometry was performed to measure the fecal Si and Al concentrations. In addition, feces obtained from 24 hours before administration of each zeolite until just before administration were used as blank feces, and a specified amount of each zeolite was added to the blank dried feces that were homogenized and freeze-dried in the same manner as above, and the fecal Si and Al concentrations were measured by the same experimental procedures as above, to create a calibration curve of the fecal Si and Al concentrations against the added zeolite concentration, and the fecal excretion rate of zeolite was calculated. result The fecal excretion rates of the zeolite of Example 26 were 99% to 118% (based on Si concentration) and 98% to 116% (based on Al concentration), and the fecal excretion rates of the zeolite of Example 34 were 91% to 104% (based on Si concentration) and 96% to 109% (based on Al concentration). <Safety Testing> Using various types of zeolites, cytotoxicity tests, single-dose toxicity tests, one-week toxicity tests, and in vitro genotoxicity tests were conducted, and high safety was confirmed in all tests. The details are shown below. Cytotoxicity Testing The cytotoxicity of each of the zeolites of Comparative Examples 6, 10, 12, 15, and 16, and Examples 9, 13, 25, 26, 58, 70, and 79 was evaluated using HepG2 cells based on the number of viable cells as an index of ATP amount at a maximum dose of 500 μg / mL. 50 ) was confirmed to be higher than 500 μg / mL. Single-dose toxicity test The zeolite of Example 34 was orally administered once to 6- or 7-week-old Crl:CD(SD) rats (male) at a maximum dose of 6000 mg / kg / day (2000 mg / kg three times a day), and a tolerability evaluation was performed based on the general condition, body weight, food intake, and macroscopic examination (external surface, thoracic and abdominal cavities, and their internal organs and tissues). It was confirmed that the zeolite was tolerable up to the maximum dose. One-week toxicity test The zeolite of Example 34 was orally administered repeatedly to 6 or 7 week-old Crl:CD(SD) rats (male) at a maximum dose of 6000 mg / kg / day (2000 mg / kg three times a day) for one week, and the general condition, body weight, food intake, ophthalmological examination, hematological examination (red blood cell count, hemoglobin concentration, hematocrit value, mean red blood cell volume, mean red blood cell hemoglobin content, mean red blood cell hemoglobin concentration, red blood cell volume distribution width, reticulocytes, platelet count, mean platelet volume, white blood cell count, white blood cell differential, prothrombin time, activated partial thromboplastin time), blood biochemistry examination (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, glutamate dehydrogenase, glucose, total bilirubin, direct bilirubin, indirect bilirubin, total bile acid, The following items were examined: urea nitrogen, creatinine, total cholesterol, triglyceride, inorganic phosphorus, calcium, sodium, potassium, chloride, total protein, protein fraction, albumin / globulin ratio), organ weights (heart, thymus, spleen, lungs, liver, kidneys, pituitary, adrenal gland, testis, epididymis, prostate, brain), macroscopic examination (external surface, thoracic and abdominal cavities, and their internal organs and tissues), histopathological examination (heart, sternum, sternal bone marrow, femur, knee joint, femoral bone marrow, thymus, spleen, mesenteric lymph nodes, bronchi, lungs, stomach, duodenum, jejunum, ileum, Peyer's patches, cecum, colon, rectum, liver, pancreas, kidneys, adrenal gland, testis, brain, sciatic nerve, eye, optic nerve, skeletal muscle), and bone marrow micronucleus evaluation. No toxicological changes were observed in any of the dose groups. In vitro genotoxicity tests The zeolite of Example 13 was used to evaluate the mutagenicity of Salmonella typhimurium TA100, TA98, TA1537, TA1535, and Escherichia coli WP2uvrA based on the number of revertant colonies under two conditions (without and with metabolic activation system) at a maximum dose of 5000 μg / plate, which is the upper limit specified in the guidelines. The results were negative (Ames test). The zeolite of Example 13 was used in CHL / IU cells to evaluate the micronucleus induction potential under three conditions (6 hours of treatment without metabolic activation, 6 hours of treatment with metabolic activation, and 24 hours of treatment without metabolic activation) with the lowest precipitation dose of 0.5 μg / mL as the maximum dose, and the result was negative. (In vitro micronucleus test) <Adsorption selectivity test> We conducted adsorption tests on zeolite to confirm the adsorption selectivity of ions and compounds in the body that may be adsorbed competitively with the compounds to be removed or that may cause problems when adsorbed to humans. Alkaline metals, alkaline earth metals, ammonia Adsorption tests of alkali metals, alkaline earth metals, and ammonia were carried out for each of the zeolites in Examples 5, 34, and 70 and Comparative Example 6. 3 mg of zeolite was precisely weighed and dissolved in a cation mixed standard solution II (Kanto Chemical, Li + : 0.5 mg / mL, Na + and NH4 + : 2 mg / mL, K + , Mg 2+ and Ca 2+ The mixture was centrifuged, and the various components in the supernatant were measured by ion chromatography to calculate the adsorption rate, with the results shown in Table 21-1. For the three compounds other than Example 5, which had a high SAR, NH4 + and K + Li was adsorbed. + , Na + , Mg 2+ and Ca 2+ The adsorption rate was low for all compounds. Alkali metals and ammonia The zeolite of Example 4 was subjected to an adsorption test of alkali metals and ammonia. 3 mg of the zeolite was precisely weighed and dissolved in a cation mixed standard solution III (Kanto Chemical, Na + , NH4 + and K +0.5 mL of 100 mg / mL NaCl and 9.5 mL of purified water were added and stirred at room temperature for 1 hour. The liquid was centrifuged, and the various components in the supernatant were measured by ion chromatography to calculate the adsorption rate, resulting in the results shown in Table 21-2. The zeolite of Example 4, which has a high SAR, has a high adsorption rate of Na. + , NH4 + and K + There was almost no adsorption. Alkali metal / ammonia (in the presence of TMA) For each of the zeolites of Examples 34 and 70 and Comparative Example 6, an adsorption test of alkali metals and ammonia in the presence of TMA was carried out. 80 mg of TMA hydrochloride was precisely weighed out and dissolved in 50 mL of 0.1 N hydrochloric acid aqueous solution prepared by diluting 1 N hydrochloric acid, and the solution was shaken well to prepare a TMA standard solution. 