Double salt, preparation method therefor, pharmaceutical composition containing same, and use thereof

Abstract

The present disclosure relates to a double salt, a preparation method therefor, and a pharmaceutical composition containing same. More specifically, the present disclosure relates to a double salt consisting of magnesium ions, monovalent metal cations, phosphate ions, optional hydrogen phosphate ions, and optional hydroxide ions. The present disclosure further relates to a method for preparing the double salt, a pharmaceutical composition containing the double salt, a kit containing the pharmaceutical composition, the use of the double salt in the preparation of a drug for reducing the level of ammonia and / or ammonium ions and / or urea in the blood and / or digestive tract of a subject and preventing and / or treating a disease or condition associated therewith, and a method for preventing and / or treating a related disease or condition.

Description

A complex salt, its preparation method, a pharmaceutical composition comprising the complex salt, and its uses.

[0001] Cross-reference to related applications

[0002] This application claims priority to PCT application No. PCT / CN2024 / 104218, filed on July 8, 2024, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure relates to a complex salt, specifically to a complex salt composed of magnesium ions, a monovalent metal cation, phosphate ions, optionally hydrogen phosphate ions, and optionally hydroxide ions. This disclosure also relates to methods for preparing the complex salt, pharmaceutical compositions comprising the complex salt, pharmaceutical kits comprising the pharmaceutical compositions, and the use of the complex salt in the preparation of medicaments for reducing levels of ammonia and / or ammonium ions and / or urea in the blood and / or digestive tract of a subject, and for the prevention and / or treatment of related diseases or conditions. Background Technology

[0004] Ammonia and urea are both major metabolic byproducts produced during human metabolism. The main sources of ammonia in the blood include ammonia produced from the breakdown of amino acids in various tissues and ammonia absorbed through the intestines. Ammonia is toxic to the body, therefore maintaining appropriate blood ammonia levels is crucial for normal bodily functions. Generally, blood ammonia is mainly converted into non-toxic urea through the urea cycle in the liver and consumed by glutamine synthetase, which converts glutamate and ammonia into glutamine. Hyperammonemia is a clinical syndrome characterized by abnormally high blood ammonia levels and central nervous system dysfunction. Urea is one of the main products of protein metabolism, primarily excreted through the kidneys, with a small portion excreted through the intestines. Excessive urea synthesis or impaired excretion can lead to urea accumulation in the body, causing various diseases. For example, patients with chronic kidney disease, due to decreased kidney function and impaired urea excretion, are prone to azotemia, characterized by elevated blood urea levels. In conclusion, the accumulation of ammonia or urea in the body can trigger a series of health problems. Finding drugs that can effectively lower blood ammonia and urea levels is of significant clinical importance for the prevention and / or treatment of these diseases. Summary of the Invention

[0005] This disclosure generally relates to a complex salt comprising magnesium ions, a monovalent metal cation, phosphate ions, optionally hydrogen phosphate ions, and optionally hydroxide ions. Specifically, in one aspect, this disclosure relates to the complex salt having Formula I. In another aspect, this disclosure relates to a method for preparing the complex salt. In another aspect, this disclosure relates to a pharmaceutical composition comprising the complex salt. In another aspect, this disclosure relates to a pharmaceutical composition comprising the complex salt for treating conditions related to inappropriately elevated ammonia and / or ammonium ion levels in the blood and / or digestive tract of a subject. In another aspect, this disclosure relates to a pharmaceutical composition comprising the complex salt for treating conditions related to inappropriately elevated urea levels in the blood and / or digestive tract of a subject. In another aspect, this disclosure relates to a cassette comprising the pharmaceutical composition. In another aspect, this disclosure relates to a method and related pharmaceutical use of treating conditions related to inappropriately elevated ammonia and / or ammonium ion levels in the blood and / or digestive tract of a subject by administering the complex salt or a pharmaceutical composition comprising the complex salt to a subject in need. On the other hand, this disclosure relates to methods and related pharmaceutical uses for treating conditions associated with inappropriately elevated urea levels in the blood and / or digestive tract of a subject by administering the compound salt or a pharmaceutical composition containing the compound salt to a subject in need of such treatment.

[0006] More specifically, in the first aspect, this disclosure provides a compound of formula I:

[0007] Mg3(PO4 3- ) a M b (HPO4 2- ) c (OH) d

[0008] I

[0009] Where M is selected from alkali metal ions, ammonium ions or any combination thereof; a≥1.5; b>0; c≥0; d≥0; where when a<2, c<0.4.

[0010] In a second aspect, this disclosure provides a method for preparing the compound of formula I, comprising the following steps: mixing phosphoric acid and magnesium phosphate pentahydrate in water and stirring to obtain a mixture A; adding MOH or an aqueous solution thereof to mixture A and stirring to obtain a mixture B; allowing mixture B to stand and age for a period of time to obtain a crude product; washing the crude product with water to remove soluble substances to obtain the compound of formula I, wherein the MOH is an alkali metal hydroxide, ammonium hydroxide, or any combination thereof.

[0011] In a third aspect, this disclosure provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients. In this aspect, this disclosure also provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4). In this respect, the present disclosure also provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with elevated urea levels in the blood of a subject; or (5) two or more of (1) to (4) above.

[0012] In a fourth aspect, this disclosure provides a medicine box comprising: any of the pharmaceutical compositions described herein; at least one container for containing the pharmaceutical composition; and instructions for use and / or a pharmaceutical label.

[0013] In a fifth aspect, this disclosure provides a method for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4) above, the method comprising administering to a subject in need a compound of formula I or a pharmaceutical composition comprising a compound of formula I and optionally one or more pharmaceutically acceptable excipients. In this respect, this disclosure also provides the use of a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients in the preparation of a medicine for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) the use of two or more of the above (1) to (4) in a pharmaceutical medicament.

[0014] In a sixth aspect, this disclosure provides a method for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) two or more of the above (1) to (4), said method comprising administering to a subject in need a compound of formula I or a pharmaceutical composition comprising a compound of formula I and optionally one or more pharmaceutically acceptable excipients. In this respect, this disclosure also provides the use of a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients in the preparation of a pharmaceutical composition for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) the use of two or more of the above (1) to (4) in a pharmaceutical composition.

[0015] The illustrative embodiments of this disclosure are shown and described in detail below, from which other aspects and advantages of this disclosure will become apparent to those skilled in the art. As will be appreciated by those skilled in the art, the appended descriptions are exemplary and not restrictive. Detailed Implementation

[0016] The following discloses various exemplary embodiments or examples of the invention involved in this application. It should be understood that these embodiments or examples are merely illustrative and not intended to limit the scope of protection of the invention involved in this application. Many variations, modifications, and substitutions of these exemplary embodiments or examples will occur to those skilled in the art without departing from the spirit of this disclosure. It should be understood that these embodiments or examples obtained through variations, modifications, or substitutions also fall within the scope of protection of this application.

