Search

EP-4736861-A1 - ORAL COMPOSITION CONTAINING INORGANIC POROUS BODY

EP4736861A1EP 4736861 A1EP4736861 A1EP 4736861A1EP-4736861-A1

Abstract

The oral composition of the present disclosure includes an inorganic porous material, and with respect to choline and a primary, secondary, or tertiary amine or ammonia present as an equimolar mixture in simulated intestinal fluid, when 11.8 g of the inorganic porous material per 1 mmol of choline is mixed at a concentration of 2 g/L for 1 hour, the adsorption ratio of the primary, secondary, or tertiary amine or ammonia is 60.0% or more, and the adsorption ratio of choline is 40.0% or less. Alternatively, the oral composition of the present disclosure includes a zeolite, wherein the zeolite has an MFI structure and a molar ratio of SiO 2 to Al 2 O 3 of 30.0 or more and 130,000.0 or less, or the zeolite has a FER structure and a molar ratio of SiO 2 to Al 2 O 3 of 15.0 or more and 130,000.0 or less.

Inventors

  • KOHYAMA, Yuh
  • MATSUMOTO, TAKUMI
  • KODAIRA, Ayako
  • TOGO, Yuka
  • HIKIMA, Shu
  • OHNISHI, Ryohji
  • TAKEWAKI, TAKAHIKO
  • KATAGIRI, NORIKO

Assignees

  • Tanabe Pharma Corporation
  • Mitsubishi Chemical Corporation

Dates

Publication Date
20260506
Application Date
20240626

Claims (20)

  1. An oral composition comprising; an inorganic porous material, wherein the oral composition has an adsorption ratio of primary, secondary, or tertiary amine or ammonia of 60.0% or more, and has an adsorption ratio of choline of 40.0% or less, when each adsorption ratio is measured by the following method: to simulated intestinal fluid in which choline and the primary, secondary, or tertiary amine or ammonia are present as an equimolar mixture, the inorganic porous material is added at a concentration of 2 g/L in an amount of 11.8 g of the inorganic porous material per 1 mmol of choline, and after mixing them for 1 hour, each the adsorption ratio is measured.
  2. The oral composition according to claim 1, wherein the adsorption ratio of the primary, secondary, or tertiary amine or ammonia to the inorganic porous material is 2.00 times or more than the adsorption ratio of choline.
  3. The oral composition according to claim 1, wherein the inorganic porous material is an aluminosilicate or a silicate.
  4. The oral composition according to claim 3, wherein the aluminosilicate is a zeolite.
  5. The oral composition according to claim 4, wherein the zeolite has a maximum ring number of 10 and a largest free sphere diameter of 3.68 Å or more.
  6. The oral composition according to claim 4, wherein the zeolite has an MFI structure or a FER structure.
  7. The oral composition according to claim 4, wherein the zeolite has a molar ratio of SiO 2 to Al 2 O 3 of 15.0 or more and 130,000.0 or less.
  8. The oral composition according to claim 7, wherein the zeolite has a molar ratio of SiO 2 to Al 2 O 3 of 30.0 or more and 80.0 or less.
  9. The oral composition according to claim 4, wherein the external surface area of the zeolite is 33.0 m 2 /g or less.
  10. The oral composition according to claim 1, wherein the oral composition is a pharmaceutical composition.
  11. The oral composition according to claim 10, for use in the prevention, treatment, or alleviation of symptoms of a disease caused by a primary, secondary, or tertiary amine, ammonia, or a metabolite thereof.
  12. The oral composition according to claim 11, wherein the primary, secondary, or tertiary amine, ammonia, or the metabolite comprises one or more 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 the metabolite 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 the metabolite is selected from the group consisting of trimethylaminuria, cardiovascular disease, glaucoma, atherosclerosis, coronary artery heart disease, heart failure with preserved ejection fraction, ST-elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's disease, obesity, progressive 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 disorder, organic acidemia, hepatic encephalopathy, and portosystemic shunt.
  15. The oral composition according to claim 14, wherein the disease is caused by trimethylamine, and the disease is trimethylaminuria, cardiovascular disease, or glaucoma.
  16. The oral composition according to claim 14, wherein the disease is caused by trimethylamine-N-oxide, and the disease is atherosclerosis, coronary artery heart disease, heart failure with preserved ejection fraction, ST-elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's disease, obesity, progressive 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.
  17. The oral composition according to claim 14, wherein the disease is caused by histamine, and the disease is irritable bowel syndrome.
  18. The oral composition according to claim 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 oral composition according to claim 10, wherein the oral composition comprises zeolite as an active ingredient, is administered 1 to 5 times per day, and the dose of the zeolite is 200 mg to 42,000 mg per administration.
  20. The oral composition according to claim 19, wherein the dose of the zeolite is 500 mg to 2000 mg per administration.