3 mg of zeolite was precisely weighed out and dissolved in cation mixed standard solution III (Kanto Chemical, Na + , NH4 + and K + 0.5 mL of 100 mg / mL TMA solution, 9.5 mL of purified water, and 50 μL of TMA standard solution were added and stirred at room temperature for 1 hour. The solution was centrifuged, and the various components in the supernatant were measured by ion chromatography to calculate the adsorption rate, resulting in the results shown in Table 21-3. In the presence of TMA, all of the compounds adsorbed TMA, and the adsorption rate was reduced by 10% compared to when TMA was not present. + and K + The adsorption of was reduced (see Table 21-1). Each cation must be dehydrated as it is absorbed from water into the zeolite pores. The heat of hydration is Li + >Na + >K + ~NH4 + Since there was not enough stabilization energy in the pores to compensate for this heat of hydration, Li + , Na + It is considered that the adsorption of Mg was weak. 2+ , Ca 2+is a divalent cation, and in order for it to be stabilized by electrostatic interactions in the zeolite pores, multiple acid sites must exist within the unit pore. The SAR ratio of the zeolite used in this study was such that the proportion of multiple acid sites in the unit pore was low, and it was not suitable for adsorption of divalent cations. + and K + It was found that the adsorption of TMA was prioritized over the adsorption of . essential metal elements Adsorption tests of essential metal elements for humans were carried out for each zeolite of Examples 5, 34, and 70 and Comparative Example 6. 3 mg of the compound was precisely weighed out, and 9.25 mL of 0.1 mol / L nitric acid aqueous solution prepared by diluting 1 mol / L nitric acid aqueous solution 10 times with purified water, 0.15 mL of 0.1 mol / L cobalt (II) nitrate aqueous solution, 0.14 mL of 0.1 mol / L manganese (II) nitrate aqueous solution, 0.16 mL of 0.1 mol / L zinc (II) nitrate aqueous solution, 0.16 mL of 0.1 mol / L copper (II) nitrate aqueous solution, and 0.14 mL of 0.2 mol / L iron (III) nitrate aqueous solution were added and stirred at room temperature for 1 hour. This liquid was centrifuged, and high-purity nitric acid (60%) was added to 1000 μL of the supernatant, and the mixture was diluted with purified water to a constant volume of 50 mL (HNO3 2%). The components were measured by ICP-AES and the adsorption rates were calculated, with the results shown in Table 22. The reagents used in the reaction are shown in Table 23. Amino acids For each of the zeolites of Example 5, Example 34, and Comparative Example 6, an amino acid adsorption test was carried out using the following two types of mixed amino acid solutions. Amino acid mixture standard solution 3 mg of zeolite was precisely weighed, 1.0 mL of mixed amino acid standard solution, AN type (high concentration type, Fujifilm Wako Pure Chemical Industries, Ltd.), 1.0 mL of mixed amino acid standard solution, B type (high concentration type, Fujifilm Wako Pure Chemical Industries, Ltd.), and 8 mL of phosphoric acid buffer were added, and the mixture was stirred at room temperature for 1 hour. The mixture was centrifuged, the supernatant was ultrafiltered (MWCO = 10,000), and the membrane-passed liquid was subjected to amino acid analysis. The amino acid mixed standard solution, AN type (high concentration type), is a mixed standard solution of 25 kinds of amino acids including acidic and neutral amino acids, and the concentrations of each component are L-aspartic acid, L-threonine, L-serine, L-glutamic acid, glycine, L-alanine, L-citrulline, L-valine, L-cystine, L-methionine, L-isoleucine, L-leucine, L-tyrosine, L-phenylalanine, β-alanine, DL-3-aminoisobutyric acid, L-hydroxyproline, and L-proline at 2.5 μmol / mL each, O-phospho-L-serine, taurine, O-phosphoethanolamine, DL-2-aminobutyric acid, and L-cystathionine at 1.25 μmol / mL each, sarcosine at 6.25 μmol / mL, and urea at 50 μmol / mL. In addition, the amino acid mixed standard solution, type B (high concentration type), is a mixed standard solution of 12 amino acids including three basic amino acids, and contains 2.5 μmol / mL each of 4-aminobutyric acid, ethanolamine, ammonium chloride, 5-hydroxy-DL-lysine, L-ornithine, L-lysine, 1-methyl-L-histidine, L-histidine, 3-methyl-L-histidine, L-anserine, L-carnosine, and L-arginine. Unstable amino acid mixture 3 mg of zeolite was precisely weighed out, and 10 mL of amino acid mixture (containing 40.8 μg (0.20 μmol) of L-tryptophan, 29.2 μg (0.20 μmol) of L-glutamine, and 26.4 μg (0.20 μmol) of L-asparagine per mL of purified water) was added and stirred at room temperature for 1 hour. This solution was centrifuged, and the supernatant was ultrafiltered (MWCO=10,000), and the membrane-passed liquid was subjected to amino acid analysis. The reagents used are listed in Table 24. Amino acid analysis was performed using a high-speed amino acid analyzer L-8900 (Hitachi High-Tech) by the ninhydrin color reaction method (post-labeling method). 0.8 mL of the amino acid mixed standard solution, AN type, and 0.8 mL of the amino acid mixed standard solution, B type, were mixed and the volume was adjusted to 10 mL with purified water to create a calibration curve. 10 μL of the membrane permeate was then injected, and the concentrations of various amino acids in the membrane permeate were calculated using a one-point calibration curve from the peak areas, and the adsorption rates were calculated. The adsorption rates of proteinogenic amino acids and non-proteinogenic amino acids are shown in Tables 25 and 26, respectively. For the silicalite of Example 5, none of the proteinogenic amino acids were adsorbed, and for the zeolite of Example 34, no proteinogenic amino acids were adsorbed except for L-asparagine and L-glutamine. For the zeolite of Comparative Example 6, adsorption of the basic amino acids L-lysine and L-arginine was observed. Since Comparative Example 6 has a larger outer surface area and a lower SAR than Example 34, it is considered that adsorption of basic amino acids to the outer surface acid sites was likely to occur. For non-proteinogenic amino acids, adsorption of 4-aminobutyric acid and ethanolamine was observed for Example 34. Both are primary amines consisting of linear alkyl chains, and considering the minimum diameter of the molecule, they can enter the inside of the zeolite pores, so there is a possibility that they were adsorbed not only on the surface but also inside. Other non-proteinogenic amino acids were hardly adsorbed regardless of molecular size. Both are highly water-soluble compounds, and it is considered that the hydrated state was more stable than in the hydrophobic zeolite pores. In particular, urea is present in large amounts in the digestive tract and has a molecule smaller than the pore size, so there was concern that it would competitively inhibit the adsorption of amines to zeolite, but it was not adsorbed in this study. It can be said that the selectivity of the zeolite used in this study, which is important for its medicinal effect in the body, was confirmed. vitamin The vitamin adsorption test was carried out for each zeolite of Example 34, Example 70, and Comparative Example 6. 