[0017] Where the specification references publications, patents, or patent applications, all referenced publications, patents, or patent applications are incorporated herein by reference in their entirety, as if each individual publication, patent, or patent application were specifically and individually incorporated herein by reference in its entirety. In the event of any conflict between a publication, patent, or patent application incorporated by reference and the disclosure contained in the specification, the interpretation and / or description in this specification shall prevail.

[0018] Where a range of values ​​is mentioned in the specification, it should be understood that all ranges of values ​​mentioned in this disclosure are intended to explicitly disclose the two endpoints of the range (i.e., the upper and lower limits), all values ​​(especially integers) within the range, and the various subranges formed by these values ​​(especially integers).

[0019] definition

[0020] As used throughout this document, the singular forms “a,” “an,” “the,” and “the” also include plural referents, unless the context clearly indicates otherwise. Furthermore, unless specifically stated that a referent is singular or plural, this application includes both singular and plural referents.

[0021] As used throughout this article, the term "multiple" refers to more than one, including but not limited to two, three, four, five, six, etc.

[0022] As used throughout this document, the terms “comprising,” “including,” “having,” “containing,” and variations thereof are intended to indicate open-ended transitional phrases, terms, or words that do not exclude the possibility of additional steps, substances, or structures. When such terms are used to describe a medicament, cassette, use, or method of this disclosure, they also cover the case where the medicament, cassette, use, or method is composed of the listed elements or components. In the context of this disclosure, the term “composed of” indicates that, in addition to the listed elements or components, the subject matter or method does not contain any unlisted elements or components (e.g., steps, substances, or structures).

[0023] As used throughout this document, the term “optional” means that the element or event described below may exist / occur or may not exist / not occur, and both the existence / occurrence and non-occurrence of the element or event are considered to have been specifically disclosed.

[0024] As used throughout this document, the term "about" means approximately, in the region of, roughly, or around, and is used to indicate that the described feature is within an acceptable margin of error for a person skilled in the art to a given value. When the term "about" is used to refer to a numerical value, it indicates any value within ±20% of the listed value. In some embodiments, the term "about" covers any value within ±10%, ±5%, ±1%, ±0.5%, or ±0.1% of the specific value modified by the term.

[0025] As used throughout this document, the term "mixture" refers to a substance formed by mixing two or more substances in a certain proportion. When a mixture is described in the context of this disclosure as "a mixture of two or more of A, B, C...", "A, B, C... or a mixture thereof", or similar terms, it should be understood that the scope of this disclosure is intended to cover any mixture formed by mixing components A, B, C... in a permutation and combination manner.

[0026] As used throughout this document, the term "drug" refers to a substance that can affect the physiological functions of organs and cellular metabolic activities of a subject, thereby producing beneficial biological effects (including prevention, treatment, and diagnosis of diseases) in the subject. In the context of this disclosure, "drug" may refer only to the active pharmaceutical ingredient (active drug substance), but also includes pharmaceutical compositions (including their formulation forms).

[0027] As used throughout this document, the term "pharmaceutical composition" refers to a substance suitable for administration to a subject for a particular medical purpose, which is a mixture (optionally further processed) of an active pharmaceutical ingredient (e.g., a compound of formula I) and an optional pharmaceutically acceptable excipient in a specified proportion. Pharmaceutical compositions as described in this disclosure can be prepared using procedures well known in the art (see, for example, Ansel, Introduction to Pharmaceutical Dosage Forms, Seventh Edition (1999)). This procedure typically involves the step of mixing the active pharmaceutical ingredient with one or more pharmaceutically acceptable excipients. Generally, pharmaceutical compositions are prepared by uniformly and closely mixing the active pharmaceutical ingredient with one or more pharmaceutically acceptable liquid excipients or one or more pharmaceutically acceptable finely ground solid excipients, or both, and then, if desired, shaping the resulting mixture into the desired form. For example, tablets can be prepared by optionally compressing or molding the active pharmaceutical ingredient with one or more pharmaceutically acceptable excipients.

[0028] As used throughout this article, the terms “preparation,” “pharmaceutical formulation,” and “dosage form” are used interchangeably and refer to a pharmaceutical composition prepared in accordance with certain dosage form requirements to meet the needs of disease prevention, treatment, or diagnosis, and is intended for direct individual use.

[0029] As used throughout this document, the term "unit dosage form" refers to a physically discrete unit that is individually packaged and intended for use by a subject in need, as is known in the art. Each unit dosage form contains a predetermined amount of active pharmaceutical ingredient sufficient to produce the desired preventive and / or therapeutic effect, as well as one or more pharmaceutically acceptable excipients. Examples of unit dosage forms include, but are not limited to, individually packaged tablets or capsules. A unit dosage form may be administered once or multiple times, and in the case of multiple administrations, a portion of it may be given each time. A multi-dose form is multiple identical unit dosage forms packaged in a single package. Examples of multi-dose forms include multiple identical tablets or capsules in bottles. Thus, a multi-dose form is a form in which multiple, unsegregated unit dosage forms are present in a package.

[0030] As used throughout this document, the term "dosage" refers to the amount of active pharmaceutical ingredient used. In the context of this disclosure, unless otherwise stated, dosage is expressed as the mass of the active pharmaceutical ingredient per kg of the subject's body weight per day.

[0031] As used throughout this document, the terms "pharmacy kit" and "reagent kit" are used interchangeably and refer to a pharmaceutical composition contained in a suitable container. The pharmaceutical kit may contain at least one, such as one, two, three, or more containers. Containers used to manufacture pharmaceutical kits are well known in the art and include, but are not limited to, blister packs, tubes, bottles, pumps, bags, tubular vials, syringes, cartons, or other containers. The pharmaceutical kit may contain written materials, i.e., drug instructions and / or drug labels, which may include instructions for use, clinical trial results and discussions of results, a list of side effects, drug interactions, and / or additional information useful to healthcare providers, such as references. This information may be based on various studies, such as those using research involving laboratory animals and those based on human clinical trials. The pharmaceutical kit may also contain other items, such as measuring cups for liquid formulations, foil packaging to minimize air exposure, etc.

[0032] As used throughout this article, the term "pharmaceutically acceptable" means, to the extent of reasonable medical judgment, that a substance is suitable for contact with a subject's tissues or organs without causing excessive toxicity, irritation, allergic reactions or other problems, while having a proportionate and reasonable benefit / risk ratio.