Description

TECHNICAL FIELD The present disclosure relates to an oral composition containing an inorganic porous material, which is formulated to selectively adsorb primary, secondary, or tertiary amines or ammonia over choline. BACKGROUND ART Some primary, secondary, and tertiary amines or ammonia exist as toxins in the body, and their excessive presence can cause various diseases. For example, in trimethylaminuria (fish odor syndrome), due to a genetic defect in the trimethylamine-metabolizing enzyme FMO3 (flavin-containing monooxygenase 3) or similar conditions, the concentration of trimethylamine (TMA) in bodily fluids becomes higher than in healthy individuals. The volatile component, trimethylamine, is excreted in sweat, breath, urine, and other bodily fluids, causing a body odor like rotting fish, which diminishes the quality of life and social activities of patients with trimethylaminuria, and can also lead to psychiatric symptoms such as depression. There is no fundamental cure, and symptomatic treatments are mainly performed, such as dietary restrictions of foods rich in trimethylamine precursors like 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 the basic substance trimethylamine. Furthermore, TMAO, a metabolite of trimethylamine, has been reported to be a pathogenic molecule of atherosclerosis. In addition, its involvement has been reported in coronary artery heart disease, heart failure with preserved ejection fraction, ST-elevation myocardial infarction, atrial fibrillation, abdominal aortic aneurysm, ischemic stroke, post-stroke cognitive impairment, mild cognitive impairment, Alzheimer's disease, obesity, progressive chronic kidney disease with type 2 diabetes, cardiovascular complications in chronic kidney disease, diabetic retinopathy, non-alcoholic steatohepatitis, polycystic ovary syndrome, Parkinson's disease, and colorectal cancer. There are also reports that histamine excessively produced by intestinal bacteria increases histamine concentration in the gastrointestinal tract, activating H4 receptors and inducing abdominal pain in patients with irritable bowel syndrome. Moreover, when detoxification of ammonia to urea in the liver becomes insufficient due to liver failure, cirrhosis, portosystemic shunt, urea cycle disorders, organic acidemia, etc., an excess of ammonia in the circulating blood, i.e., hyperammonemia, occurs, leading to hepatic encephalopathy. As in the examples above, it is thought that detoxification of a poisoned state or treatment of a disease can be achieved by adsorbing and removing excess primary, secondary, or tertiary amines or ammonia that act as toxins or pathogenic substances. However, there is a problem of selectivity against choline, which is a basic organic molecule with similar properties and also a nutrient. Choline is an essential nutrient for the body, especially indispensable for growth and development. Choline deficiency has been reported to cause various diseases. Materials (adsorbents) for adsorbing and removing basic compounds from bodily fluids, and more broadly from water, include activated carbon, cation exchange resins, clay minerals, inorganic porous bodies, and metal organic frameworks (MOF). Choline, primary, secondary, tertiary amines, and ammonia are all basic compounds. When they exist as the same cationic species in water, it is difficult to distinguish and selectively adsorb primary, secondary, or tertiary amines or ammonia over choline, and no such adsorbent is known. Patent Document 1 discloses the treatment of trimethylaminuria using zeolite. Some primary, secondary, tertiary amines, ammonia, or their metabolites exist as toxins in the body, and their excessive presence causes various diseases. It is believed that by adsorbing and removing excess primary, secondary, or tertiary amines or ammonia that act as toxins or pathogenic substances, it could be used for the treatment of a poisoned state or disease. However, the simultaneous removal of choline, a molecule with similar properties that is also a nutrient, becomes a problem in terms of the adsorbent's toxicity. Therefore, there is a need to selectively adsorb and remove primary, secondary, or tertiary amines or ammonia over choline. Patent Document 1 does not disclose any specific examples of adsorbing trimethylamine using zeolite, nor does it disclose the selective adsorption of trimethylamine over choline by zeolite or the specific characteristics of zeolite for that purpose, and it does not focus on the aforementioned adsorption selectivity at all. PRIOR ART DOCUMENTS PATENT DOCUMENTS Patent Document 1: U.S. Patent Application Publication No. 2018/0200291 SUMMARY OF INVENTION TECHNICAL PROBLEM The present disclosure has been made in view of the above circumstances, and an object thereof is to provide an oral composition that has good safety and ca