3 mg of zeolite was precisely weighed out, and 10 mL of purified water was added. 100 μL of an aqueous solution in which 25 μmol of vitamin was dissolved in 1.0 mL of purified water was added to the zeolite suspension, and the mixture was stirred at room temperature for 1 hour. The solution was centrifuged, and the vitamin concentration of the supernatant was measured by LC-UV (detection wavelength 210 nm), resulting in the results shown in Table 27. The reagents used are shown in Table 28. Note that the adsorption test and analysis were carried out for each vitamin individually, without mixing them. In the case of fat-soluble vitamins (VA, VD3, VE and VK1), the adsorption rate of VK1 was about 50%, but the adsorption rates of VA, VD3 and VE were 15% or less. The molecular size of all fat-soluble vitamins is large, and it is thought that they cannot penetrate into the pores of MFI-type zeolite, so it is thought that this is due to surface adsorption. Since the SAR of Example 34 is higher than that of Comparative Example 6, the fat solubility of the outer surface is higher, and it is thought that the fat solubility of the outer surface of Example 70 is further increased by the amount of surface treatment. It can be seen that the adsorption rate of fat-soluble vitamins is higher, reflecting the fat solubility of these outer surfaces. Of the water-soluble vitamins (VB1, VB3, VB5, VB6, VB12, and VC), VB1, VB5, VB6 (3 types), and VB12 were hardly adsorbed to any of the zeolites (maximum of about 10%). On the other hand, the water-soluble vitamin VC was adsorbed at about 10-30%, and VB3 (2 types) was adsorbed at about 40-60%. It is assumed that VC has many hydroxyl groups and is surface-adsorbed by multipoint hydrogen bonds with the silanols on the outer surface of the zeolite, and the adsorption rate is higher in Comparative Example 6, which has a large outer surface area, than in Example 34, which has a small outer surface area. In addition, since VC is an acidic compound, it is considered that surface adsorption is more likely to occur in Example 70, which has a reduced number of outer surface acid sites by surface treatment, than in Example 34, which still has outer surface acid sites. As for VB3, it has a pyridine structure, which is a tertiary amine, and is thought to be easily stabilized in the zeolite pores having an anionic framework. VB6 also has a pyridine structure, but it has many substituents on the pyridine, and it is thought that due to its size, it did not adsorb into the pores. The other water-soluble vitamins that are difficult to adsorb have a larger molecular size than the water-soluble vitamins that are easily adsorbed, so they cannot penetrate into the pores of the zeolite, and they are highly water-soluble, so they exist stably in a hydrated state. The possibility of using the zeolite in the examples as an adsorbent and remover of heterocyclic amines with a small number of substituents or a small size, such as VB3 (2 types), and as a carrier for sustained-release preparations and controlled-release preparations was demonstrated. Short-chain fatty acids Adsorption tests of short-chain fatty acids were carried out for each of the zeolites of Example 5, Example 34, Example 70, and Comparative Example 6. 3 mg of zeolite was precisely weighed out, and 9.44 mL of purified water was added. 0.143 mL, 0.187 mL, and 0.229 mL of acetic acid, propionic acid, and butyric acid were added, respectively, so that each component was 2.5 μmol. A stir bar was added to this solution and the solution was stirred for 1 hour. After removing the stir bar, the solution was centrifuged. After centrifugation, the solution was diluted 10,000 times with purified water and measured by ion chromatography. The reagents used are shown in Table 29. Short-chain fatty acids were not adsorbed by any of the zeolites. Short-chain fatty acids dissociate in aqueous solution to produce anions of the conjugate base, and are not stabilized by electrostatic interactions with zeolites, which are made of anionic frameworks, and are therefore not adsorbed into the zeolites. Short-chain fatty acids are abundant in the digestive tract of living organisms, and because their molecules are large enough to enter the pores of zeolites, there was concern that they would competitively inhibit the adsorption of amines to zeolites. This study confirmed the selectivity that is important for zeolites to exert their medicinal effects in living organisms. Concomitant medications Adsorption tests were carried out using the zeolites of Examples 34, 70 and 79 for drugs that may be used in combination with the inorganic porous oral composition of this Example (hereinafter referred to as concomitant drugs). 3 mg of zeolite was precisely weighed out and 9.9 mL of purified water was added. 100 μL of a DMSO solution in which 25 μmol of the concomitant drug was dissolved in 1.0 mL of DMSO was added to the zeolite suspension and stirred at room temperature for 1 hour. This liquid was centrifuged, and the concomitant drug concentration in the supernatant was measured by LC-MS / MS, and the adsorption rate (the concomitant drug concentration in the supernatant divided by the initial concentration of 250 μmol / L was subtracted from 1 and expressed as a percentage. In addition, negative values ​​were expressed as 0) was calculated, and the results were as shown in Table 30. The reagents used are shown in Table 31. For carvedilol and miconazole, the solubility of basic compounds, carvedilol and miconazole, was increased by suspending the zeolite in purified water and then adding 10 μL of 1N hydrochloric acid (the pH of the solution immediately after adding the DMSO solution of the concomitant drug was 6-7). Note that the adsorption tests and analysis were performed for each concomitant drug individually, without mixing them. As a result, almost no acidic compounds were adsorbed (adsorption rate <4%). It is known that p-xylene is adsorbed by MFI zeolite, but even acetaminophen and actarit, which have a