[0033] As used throughout this document, the term "pharmaceuticalally acceptable excipient" means an excipient (or carrier) that will not cause excessive irritation to the tissues or organs of a subject and will not eliminate the pharmacological activity and properties of the administered drug. In the context of this disclosure, the term "pharmaceuticalally acceptable excipient" includes any and all solvents, dispersion media, coating agents, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents, etc.), isotonic agents, absorption delay agents, salts, stabilizers, fillers, binders, disintegrants, lubricants, gliding agents, sweeteners, flavoring agents, dyes, etc., and one or more combinations thereof. Examples of pharmaceutically acceptable excipients that can be used to prepare pharmaceutical compositions as described in this disclosure include, but are not limited to: solvents, such as water, ethanol, glycerol, propylene glycol, DMSO, polyethylene glycol, fatty oils such as sesame oil, corn oil, cottonseed oil, or peanut oil, liquid paraffin, ethyl oleate, or isopropyl myristate; surfactants, such as sulfates, sulfonates, quaternary ammonium compounds, lecithin, Span derivatives, Tween derivatives, polyethylene glycol 40 stearate, phenobarbital O, or poloxamer; emulsifiers, such as gelatin, gum arabic, astragalus gum, bentonite, or surfactants such as polyoxyethylene sorbitan monooleate; suspending agents, such as sodium carboxymethyl cellulose, pectin, astragalus gum, magnesium aluminum silicate, or gum arabic; fillers, such as lactose, sucrose, trehalose, lysine, leucine, kaolin, calcium hydrogen phosphate, mannitol, microcrystalline cellulose, or pregelatinized starch; and binders, such as cellulose, PVP, or dextrin. Disintegrants, such as croscarmellose sodium, glycolic acid starch sodium, alginate, corn starch, potato starch, bentonite, methylcellulose, agar, or hydroxypropyl starch; lubricants, such as talc, polyethylene glycol, calcium stearate, magnesium stearate, zinc stearate, or stearic acid; flow aids, such as colloidal silica; colorants, such as any approved, certified water-soluble or water-insoluble FD and C dyes (e.g., dyes suspended on alumina hydrate); wetting agents, such as propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, or polyoxyethylene lauryl ether; enteric coating agents, such as fatty acids, fats, waxes, shellac, ammoniated shellac, or cellulose acetate; film coating agents, such as hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000, or cellulose acetate; sustained-release agents, such as Eudragit. Polymers such as series and cellulose esters; sweeteners, such as fructose, glucose, sucrose, artificial sweeteners such as sucralose, aspartame or saccharin, agave syrup, maple syrup or corn syrup; flavoring agents, such as natural flavorings extracted from fruits, mint and other plants or methyl salicylate; buffers, such as citrates, phosphates and other organic acids and / or their salts; antioxidants, such as ascorbic acid, methionine, citric acid, D,L-α-tocopherol, BHA, BHT, monothioglycerol, ascorbyl palmitate, ascorbic acid or propyl gallate; preservatives, such as benzoic acid, sodium benzoate, parabens such as methylparaben or propylparaben, sorbic acid or benzalkonium bromide; pH adjusters, such as citric acid, sodium citrate, hydrochloric acid, NaOH or other weak acids or weak bases; chelating agents or other materials capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA) or its salts. Examples of suitable pharmaceutically acceptable excipients can be found, for example, in Remington's Pharmaceutical Sciences, 18th edition, Mack Printing Company, 1990, pp. 1289-1329, which is hereby incorporated by reference. The use of any conventional excipient in this disclosure will be considered unless it is incompatible with the active ingredient.

[0034] As used throughout this article, the terms "crystallization form," "crystal form," and "crystal" are used interchangeably to refer to the process in which the microscopic units constituting a substance, such as atoms, ions, or molecules, are arranged in space according to a certain periodicity to form a solid with a regular geometric shape. Depending on the different periodic spatial arrangements of atoms, ions, or molecules, a substance can exist in two or more different crystallization forms.

[0035] As used throughout this article, the term "amorphous matter" or "amorphous" refers to a solid in which the microscopic units constituting matter, such as atoms, ions, or molecules, are not arranged periodically in a certain spatial order (i.e., exhibiting a disordered distribution), in contrast to crystals.

[0036] As used throughout this document, the term "aqueous solution of mixed inorganic salts" refers to an aqueous solution containing alkali metal halides in addition to ammonia and / or ammonium ions. Of course, to maintain the electroneutrality of the solution, the aqueous solution of mixed inorganic salts should also contain an appropriate amount of counter anions (including but not limited to halide ions, such as fluoride, chloride, bromide, or iodide ions). In some embodiments, the aqueous solution of mixed inorganic salts contains about 10 mM of ammonia and / or ammonium ions. In some embodiments, the aqueous solution of mixed inorganic salts contains about 1 mM of ammonia and / or ammonium ions. In some embodiments, the aqueous solution of mixed inorganic salts is a mixed aqueous solution of sodium halide, potassium halide, and ammonium halide. In some embodiments, the aqueous solution of mixed inorganic salts is a mixed aqueous solution of sodium chloride, potassium chloride, and ammonium chloride. In some embodiments, the aqueous solution of mixed inorganic salts is prepared by dissolving 534.9 mg of ammonium chloride, 2922.2 mg of sodium chloride, and 3727.5 mg of potassium chloride in 1 L of pure water. In some embodiments, the aqueous solution of the mixed inorganic salts is prepared by dissolving 534.9 mg of ammonium chloride, 5844.3 mg of sodium chloride, and 7455.5 mg of potassium chloride in 1 L of pure water.

[0037] As used throughout this document, the term "fasted-state simulated colonic fluid (FaSSCOF)" refers to a solution that simulates the intestinal fluid in the colon during a pre-meal fasting state. FaSSCOF can be prepared using methods well-known to those skilled in the art. In some embodiments, FaSSCOF is prepared as follows: Dissolve 258.3 mg sodium cholate, 321.9 mg lecithin, 160.9 mg sodium oleate, 1.36 g sodium hydroxide, 3.7553 g TRIS hydrochloride, 3.4821 g maleic acid, and 2.4 g sodium hydroxide in 500 mL of water. Adjust the pH to 6.0 with NaOH or HCl, and then add water to a final volume of 1000 mL. In some implementations, a simulated fasting colonic solution containing approximately 10 mM of ammonia and / or ammonium ions is prepared as follows: Take 534.9 mg ammonium chloride, 258.3 mg sodium cholate, 321.9 mg lecithin, 160.9 mg sodium oleate, 1.36 g sodium hydroxide, 3.7553 g TRIS hydrochloride, 3.4821 g maleic acid, and 2.4 g sodium hydroxide, add 500 mL of water to dissolve them, adjust the pH to 6.0 with NaOH or HCl, and add water to a final volume of 1000 mL.