similar p-substituted benzene structure and are therefore adsorbable due to their molecular size, were hardly adsorbed from water. It is thought that for the same reason as short-chain fatty acids, internal adsorption of acidic compounds into zeolite was unfavorable. Neutral compounds such as pirfenidone and chloramphenicol were not adsorbed at all, and the adsorption rate of lactulose was also low. Neutral compounds do not have electrostatic interactions with surface acid sites, so adsorption is less likely to occur compared to basic compounds. Since lactulose has many hydroxyl groups, it is possible that it was adsorbed to the surface, albeit weakly, by multiple hydrogen bonds with the silanols on the outer surface of the zeolite. Weak adsorption was confirmed for some basic compounds. Metformin is a basic compound with a small molecular size, so it is believed that some of it was adsorbed within the zeolite. At this time, the metformin adsorption rate was lower in the surface-treated Examples 72 and 80 than in the non-surface-treated Example 34. It is believed that the surface treatment partially prevented the adsorption of metformin to the acid sites on the outer surface. As for the other concomitant drugs (mirtazapine, ondansetron, lincomycin, oseltamivir, carvedilol) for which weak adsorption was confirmed, it is believed that the molecular size exceeds the pore size of the MFI zeolite, and therefore this is due to surface adsorption rather than internal adsorption. TMA Precursor Adsorption tests of TMA precursors were carried out for each of the zeolites of Example 34, Example 70, and Comparative Example 6. 3 mg of zeolite was precisely weighed out, and 10 mL of purified water was added. 100 μL of an aqueous solution in which 25 μmol of betaine (trimethylglycine) or carnitine was dissolved in 1.0 mL of purified water was added to the zeolite suspension, and the mixture was stirred at room temperature for 1 hour. The solution was centrifuged, and the betaine or carnitine concentration in the supernatant was measured using an LC-CAD (Charged Aerosol Detector), resulting in the results shown in Table 32. Betaine was adsorbed by all zeolites, but carnitine was not adsorbed in Example 34. Betaine has almost the same molecular size as choline, and it is considered that internal adsorption occurs. On the other hand, carnitine has a larger molecular size than betaine and choline, and it is considered that internal adsorption does not occur easily. In Comparative Example 6, the amount of betaine and carnitine adsorbed was larger than in Examples 34 and 70. Comparative Example 6 has a larger external surface area and a lower SAR than Examples 34 and 70, and therefore it is considered that basic substances are more likely to be adsorbed to the external surface. The reagents used are shown in Table 33. Betaine and carnitine, like choline, are TMA precursors and are also known as nutrients. They are decomposed by bacteria in the digestive tract to produce TMA, so adsorption and release of these TMA precursors affects the amount of TMA absorbed. As with choline, there is a concern that zeolite may act as a delivery agent for these TMA precursors to the large intestine, so it is desirable not to adsorb them. In this test, it was confirmed that the adsorption of betaine and carnitine was weak for Examples 34 and 70. Since the test was not performed in the presence of TMA as in the in vitro adsorption test, it is thought that if the adsorption test was performed in the presence of TMA, competition would occur and the adsorption rate of betaine and carnitine would be lower. Incidentally, TMAO, which is also known as a TMA precursor, does not have a basic structure like betaine and carnitine and is highly hydrophilic, so it was assumed that it would not be adsorbed onto zeolite in water, and therefore no adsorption tests were performed. Serotonin A serotonin adsorption test was carried out for each of the zeolites of Example 34, Example 70, and Comparative Example 6. 3 mg of zeolite was precisely weighed out, and 10 mL of purified water was added. 100 μL of an aqueous solution in which 25 μmol of serotonin (5-hydroxytryptamin, Fujifilm Wako Pure Chemical Industries, Ltd.) was dissolved in 1.0 mL of purified water was added to the zeolite suspension, and the mixture was stirred at room temperature for 1 hour. The solution was centrifuged, and the serotonin concentration of the supernatant was measured by LC-CAD, resulting in the results shown in Table 34. A small amount of adsorption was observed only in Comparative Example 6. It is considered that serotonin was adsorbed on the surface of Comparative Example 6, which has a large external surface area. Serotonin is a physiologically active substance present in the digestive tract, and there is concern that adsorption of serotonin may affect digestive tract motility and other biological reactions related to serotonin, but this test suggested that almost no adsorption was observed on MFI zeolite. Reference example The methods for obtaining and synthesizing the zeolites used in the examples and comparative examples and the methods for measuring the physical properties of the zeolites will be described below. [Examples 1 to 3, Comparative Examples 1 to 14] Table 35 shows the origin of the compounds in Examples 1 to 3 and Comparative Examples 1 to 14. For Examples 1, 3, and Comparative Examples 1 to 14, commercially available products were purchased and used as they were. For Example 2, the purchased zeolite was converted from the ammonia type to the proton type by calcining it under air flow at 500°C for 4 hours. The items in Table 35 indicate the following: Skeleton code: This is the skeleton code of the zeolite used in this example, and conforms to the code that specifies the skeleton structure of zeolite defined by IZA (International Zeolite Association) Counter cation: Counter cation of the zeolite used in this example SAR: The molar ratio of SiO2 to Al2O3 in the zeolite used in this example Product name (product code): Product name of the compound used in this example. The product code is in parentheses. Seller: Seller of the compounds used in this example [Synthesis method of Comparative Example 15] [Hydrothermal synthesis and calcination of organic structure directing agent] The container was charged with 4.5 g of sodium hydroxide (NaOH) granules, 3.8 g of potassium hydroxide (KOH) granules, 66.6 g of 25% by mass N,N,N-trimethyl-1-adamantylammonium hydroxide (TMAdaOH) aqueous solution (Organic Structure Directing Agent; hereafter referred to as OSDA) manufactured by Seichem, 195 g of demineralized water, 7.1 g of Kyoward 