[0038] As used throughout this document, the term "fed-state simulated colonic fluid (FeSSCOF)" refers to a solution that simulates the intestinal fluid in the colon of a person in a state of fullness after a meal. FeSSCOF can be prepared by methods well known to those skilled in the art. In some embodiments, FeSSCOF is prepared as follows: Dissolve 64.584 mg sodium cholate, 193.1625 mg lecithin, 30.446 mg sodium oleate, 4.8 g sodium hydroxide, 5.4513 g TRIS hydrochloride, 8.821 g maleic acid, and 6.08 g sodium hydroxide in 500 mL of water. Adjust the pH to 7.8 with NaOH or HCl, and then add water to a final volume of 1000 mL. In some implementations, a simulated ingested colonic fluid containing approximately 10 mM of ammonia and / or ammonium ions is prepared as follows: Take 534.9 mg ammonium chloride, 64.584 mg sodium cholate, 193.1625 mg lecithin, 30.446 mg sodium oleate, 4.8 g sodium hydroxide, 5.4513 g TRIS hydrochloride, 8.821 g maleic acid, and 6.08 g sodium hydroxide, add 500 mL of water to dissolve them, adjust the pH to 7.8 with NaOH or HCl, and add water to a final volume of 1000 mL.

[0039] As used throughout this article, the term "standard atmosphere" refers to the air pressure at sea level under standard atmospheric conditions. One standard atmosphere (i.e., 1 atm) is 101.325 kPa.

[0040] As used throughout this article, the term "ammonia," also known as "ammonia gas" or "ammonia," refers to a substance with the formula NH3. Ammonia is a colorless gas at room temperature and pressure, has a strong, pungent odor (like urine), and is highly soluble in water to form ammonia water. Ammonia water is a weakly alkaline liquid; in ammonia water, ammonia molecules undergo slight hydrolysis to produce hydroxide ions and ammonium ions.

[0041] As used throughout this article, the term "ammonium ion" (also known as "ammonium, ammonium ion radical") is a monovalent, positively charged ion derived from ammonia (NH4+). + In acidic environments, ammonia molecules dissolved in water mainly exist in the form of ammonium ions.

[0042] As used throughout this article, the terms "ammonia and / or ammonium ions" refer to ammonia (NH3) in molecular form and ammonium ions (NH4) in ionic form. +Ammonia can exist in solution in both molecular and ionic forms, depending on the pH of the solution, and these two forms can interconvert to some extent. The higher the pH of the solution, the higher the proportion of ammonia existing in molecular form. Since the ammonia content measured when detecting a solution using IC (ion chromatography) is the total concentration of ammonia and ammonium ions, the "ammonia absorption capacity" of each substance measured in the embodiments of this disclosure actually refers to the sum of the absorption capacities of that substance for both ammonia and ammonium.

[0043] As used throughout this article, the term "blood ammonia" refers to ammonia that enters the bloodstream from various sources. Ammonia exists in the blood in two different forms: ammonia (NH3) and ammonium (NH4). + Both ammonia and ammonium exist simultaneously and, depending on the pH of the blood, can interconvert to some extent. Therefore, the term "blood ammonia" as used herein encompasses the sum of both ammonia and ammonium in the blood.

[0044] As used throughout this document, the term "appropriate level of ammonia and / or ammonium ions" refers to a level of ammonia and / or ammonium ions that will not cause unacceptable toxicity associated with excessive ammonia in a subject. Appropriate levels of ammonia and / or ammonium ions vary depending on the subject's sex, age, weight, general health condition, medical history, etc., but are generally ≥ about 5 μmol / L, ≥ about 10 μmol / L, ≥ about 15 μmol / L, ≥ about 20 μmol / L, ≥ about 25 μmol / L, or ≥ about 30 μmol / L and ≤ about 100 μmol / L, ≤ about 95 μmol / L, ≤ about 90 μmol / L, ≤ about 85 μmol / L, or ≤ about 80 μmol / L. For example, in some embodiments, appropriate levels of ammonia and / or ammonium ions are ≥ about 5 μmol / L and ≤ about 100 μmol / L, ≥ about 10 μmol / L and ≤ about 90 μmol / L, or ≥ about 20 μmol / L and ≤ about 80 μmol / L.

[0045] As used throughout this document, the term "disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject" refers to a disease or condition caused by an inappropriate elevation of ammonia and / or ammonium ion levels in the blood and / or digestive tract of a subject, or a disease or condition of a subject accompanied by an inappropriate elevation of ammonia and / or ammonium ion levels in the blood and / or digestive tract. In some embodiments, the disease or condition associated with elevated levels of ammonia and / or ammonium ion levels in the blood and / or digestive tract of a subject is hyperammonemia or a disease or condition associated with hyperammonemia. In some embodiments, the disease or condition associated with hyperammonemia is a urea cycle disorder. In some embodiments, the disease or condition associated with hyperammonemia is a liver disease. In some embodiments, the liver disease is selected from one or more of hepatitis, cirrhosis, hepatic encephalopathy, acute liver failure, chronic liver failure, and liver cancer. In some embodiments, the hepatitis is selected from one or more of viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, hepatitis caused by toxic substances, fulminant hepatitis, α1-antitrypsin deficiency, and non-alcoholic steatohepatitis. In some embodiments, the viral hepatitis is selected from one or more of hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, hepatitis F, and hepatitis G. In some embodiments, the disease or condition associated with hyperammonemia is selected from organic acidemia, such as propionic acidemia, isovaleric acidemia, methylmalonic acidemia, or 3-methylcrotonylglycinuria; fatty acid oxidation deficiency; carnitine deficiency; carnitine cycle deficiency; β-oxidation deficiency; lysineuric protein intolerance; pyrroline-5-carboxylic acid synthase deficiency; pyruvate carboxylase deficiency; ornithine aminotransferase deficiency; carbonic anhydrase deficiency; hyperinsulinemia-hyperammonia syndrome; mitochondrial disease; portal hypertension; chronic fatigue syndrome; central nervous system disorders, such as brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, hyperactivity, delusions, hallucinations, hyperactivity, coma, or cognitive impairment; growth retardation; and organ failure, such as respiratory failure, cardiovascular failure, or renal failure, or one or more of these.

[0046] As used throughout this document, the term "hyperammonemia" is a clinical syndrome characterized by an inappropriately elevated blood ammonia level and central nervous system dysfunction. The normal reference range for blood ammonia levels is 27–82 μmol / L. Blood ammonia levels in patients with hyperammonemia are typically 234.8–587 μmol / L. In cases of hepatic encephalopathy-induced coma due to hyperammonemia, blood ammonia levels can reach as high as 352.2–1526.2 μmol / L. In some embodiments, the hyperammonemia is caused by one or more of the following factors: glutamine synthetase deficiency; valproic acid therapy; asparaginase therapy; total parenteral nutrition; cystoscopy with a glycine-containing solution; lung or bone marrow transplantation; portosystemic shunt; ureteral dilatation; multiple myeloma; chemotherapy; infections such as urinary tract infections; neurogenic bladder; and intestinal bacterial overgrowth.

[0047] As used throughout this document, the term "urea cycle disorder (UCD)" refers to a group of congenital diseases in which a mutation occurs in the gene for at least one of the six major enzymes associated with the urea cycle (carbamoyl phosphate synthase (CPS), arginine succinate synthase (AS), arginine succinate lyase (AL), arginase (ARG), N-acetylglutamate synthase (NAGS), and ornithine transcarbamate (OTC)). This mutation prevents ammonia produced by amino acid catabolism from being excreted as urea through the urea cycle, resulting in elevated blood ammonia levels and a series of clinical manifestations, with brain dysfunction as the prominent feature. In some embodiments, the urea cycle disorder is selected from one or more of citrullinemia, argininosuccinateuria, arginase deficiency, N-acetylglutamate synthase deficiency, carbamoyl phosphate synthase deficiency, and ornithine transcarbamate deficiency.

[0048] As used throughout this article, the term "hepatic encephalopathy (HE)," also known as hepatic coma, refers to a syndrome of central nervous system dysfunction caused by severe liver disease and based on metabolic disorders. Its main clinical manifestations are altered consciousness and behavioral abnormalities; in severe cases, coma may occur. It is believed that an important underlying pathogenesis of hepatic encephalopathy is hyperammonemia, which is the result of excessive accumulation of ammonia in the blood.

[0049] As used throughout this document, the term "organic acidemia (OA)" refers to a group of diseases characterized by the accumulation of abnormal (often toxic) organic acid metabolites and increased urinary organic acid excretion (primarily due to a deficiency of specific enzymes in the amino acid breakdown pathway), leading to a series of pathophysiological changes and clinical symptoms. In some embodiments, the organic acidemia is propionic acidemia, isovaleric acidemia, methylmalonic acidemia, or 3-methylcrotonylglycinuria.

[0050] As used throughout this article, the term "urea" is a substance with the chemical formula (NH2)2CO. In the body, urea is synthesized in the liver as a waste product of protein digestion through a metabolic process known as the "urea cycle." It then enters the bloodstream and is primarily excreted through the kidneys in urine. A small amount of urea is also excreted through the feces via the intestines.

[0051] As used throughout this article, the term "blood urea nitrogen (BUN)" refers to the amount of nitrogen in urea present in a subject's blood, as measured by a medical test. The normal range for BUN is 2.1–7.1 mmol / L. BUN is one of the main indicators of kidney function insufficiency. When the glomerular filtration rate (GFR) decreases or blood volume is severely reduced, urea accumulates in the blood, and the BUN level increases accordingly.

[0052] As used throughout this document, the term "appropriate level of urea or blood urea nitrogen in a subject's blood" refers to a level of urea or blood urea nitrogen that will not cause unacceptable toxicity associated with excessive urea in the subject's blood. Appropriate levels of urea or blood urea nitrogen vary depending on the subject's sex, age, weight, general health condition, medical history, etc., but generally refer to blood urea nitrogen ≥ about 1.5 mmol / L and ≤ about 7.5 mmol / L. For example, in some embodiments, appropriate levels of urea or blood urea nitrogen in a subject are defined as blood urea nitrogen ≥ about 2 mmol / L and ≤ about 7 mmol / L, ≥ about 2.5 mmol / L and ≤ about 6.5 mmol / L, or ≥ about 3 mmol / L and ≤ about 6 mmol / L.

[0053] As used throughout this document, the term "disease or condition associated with elevated urea levels in a subject's blood" refers to a disease or condition caused by an inappropriate elevation in the subject's blood urea levels, or a disease or condition in the subject accompanied by an inappropriate elevation in blood urea levels. In some embodiments, the disease or condition associated with elevated urea levels in a subject's blood is azotemia. In other embodiments, the disease or condition associated with the elevated urea level in the subject's blood is selected from one or more of the following diseases or conditions: acute renal failure (e.g., acute renal failure caused by one or more of the following factors: acute tubular necrosis, acute nephritis, bacterial infection, and drug poisoning), chronic renal failure (e.g., chronic renal failure caused by one or more of the following factors: chronic glomerulonephritis, diabetes, hypertension, and polycystic kidney disease), uremia, heart failure, myocardial infarction, cardiorenal syndrome, gastrointestinal bleeding, dehydration, fluid loss, diabetes, hyperthyroidism, Cushing's syndrome, bacterial infection, sepsis, drug poisoning, heavy metal poisoning, burns, trauma, malignant tumors, cachexia, side effects of chemotherapy, anorexia, rhabdomyolysis syndrome, chronic liver disease, acute-on-chronic liver disease, and ascites.

[0054] As used throughout this document, the term "azotemia" is a condition characterized by abnormally elevated levels of nitrogenous compounds (such as urea and other nitrogen-rich compounds) in the blood. Azotemia largely reflects inadequate or dysfunctional filtration of blood by the kidneys in a subject. In some embodiments, azotemia is specifically hyperureaemia. In some embodiments, hyperureaemia is caused by excessive urea production in the subject's body. In some embodiments, hyperureaemia is caused by insufficient urea excretion in the subject. Depending on the etiology, azotemia can be classified into three main categories: prerenal azotemia, renal azotemia, or postrenal azotemia. Prerenal azotemia is characterized by reduced renal blood flow (insufficient perfusion), leading to the accumulation of urea in the blood. In some embodiments, prerenal azotemia is caused by one or more of the following factors: hemorrhage, shock, hypovolemia, congestive heart failure, adrenal insufficiency, and renal artery stenosis. Renal azotemia is an intrinsic disease of the kidney, usually resulting from damage to the renal parenchyma. Postrenal azotemia is characterized by obstruction of urine flow in the area below the kidney. In some embodiments, the postrenal azotemia is caused by one or more of the following factors: vesicoureteral reflux, ureteral obstruction, pregnancy, ureteral compression, benign prostatic hyperplasia, and urethral obstruction.