200S (alumina content 53.5% by mass) manufactured by Kyowa Chemical Industry Co., Ltd. as aluminum hydroxide, and 225 g of colloidal silica "Cataloid SI-30" manufactured by JGC Catalysts and Chemicals Co., Ltd. as silica, in that order. The composition and molar ratio of the mixture obtained was SiO2:Al2O3:NaOH:KOH:TMAdaOH:H2O=1.0:0.033:0.1:0.06:0.07:20. After thoroughly mixing these raw materials, the resulting mixture was placed in a pressure vessel and subjected to hydrothermal synthesis at 160°C for 48 hours under rotation conditions of 100 rpm, and the resulting gel was filtered by suction and washed with desalted water, and then dried by heating at 100°C for 8 hours or more (hereinafter, the drying operation was performed under these conditions unless otherwise specified). The resulting powder was calcined in air flow at 550°C for 6 hours to remove the OSDA from the powder. [Ion exchange / calcination] The powder from which OSDA had been removed was dispersed at 10% by mass in a 1 mol / L aqueous solution of ammonium nitrate prepared from ammonium nitrate and demineralized water, and subjected to ammonium ion exchange at 80°C for 2 hours, followed by suction filtration and washing with demineralized water. The ion exchange and washing were then repeated two more times. The ion-exchanged powder was then dried and calcined at 500°C for 4 hours under air flow to obtain a proton-type zeolite. [Synthesis method of Comparative Example 16] Into a container, 1.0 g of sodium hydroxide granules, 8.7 g of 18% by mass 1,1'-(1,4-butanediyl)bis(1-azonia-4-azabicyclo[2.2.2]octane) dihydroxide (Dab-4) aqueous solution manufactured by Seichem as OSDA, 8 g of demineralized water, 0.94 g of "Kyoward 200S" as aluminum hydroxide, 7.5 g of "Snowtex 40" as silica, and 0.15 g of CHA-type zeolite synthesized in Comparative Example 15 as seed crystals were sequentially added. The composition and molar ratio of the resulting mixture were SiO2:Al2O3:NaOH:Dab-4:H2O=1.0:0.1:0.5:0.1:22. After thoroughly mixing these raw materials, the resulting mixture was placed in a pressure-resistant container and subjected to hydrothermal synthesis in a 140°C oven for 120 hours under stationary conditions, and the resulting gel was filtered by suction, washed with demineralized water, and then dried. The obtained powder was calcined in an air stream at 550° C. for 6 hours to remove OSDA from the powder. The procedure of [ion exchange and calcination] in Comparative Example 15 was then repeated to obtain a proton-type zeolite. [Synthesis method of Comparative Example 17] 0.772 g of sodium hydroxide granules, 2.262 g of 35% by mass N,N-dimethyl-3,5-dimethylpiperidinium hydroxide (DMDMPIOH) aqueous solution manufactured by Seichem as OSDA, 9.9 g of demineralized water, 0.726 g of "Kyoward 200S" as aluminum hydroxide, 7.454 g of "Snowtex 40" as silica, and 0.300 g of CHA-type zeolite synthesized in Comparative Example 15 as seed crystals were sequentially added to the container. The composition and molar ratio of the resulting mixture were SiO2:Al2O3:NaOH:DMDMPIOH:H2O=1.0:0.013:0.4:0.1:17.5. After mixing these raw materials well, the resulting mixture was placed in a pressure-resistant container and subjected to hydrothermal synthesis in an oven at 180 ° C. for 24 hours under a rotation condition of 15 rpm, and the resulting gel was filtered by suction and washed with demineralized water, and then dried. The obtained powder was calcined in an air stream at 600° C. for 6 hours to remove OSDA from the powder. The procedure of [ion exchange and calcination] in Comparative Example 15 was then repeated to obtain a proton-type zeolite. [Synthesis method of Comparative Example 18] 1.135 g of sodium hydroxide granules, 4.959 g of hexamethyleneimine (HMI) manufactured by Tokyo Chemical Industry Co., Ltd. as OSDA, 63.2 g of demineralized water, 0.944 g of "Kyoward 200S" as aluminum hydroxide, and 14.908 g of "Snowtex 40" as silica were sequentially added to the container. The composition and molar ratio of the obtained mixture were SiO2:Al2O3:NaOH:HMI:H2O=1.0:0.033:0.3:0.5:40. After mixing these raw materials thoroughly, the obtained mixture was placed in a pressure-resistant container and subjected to hydrothermal synthesis in an oven at 150°C under stationary conditions for 144 hours, and the obtained gel was suction filtered and washed with demineralized water and then dried. The obtained powder was calcined at 550°C for 6 hours under air flow to remove OSDA from the powder. Furthermore, the operation of [ion exchange and calcination] of Comparative Example 15 was performed to obtain a proton-type zeolite. [Synthesis method of Comparative Example 19] In Comparative Example 19, zeolite was synthesized in the same manner as in the synthesis method of Comparative Example 18, except that the composition and molar ratio of the raw material mixture was changed to SiO2:Al2O3:NaOH:HMI:H2O = 1.0:0.02:0.3:0.5:40. [Synthesis method of Comparative Example 20] Into the vessel, 7.750 g of 1 mol / L sodium hydroxide solution, 6.487 g of 40 mass% tetrabutylammonium hydroxide (TBAOH) solution manufactured by Tokyo Chemical Industry Co., Ltd. as OSDA, 15.9 g of demineralized water, 0.629 g of "Kyoward 200S" as aluminum hydroxide, and 14.908 g of "Snowtex 40" as silica were sequentially added. The composition and molar ratio of the obtained mixture was SiO ２ The composition was Al2O3:NaOH:TBAOH:H2O=1.0:0.033:0.1:0.1:20. After mixing these raw materials thoroughly, the resulting mixture was placed in a pressure vessel and subjected to hydrothermal synthesis for 72 hours in an oven at 175°C under a rotation condition of 15 rpm, and the resulting gel was suction filtered, washed with desalted water, and then dried. The resulting powder was calcined at 550°C for 6 hours under air flow to remove OSDA from the powder. Furthermore, the operation of [ion exchange and calcination] in Comparative Example 15 was performed to obtain a proton-type zeolite. [Synthesis method of Comparative Example 21] In Comparative Example 21, zeolite was synthesized in the same manner as in Comparative Example 20, except that the composition and molar ratio of the raw material mixture was changed to SiO2:Al2O3:NaOH:TBAOH:H2O = 1.0:0.02:0.1:0.1:20. [Comparative Examples 15 to 21] The framework codes and SARs of the zeolites of Comparative Examples 15 to 21 are summarized in Table 36. The zeolite frameworks were identified by checking the XRPD diffraction patterns. The counter cation of each zeolite is a proton. [Synthesis methods of Examples 4 to 64 and Comparative Example 22] In Examples 4 to 34, Examples 37 to 64, and Comparative Example 22, zeolites were