[0055] As used throughout this document, the terms “application” and “administration” are used interchangeably and refer to the process of introducing the medicament (or pharmaceutical composition) of this disclosure into the body of an individual by any route of introduction or delivery. Application may be performed using any method known to those skilled in the art for contacting cells, tissues, or organs with the medicament (or pharmaceutical composition). Routes of application may include, but are not limited to, oral or rectal administration. In some embodiments, the rectal administration method is administration via enema.

[0056] As used throughout this document, the term "prevention" means preventing the onset of a disease or condition in a subject at risk of developing the disease, or the recurrence of a previously resolved disease or condition, and the term "treatment" means controlling, reducing, or alleviating the pathological progression of a disease or condition and prolonging the survival of a subject with the disease or condition. Therefore, in the context of this disclosure, the terms "prevention and / or treatment" encompass the prevention of the onset or further increase in the severity of a disease or condition or one or more associated symptoms; the reduction and / or alleviation of the severity and / or duration of a disease or condition or one or more associated symptoms; the slowing or reversal of the progression of a disease or condition or one or more associated symptoms; the prevention, reduction, or reversal of any physiological damage caused by a disease or condition or one or more associated symptoms; and any pharmacological effects that are generally beneficial to a subject receiving treatment.

[0057] As used throughout this document, the terms “subject,” “object,” “individual,” and “patient” are used interchangeably and refer to a person or non-human mammal (e.g., non-human primates, canines, equines, felines, suidae, bovids, ungulates, lagomorphs, etc.) who requires diagnosis, improvement, prevention, and / or treatment of a disease or condition. In some embodiments, the subject is a human being, such as a newborn, infant, boy, girl, adolescent male, adolescent female, adult male, adult female, elderly male, or elderly female. In some embodiments, the subject is a non-human mammal. In some embodiments, the subject is a non-human primate (e.g., apes (such as gibbons), orangutans (such as gorillas, chimpanzees), macaques, cynomolgus monkeys, rhesus monkeys), companion animals (e.g., dogs and cats), farm animals (e.g., poultry, such as chickens, ducks, horses, cattle, goats, sheep, pigs), and laboratory animals (e.g., mice, rats, rabbits, guinea pigs).

[0058] As used throughout this article, the terms “disease,” “symptom,” “condition,” and “(medical) condition” are used interchangeably and refer to any deviation of an individual from a normal state. For example, these terms can refer to an individual’s physical discomfort or pain, or to any change in the state of certain organs or tissues that hinders or disrupts the normal functioning of those organs or tissues.

[0059] As used throughout this article, the term "absorption" refers to the process or action by which an adsorbent absorbs substances present in the environment (such as ammonia and / or ammonium ions) into the adsorbent and / or attaches them to the surface of the adsorbent.

[0060] Detailed description of the implementation plan

[0061] Unbound by any theory, it is believed that, at least in some embodiments (such as those shown in the examples), the compound of Formula I described herein is an active pharmaceutical ingredient capable of safely and effectively clearing ammonia and / or ammonium ions and urea present in the digestive tract of a subject by oral administration, thereby beneficially reducing the levels of ammonia and / or ammonium ions and urea in the subject's blood. In particular, when the liver or kidneys of a subject have a decreased ability to metabolize and / or excrete ammonia and / or ammonium ions and / or urea for some reason, oral administration of the compound of Formula I described herein will have a particularly beneficial effect on improving and alleviating inappropriate elevations or accumulations of ammonia and / or ammonium ions and urea in the subject's blood by clearing ammonia and / or ammonium ions and urea present in the subject's digestive tract.

[0062] The inventors have unexpectedly discovered that some of the compounds of Formula I described herein (i.e., those shown in the examples) possess the advantageous property of excellent absorption or scavenging of ammonia and / or ammonium ions in aqueous solutions. The inventors have also unexpectedly discovered that this absorption or scavenging effect of the compounds of Formula I on ammonia and / or ammonium ions is less affected by various components (including, but not limited to, other cations such as potassium or sodium ions and various organic components present in digestive fluids) that may be present in the contents of the subject's digestive tract (e.g., intestines). The inventors have also unexpectedly discovered that when the compounds of Formula I are orally administered to model animals, they can effectively reduce blood ammonia levels, cerebrospinal fluid ammonia levels, and blood urea nitrogen levels in the animals, with almost no effect on electrolyte levels such as magnesium, phosphorus, and sodium in the animal's blood. Therefore, the inventors foresaw that the compound of Formula I could be used as an active pharmaceutical ingredient in the preparation of pharmaceutical compositions or drugs, for example, for treating situations related to inappropriately elevated ammonia and / or ammonium ion levels and / or urea levels in the blood and / or digestive tract of a subject, or in methods for treating situations related to inappropriately elevated ammonia and / or ammonium ion levels and / or urea levels in the blood and / or digestive tract of a subject.

[0063] The implementation schemes of the various aspects described in this disclosure are based, at least in part, on the aforementioned unexpected findings.

[0064] Exemplary embodiments of this disclosure are provided below. It should be noted that the headings below are provided for layout purposes only and do not in any way limit the subject matter described herein. Furthermore, unless otherwise expressly stated or there is a clear mutual exclusion, the technical features of the various more specific embodiments described below with respect to the first aspect also apply to the other aspects.

[0065] Compounds of Formula I

[0066] In the first aspect, this disclosure provides a compound of formula I:

[0067] Mg3(PO4 3- ) a M b (HPO4 2- ) c (OH) d

[0068] I

[0069] Where M is selected from alkali metal ions, ammonium ions or any combination thereof; a≥1.5; b>0; c≥0; d≥0; where when a<2, c<0.4.

[0070] In some implementations, M is selected from Li + Na + K + NH4 + Or any combination thereof. In some embodiments, M is selected from Li + Na + Or any combination thereof. In some embodiments, M is selected from K. + Na + Or any combination thereof. In some embodiments, M is Na. + or K + In some implementations, M is Li + In some implementations, M is Na. + In some implementations, M is K. + In some implementations, M is NH4. + In some implementations, M is Li + Na + K + NH4 + A combination of two or more of them.

[0071] In some implementations, 1.7 ≤ a ≤ 6. In some implementations, 2 ≤ a ≤ 4. In some implementations, 2 ≤ a ≤ 3.5. In some implementations, a is 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6. In some implementations, a is 1.7, 2, 2.2, or 3.1.