synthesized in the same manner as described below, except that the raw materials used, the amounts charged, the hydrothermal synthesis conditions, the stirring method, and the post-treatment were changed as shown in Tables 37-1, 37-2, and 37-3. All of the zeolites showed the diffraction pattern of MFI zeolite in XRPD. A 1 mol / L sodium hydroxide aqueous solution, 0 to 2 types of Structure Directing Agent (SDA), demineralized water, an aluminum (Al) source, a silicon (Si) source, and seed crystals were added to the container in that order. After thoroughly mixing these raw materials, the resulting mixture was placed in a pressure-resistant container and hydrothermal synthesis was carried out. The resulting gel was then suction filtered, thoroughly washed with demineralized water, and dried by heating at 100°C in an air atmosphere for 8 hours or more. The resulting zeolite powder was then subjected to post-treatment. The items in Tables 37-1, 37-2, and 37-3 indicate the following: Si source: type of Si source added in this example Amount of Si: Amount of Si in the Si source added in this example (unit: mol) Al source: The type of Al source added in this example Charged SAR: The molar ratio of SiO2 to Al2O3 contained in the raw material mixture other than the seed crystals added in this example. If Al2O3 is not included, it is expressed as "∞". Amount of Na: The molar ratio of Na derived from the Si source and NaOH to Si contained in the raw material mixture other than the seed crystals added in this example. SDA1: The first type of SDA added in this example Amount of SDA1: The molar ratio of SDA1 to Si contained in the raw material mixture other than the seed crystal added in this example SDA2: The second type of SDA added in this example Amount of SDA2: The molar ratio of SDA2 to Si contained in the raw material mixture other than the seed crystal added in this example Amount of HO: The molar ratio of HO to Si contained in the raw material mixture other than the seed crystal added in this example Seed crystal: The structure of the seed crystal zeolite added in this example Seed crystal SAR: The molar ratio of SiO2 to Al2O3 of the seed crystal zeolite added in this example Amount of seed crystals: The ratio (mass%) of the amount of seed crystals added to the amount of Si contained in the raw material mixture other than the seed crystals added in this example, converted to SiO. Hydrothermal synthesis temperature: the temperature at which the hydrothermal synthesis was carried out in this example (unit: ° C.) Hydrothermal synthesis time: the time during which the hydrothermal synthesis was carried out in this example (unit: hour) Stirring speed: Stirring speed at which hydrothermal synthesis was carried out in this example (unit: rpm; 0 means stationary conditions) Container: Capacity of the pressure-resistant container in which the hydrothermal synthesis was carried out in this example (unit: L) Post-treatment: Post-treatment method carried out on the zeolite powder obtained by hydrothermal synthesis in this example. The following combinations of [SDA removal], [ion exchange / calcination] and [acid treatment] were carried out in the order listed in the table. [SDA removal] The obtained zeolite powder was calcined in an air stream at 550° C. for 6 hours to remove SDA from the powder. [Ion exchange / calcination] Zeolite powder was dispersed at 10% by mass in a 1 mol / L ammonium nitrate aqueous solution prepared using ammonium nitrate and demineralized water, and ammonium ion-exchange was performed at 80°C for 2 hours, followed by suction filtration and washing with demineralized water. The ion-exchange and washing were then repeated two more times. The ion-exchanged powder was then dried and calcined at 500°C for 4 hours under air flow to obtain proton-type zeolite. [Acid treatment] The obtained zeolite powder was added at 10% by mass to a 1 mol / L aqueous nitric acid solution and stirred at room temperature for 1 hour, filtered by suction, washed with desalted water, and then dried to obtain a proton-type zeolite powder. [Reagents used in the synthesis examples] The reagents used in the synthesis examples of Examples 4 to 35, Examples 37 to 64, and Comparative Examples 15 to 22 are summarized in Table 38. Acid Treatment In Examples 65 to 67, the zeolite was treated with acid using the nitric acid and at the temperature shown in Table 39 under the reaction conditions shown below. [Reaction conditions] To 100 mg of the zeolite of Example 50, which was precisely weighed, 5 mL of 1 mol / L nitric acid aqueous solution (1 mol / L nitric acid (1N)) or concentrated nitric acid (nitric acid 1.38) manufactured by Kanto Chemical was added. The reaction solution was stirred for 5 hours at room temperature or 100°C using a stirrer, and then the zeolite was filtered using a Kiriyama funnel. The filtered product was washed with purified water and dried under reduced pressure at 40°C for 2 hours. In Example 68, the zeolite was treated with acid under the following reaction conditions. [Reaction conditions] To 1 g of the zeolite of Example 48, which was precisely weighed, 10 g of 1 mol / L nitric acid aqueous solution manufactured by Kishida Chemical was added. After stirring the reaction solution at room temperature for 1 hour using a stirrer, the zeolite was filtered using a Kiriyama funnel. The filtered product was washed with desalted water and dried at 100°C in an air atmosphere for 12 hours. In Example 69, the acid treatment of zeolite was carried out in the same manner as in Example 68, except that the reaction time was changed to 2 hours. Surface Treatment In Comparative Example 23 and Examples 70, 72 to 88, surface-treated zeolite was synthesized under any of the reaction conditions shown below using the raw zeolite and surface treatment reagents shown in Table 40. The surface treatment reagents used in the reaction are shown in Table 41. [Reaction conditions: neat (HMDS)] HMDS was added to a precisely measured amount of raw zeolite in a weight ratio of 10 g-HMDS / g-zeolite. The reaction solution was heated to 100°C in an oil bath and stirred under a nitrogen stream for 5 hours. The resulting powder was filtered using a Kiriyama funnel. The filtered product was washed with acetone, air-dried in the air for 8 hours or more, and then dried by heating at 100°C in an air atmosphere for 8 hours or more. [Reaction conditions: toluene-1] Toluene was added to the raw zeolite, 20 mL / g-zeolite. The surface treatment reagent was added at an equivalent ratio of 0.5 mmol / g-zeolite, and the mixture was stirred at room temperature for 5 hours. The powder obtained was filtered using a Kiriyama funnel. The filtered product was washed with ethanol and dried under reduced pressure at 40°C overnight. [Reaction conditions: vapor] A glass bottle containing 100 mg of raw zeolite, an Eppendorf tube containing two drops of purified water, and an Eppendorf tube containing two drops of the surface treatment reagent were placed in a sealable container. The container was sealed and placed in a cabinet heated to 100°C for 5 hours. The zeolite was then dried under reduced pressure at 40°C for 2 hours. [Reaction conditions: neat] A precisely weighed amount of raw zeolite was placed in a thermohygrostat and allowed to absorb moisture overnight under conditions of 25°C / 75% RH. 20 mL / g-zeolite of surface treatment reagent was added, and the mixture was stirred at room temperature for 5 hours. The resulting powder was filtered using a Kiriyama funnel. The filtered product was washed with ethanol and dried under reduced pressure at 40°C for 2 hours. [Reaction conditions: toluene-2] Toluene (7 mL) was added to 100 mg of precisely weighed raw zeolite. Two drops of surface treatment reagent were added, and the mixture was stirred at room temperature for 5 hours. The powder obtained was filtered using a Kiriyama funnel. The filtered product was washed with ethanol and dried under reduced pressure at 40°C for 2 hours. Cation Exchange In Examples 36, 71 and 89, counter cation exchange was carried out under the reaction conditions shown below using a 1 mol / L aqueous nitrate solution prepared from the reagents corresponding to Table 42 and demineralized water. [Reaction conditions] The zeolite of Example 34 was dispersed in 1 mol / L ammonium nitrate aqueous solution at 10% by mass, and ammonium ion-exchanged at 80°C for 2 hours, suction filtered, and washed with desalted water. The ion-exchange, filtration, and washing were then repeated twice. The resulting powder was dried to obtain an ammonia-type zeolite (Example 89). The zeolite of Example 89 was dispersed in 10% by mass in a 1 mol / L lithium nitrate or potassium nitrate aqueous solution, and cation exchange was performed at 80°C for 2 hours, followed by suction filtration and washing with desalted water. The cation exchange, filtration and washing were then repeated two more times. The resulting powder was dried to obtain lithium or potassium type zeolite (Examples 36 and 71). <Measurement of physical properties> Measurement method Zeolite composition analysis Elemental analysis of silicon atoms, aluminum atoms, and sodium atoms in the zeolite standard sample was carried out as follows. The precisely weighed sample was added with an alkali salt melt and heated to melt, then dissolved in warm water and appropriately diluted with a solution containing added acid, and the silicon atom, aluminum atom and sodium atom contents (wt%) were determined by the acid concentration matching calibration curve method using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Furthermore, the fluorescent X-ray intensity of the analyzed elements in the zeolite standard sample was determined, and a calibration curve was created with the atomic concentration determined by ICP-AES. The contents (wt%) of silicon atoms, aluminum atoms, and sodium atoms in the zeolite samples were determined by ICP-AES or X-ray fluorescence analysis using a calibration curve with ICP-AES. For samples with a low aluminum content, hydrofluoric acid was added to a precisely weighed sample and heated to volatilize and remove the silicon, and the remaining ash was dissolved in acid, and the aluminum atom content (wt%) was determined by the acid concentration matching calibration curve method with ICP-AES. ICP-AES was performed using an ULTIMA 2C manufactured by Horiba, Ltd. X-ray fluorescence analysis was performed using a Supermini200 manufactured by Rigaku. Powder X-ray diffraction measurement Measurements and data analysis were performed using a powder X-ray diffraction measurement device X'PertPro (PANalytical B.V.) under the following conditions. [Measurement conditions] X-ray generator: X-ray tube (anticathode: copper, tube voltage: 45 kV, tube current: 40 mA) Incident optical system: focusing mirror Receiving optical system: High-speed semiconductor array detector (X-Celerator), extended receiving arm Sample stage: HTS sample stage (oscillates in the X-axis direction with a width of 4 mm) Number of measurements: 5 (angle of incidence changed to -2, -1, 0, 1 and 2°) Measurement range: 2θ=3 to 40° Scan speed: 0.668451° / sec Step: 0.0167° [Analysis method] Software: High Score Plus Peak Search Minimum significance: 1.00 Min Peak Tip (°2Th.): 0.01 Maximum peak tip (°2Th.): 1.00 Peak base width (°2Th.): 2.00 <Profile fit> Run Default Profile Fit three times BET specific surface area and external surface area measurement (Pretreatment) Prior to the measurement of the surface area, 30 to 80 mg of zeolite powder was loaded into the measurement cell as a pretreatment, and a heating and degassing treatment was carried out at 350°C under reduced pressure for 5 hours using a pretreatment device (Quantachrome MasterPrep). (Measurement of adsorption amount) The adsorption isotherm of the pretreated zeolite powder was measured. The measurement was performed using a constant volume gas adsorption measuring device (Autosorb iQ-XR-XR-XR or Autosorb iQ3-MP-XR manufactured by Quantachrome). The adsorbate was nitrogen, and the relative pressure was 1×10 at liquid nitrogen temperature. -5 Adsorption isotherms were measured in the range of 0.995 to 0.995. A BET plot was created from the obtained adsorption isotherms, and a BET multipoint analysis was performed in the range with good linearity to determine the BET specific surface area. Furthermore, a t-plot (standard isotherm: de-Bore equation) was created, and the external surface area was calculated from the slope and intercept of the plateau part. SEM Platinum was deposited on the surface of the zeolite sample to a thickness of approximately 9 nm using an Ion Coater IB-3 manufactured by Eiko Co., Ltd., and the shape was then observed using a scanning electron microscope S-4500 manufactured by Hitachi High-Tech Corporation or a JEOL JSM-6010LV. Particle size distribution The particle size distribution was measured using a laser diffraction / scattering particle size distribution analyzer LA-950V2 manufactured by Horiba, Ltd. The measurement was performed in a flow cell with pure water as the dispersion medium, the refractive index of the sample set to 1.450-0.000i, the refractive index of the dispersion medium set to 1.333-0.000i, the circulation speed range set to 5, and the stirring speed range set to 2.