[0072] In some implementations, 0.4 ≤ b ≤ 6. In some implementations, 0.5 ≤ b ≤ 4. In some implementations, 0.6 ≤ b ≤ 3.5. In some implementations, b is 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6. In some implementations, b is 0.4, 0.5, 0.8, 1.6, 2.4, 2.8, or 3.7.

[0073] In some implementations, 0 ≤ c ≤ 2. In some implementations, 0.1 ≤ c ≤ 1.5. In some implementations, 0.2 ≤ c ≤ 1.4. In some implementations, c is 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2. In some implementations, c is 0, 0.1, 0.2, 1.2, or 1.4.

[0074] In some implementations, 0 ≤ d ≤ 2. In some implementations, 0.2 ≤ d ≤ 1.8. In some implementations, 0.4 ≤ d ≤ 1.6. In some implementations, d is 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2. In some implementations, d is 0, 0.4, 1.4, or 1.6.

[0075] In some implementations, when a < 2, c ≤ 0.3, ≤ 0.2, ≤ 0.1, or 0. In some implementations, when a < 2, c is 0.

[0076] In some embodiments, 0.5 ≤ (a+c) / 3 ≤ 3.5. “(a+c) / 3” represents the molar ratio of the sum of phosphate and hydrogen phosphate ions to magnesium ions in the molecule of formula I. In some embodiments, 0.55 ≤ (a+c) / 3 ≤ 2. In some embodiments, 0.6 ≤ (a+c) / 3 ≤ 1.5. In some embodiments, 0.66 ≤ (a+c) / 3 ≤ 1.13. In some implementations, (a+c) / 3 is 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, or 3.5, or any value within any subrange of these values.

[0077] In some embodiments, the compound of Formula I is an amorphous form. In some embodiments, the compound of Formula I is in crystalline form.

[0078] In some embodiments, the compound of Formula I contains a total of ≤30 w / w% or ≤25 w / w% water. In some embodiments, the compound of Formula I contains a total of ≤20 w / w% water. The water may be water of crystallization or amorphous water. In some embodiments, the compound of Formula I contains a total of ≤17.5 w / w%, ≤15 w / w%, or ≤12.5 w / w% water. In some embodiments, the compound of Formula I contains a total of ≤30 w / w%, ≤29 w / w%, ≤28 w / w%, ≤27 w / w%, ≤26 w / w%, ≤25 w / w%, ≤24 w / w%, ≤23 w / w%, ≤22 w / w%, ≤21 w / w%, ≤20 w / w%, ≤19 w / w%, ≤18 w / w%, or ≤17 w / w% water. %, ≤16w / w%, ≤15w / w%, ≤14w / w%, ≤13w / w%, ≤12w / w%, ≤11w / w%, ≤10w / w%, ≤9w / w%, ≤ 8w / w%, ≤7w / w%, ≤6w / w%, ≤5w / w%, ≤4w / w%, ≤3w / w%, ≤2w / w%, ≤1w / w% or ≤0.5w / w% water.

[0079] In some embodiments, the compound of Formula I is in a non-gel solid form. In some embodiments, the compound of Formula I is in a sheet-like solid form. In some embodiments, the compound of Formula I is non-thixotropic. In some embodiments, the compound of Formula I is orally non-absorbable or substantially non-absorbable. The term "orally substantially non-absorbable" means that the amount of the compound of Formula I absorbed into the bloodstream through the gastrointestinal tract after oral administration is less than about 20 w / w of the administered dose, for example less than about 15 w / w%, 10 w / w%, 5 w / w%, 4 w / w%, 3 w / w%, 2 w / w%, 1 w / w%, 0.5 w / w%, 0.1 w / w%, 0.05 w / w%, 0.02 w / w%, or 0.01 w / w of the administered dose.