Claims

1. An oral composition comprising an inorganic porous material, wherein when choline and primary, secondary, or tertiary amine or ammonia are present as a mixture in equimolar amounts in artificial intestinal fluid, and 11.8 g of said inorganic porous material per 1 mmol of choline is mixed at a concentration of 2 g / L for 1 hour, the adsorption rate of primary, secondary, or tertiary amine or ammonia is 60.0% or more and the adsorption rate of choline is 40.0% or less.

2. The oral composition according to claim 1, wherein the inorganic porous material has an adsorption rate for primary, secondary, or tertiary amines or ammonia that is 2.00 times or more higher than the adsorption rate for choline.

3. The oral composition according to claim 1, wherein the inorganic porous material is an aluminosilicate or silicate.

4. The oral composition of claim 3, wherein the aluminosilicate is a zeolite.

5. The composition for oral administration according to claim 4, wherein the maximum number of ring members of the zeolite is 10 and the maximum spherical diameter of diffusion within the pores is 3.68 Å or more.

6. The oral composition according to claim 4, wherein the zeolite is of MFI or FER structure.

7. The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to claim 4, wherein the zeolite has a molar ratio of from 15.0 to 130,000.

0.

8. The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to claim 7, wherein the zeolite has a molar ratio of from 30.0 to 80.

0.

9. The zeolite has an external surface area of ​​33.0 m ２ The composition for oral administration according to claim 4, wherein the molecular weight of the composition is 1000 or less.

10. The oral composition of claim 1, which is a pharmaceutical composition.

11. The oral composition according to claim 10, which is used for the prevention, treatment or alleviation of symptoms of a disease caused by primary, secondary or tertiary amines, ammonia or their metabolites.

12. The oral composition according to claim 11, wherein the primary, secondary, or tertiary amine, ammonia, or a metabolite thereof includes one or more members selected from the group consisting of trimethylamine, dimethylamine, methylamine, histamine, ammonia, and trimethylamine-N-oxide.

13. The oral composition according to claim 11, wherein the primary, secondary, or tertiary amine, ammonia, or a metabolite thereof is trimethylamine or trimethylamine-N-oxide.

14. The oral composition according to claim 11, wherein the disease caused by a primary, secondary or tertiary amine, ammonia or a metabolite thereof is selected from the group consisting of trimethylaminuria, cardiovascular disease, glaucoma, atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, colorectal cancer, irritable bowel syndrome, hyperammonemia, urea cycle disorders, organic acidemia, hepatic encephalopathy, and portosystemic shunt.

15. The oral composition according to claim 14, wherein the disease is a disease caused by trimethylamine, and the disease is trimethylaminuria, cardiovascular disease, or glaucoma.

16. The oral composition according to claim 14, wherein the disease is a disease caused by trimethylamine-N-oxide, and the disease is atherosclerosis, coronary heart disease, heart failure with preserved ejection fraction, ST-segment elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's dementia, obesity, advanced chronic kidney disease in patients with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, or colorectal cancer.

17. The oral composition according to claim 14, wherein the disease is a disease caused by histamine, and the disease is irritable bowel syndrome.

18. The oral composition according to claim 14, wherein the disease is an ammonia-induced disease, and the disease is hyperammonemia, urea cycle disorder, organic acidemia, hepatic encephalopathy, or portosystemic shunt.

19. The oral composition according to claim 10, which contains zeolite as an active ingredient, is administered 1 to 5 times a day, and the dosage of said zeolite is 200 mg to 42,000 mg per dose.

20. The oral composition according to claim 19, wherein the dosage of the zeolite is 500 mg to 2000 mg per dose.

21. A method for producing the oral composition of claim 4, comprising obtaining the zeolite by hydrothermal synthesis without the use of an organic structure directing agent.

22. The method according to claim 21, wherein sodium carbonate or sodium sulfate is used as the raw material.

23. The method of claim 21, comprising converting to the proton form with an acid.

24. The method of claim 23, wherein the acid is sulfuric acid or nitric acid.

25. The method according to claim 21, further comprising subjecting the zeolite after hydrothermal synthesis to a surface treatment in a solution containing a Si element source.

26. A method for producing a zeolite-containing zeolite, the zeolite having an MFI structure and Al ２ O ３ SiO ２ or the zeolite has an FER structure and has a molar ratio of Al ２ O ３ SiO ２ 1. A composition for oral administration, which is used for treating, preventing or alleviating symptoms of a disease selected from the group consisting of trimethylaminuria, atherosclerosis, irritable bowel syndrome and hyperammonemia, wherein the molar ratio of 27. The zeolite is Al ２ O ３ SiO ２ The composition for oral administration according to claim 26, wherein the zeolite has a molar ratio of from 30.0 to 80.

0.

28. Zeolite has an external surface area of ​​33.0 m ２ 27. The oral composition of claim 26, wherein the molecular weight is less than 1.0 g.

29. The oral composition of claim 26, which is a pharmaceutical composition.

30. The oral composition of claim 29, which is administered 1 to 5 times a day, with the dosage of said zeolite being 200 mg to 42,000 mg per dose.

31. The oral composition according to claim 30, wherein the amount of zeolite administered is 500 mg to 2000 mg per dose.

32. A method for producing the oral composition according to claim 26, in which the zeolite is obtained by hydrothermal synthesis without the use of an organic structure directing agent.

33. The method according to claim 32, wherein sodium carbonate or sodium sulfate is used as a raw material.

34. The method of claim 32, comprising converting to the proton form with an acid.

35. The method of claim 34, wherein the acid is sulfuric acid or nitric acid.

36. The method according to claim 32, further comprising subjecting the zeolite after hydrothermal synthesis to a surface treatment in a solution containing a Si element source.