[0080] In some embodiments, when placed in an aqueous environment, the compound of Formula I absorbs ammonia and / or ammonium ions from the aqueous environment. In some embodiments, the compound of Formula I exhibits a clearance of ammonia and / or ammonium ions ≥ about 50% and / or an ammonia absorption capacity ≥ about 1 mmol / g, as measured in water containing about 10 mM of ammonia and / or ammonium ions, within about 24 hours. In some embodiments, the compound of Formula I exhibits a clearance of ammonia and / or ammonium ions ≥ about 70% and / or an ammonia absorption capacity ≥ about 1.5 mmol / g, as measured in water containing about 10 mM of ammonia and / or ammonium ions, within about 24 hours. In some embodiments, the compound of Formula I exhibits a clearance of ammonia and / or ammonium ions ≥ about 90% and / or an ammonia absorption capacity ≥ about 1.8 mmol / g, as measured in water containing about 10 mM of ammonia and / or ammonium ions, within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging capacity of ≥ about 55%, ≥ about 60%, ≥ about 65%, ≥ about 70%, ≥ about 75%, ≥ about 80%, ≥ about 85%, ≥ about 90%, or ≥ about 95% in water containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits an ammonia absorption capacity of ≥ about 1.1 mmol / g, ≥ about 1.2 mmol / g, ≥ about 1.3 mmol / g, ≥ about 1.4 mmol / g, ≥ about 1.5 mmol / g, ≥ about 1.6 mmol / g, ≥ about 1.7 mmol / g, ≥ about 1.8 mmol / g, ≥ about 1.85 mmol / g, or ≥ about 1.9 mmol / g in water containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥40% and / or an ammonia absorption capacity ≥0.8 mmol / g in an aqueous solution containing a mixed inorganic salt of about 10 mM ammonia and / or ammonium ions, as measured within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥45%, ≥50%, ≥55%, ≥60%, ≥65%, ≥70%, ≥75%, or ≥80% in an aqueous solution containing a mixed inorganic salt of about 10 mM ammonia and / or ammonium ions, as measured within about 24 hours. In some embodiments, the compound of Formula I exhibits an ammonia absorption capacity ≥ about 0.9 mmol / g, about 1 mmol / g, ≥ about 1.1 mmol / g, ≥ about 1.2 mmol / g, ≥ about 1.3 mmol / g, or ≥ about 1.4 mmol / g, as measured in an aqueous solution of a mixed inorganic salt containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the aqueous solution of the mixed inorganic salt is an aqueous solution containing an alkali metal halide in addition to ammonia and / or ammonium ions. In some embodiments, the aqueous solution of the mixed inorganic salt is a mixed aqueous solution of sodium halide, potassium halide, and ammonium halide.In some embodiments, the aqueous solution of the mixed inorganic salts is a mixed aqueous solution of sodium chloride, potassium chloride, and ammonium chloride. In some embodiments, the aqueous solution of the mixed inorganic salts is prepared as follows: take 534.9 mg of ammonium chloride, 2922.2 mg of sodium chloride, and 3727.5 mg of potassium chloride, and add water to a final volume of 1000 mL. In some embodiments, the aqueous solution of the mixed inorganic salts is prepared as follows: take 534.9 mg of ammonium chloride, 5844.3 mg of sodium chloride, and 7455.5 mg of potassium chloride, and add water to a final volume of 1000 mL. In some embodiments, the compound of Formula I exhibits a scavenging rate of ammonia and / or ammonium ions ≥ about 30% and / or an ammonia absorption capacity ≥ about 0.5 mmol / g in FaSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging capacity for ammonia and / or ammonium ions of ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, or ≥60% in FaSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits an ammonia absorption capacity of ≥0.6 mmol / g, ≥0.7 mmol / g, ≥0.8 mmol / g, ≥0.9 mmol / g, about 1 mmol / g, or ≥1.1 mmol / g in FaSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, FaSSCOF containing about 10 mM ammonia and / or ammonium ions is prepared as follows: Dissolve 534.9 mg ammonium chloride, 258.3 mg sodium cholate, 321.9 mg lecithin, 160.9 mg sodium oleate, 1.36 g sodium hydroxide, 3.7553 g TRIS hydrochloride, 3.4821 g maleic acid, and 2.4 g sodium hydroxide in 500 mL of water. Adjust the pH to 6.0 with NaOH or HCl, and then add water to a final volume of 1000 mL. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥30% and / or an ammonia absorption capacity ≥0.6 mmol / g for ammonia and / or ammonium ions in FeSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging capacity for ammonia and / or ammonium ions of ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, or ≥60% in FeSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours. In some embodiments, the compound of Formula I exhibits an ammonia absorption capacity of ≥0.7 mmol / g, ≥0.8 mmol / g, ≥0.9 mmol / g, about 1 mmol / g, ≥1.1 mmol / g, or ≥1.2 mmol / g in FeSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 hours.In some embodiments, FeSSCOF containing about 10 mM ammonia and / or ammonium ions is prepared as follows: Dissolve 534.9 mg ammonium chloride, 64.584 mg sodium cholate, 193.1625 mg lecithin, 30.446 mg sodium oleate, 4.8 g sodium hydroxide, 5.4513 g TRIS hydrochloride, 8.821 g maleic acid, and 6.08 g sodium hydroxide in 500 mL of water. Adjust the pH to 7.8 with NaOH or HCl, and bring the volume to 1000 mL. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥ about 60% and / or an ammonia absorption capacity ≥ about 1.3 mmol / g in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, as measured within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥70% and / or an ammonia absorption capacity of ≥1.5 mmol / g in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, as measured within about 24 hours. In some embodiments, the compound of Formula I exhibits a scavenging rate of ≥75%, ≥80%, ≥85%, or ≥90% in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, as measured within about 24 hours. In some embodiments, the compound of Formula I exhibits an ammonia absorption capacity of ≥1.55 mmol / g, ≥1.6 mmol / g, ≥1.65 mmol / g, ≥1.7 mmol / g, ≥1.75 mmol / g, or ≥1.8 mmol / g in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, as measured within about 24 hours. In some embodiments, the additive is selected from alkali metal halides, alkali metal carbonates, alkali metal bicarbonates, alkali metal sulfates, alkali metal bisulfates, alkali metal phosphates, alkali metal hydrogen phosphates, alkali metal dihydrogen phosphates, alkaline earth metal halides, alkaline earth metal carbonates, alkaline earth metal bicarbonates, alkaline earth metal sulfates, alkaline earth metal bisulfates, alkaline earth metal phosphates, alkaline earth metal hydrogen phosphates, and alkaline earth metal dihydrogen phosphates, provided that the additive is readily soluble in water or water-soluble. In some embodiments, the additive is selected from (a) chlorides or bromides of sodium, potassium, magnesium, or calcium; (b) bicarbonates of sodium, potassium, magnesium, or calcium; (c) sulfates of sodium, potassium, magnesium, or calcium; and (d) hydrogen phosphates of sodium, potassium, magnesium, or calcium, provided that the additive is readily soluble in water or water-soluble. In some embodiments, the additive is selected from NaCl, NaHCO3, Na2SO4, Na2HPO4, KCl, MgCl2, and CaCl2. In some embodiments, the additive is NaCl. In some embodiments, the additive is NaHCO3. In some embodiments, the additive is Na2SO4.In some embodiments, the additive is Na₂HPO₄. In some embodiments, the additive is KCl. In some embodiments, the additive is MgCl₂. In some embodiments, the additive is CaCl₂. In some embodiments, the additive is selected from two, three, or more combinations of NaCl, NaHCO₃, Na₂SO₄, Na₂HPO₄, KCl, MgCl₂, and CaCl₂. In some embodiments, the concentration of the additive in the aqueous solution is from about 10 mM to about 150 mM. In some embodiments, the concentration of the additive in the aqueous solution is about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 105 mM, about 110 mM, about 115 mM, about 120 mM, about 125 mM, about 130 mM, about 135 mM, about 140 mM, about 145 mM, or about 150 mM. In some embodiments, the concentration of the additive in the aqueous solution is about 10 mM. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM. In some embodiments, the concentration of the additive in the aqueous solution is about 10 mM, and the additive is MgCl2. In some embodiments, the concentration of the additive in the aqueous solution is about 10 mM, and the additive is CaCl2. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM, and the additive is NaCl. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM, and the additive is NaHCO3. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM, and the additive is Na2SO4. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM, and the additive is Na2HPO4. In some embodiments, the concentration of the additive in the aqueous solution is about 150 mM, and the additive is KCl. In some embodiments, the scavenging rate of the compound of Formula I for ammonia and / or ammonium ions is measured at about 37°C, about 1 standard atmosphere, under oscillation conditions, and with a mass-to-volume ratio of 5 mg of the compound of Formula I to 1 mL of liquid medium. In some embodiments, when placed in an aqueous environment, the compound of Formula I selectively absorbs ammonia and / or ammonium ions relative to other cations also present in the aqueous environment. In some embodiments, the other cations are potassium or sodium ions.In some implementations, when administered orally to a subject, the compound of Formula I reduces the level of urea in the subject's blood and / or digestive tract.

[0081] In some embodiments, the compound of formula I is prepared by a method comprising the following steps: mixing phosphoric acid and magnesium phosphate pentahydrate in water and stirring to obtain mixture A; adding MOH or an aqueous solution thereof to mixture A and stirring to obtain mixture B; allowing mixture B to stand and age for a period of time to obtain a crude product; washing the crude product with water to remove soluble substances to obtain the compound of formula I, wherein the MOH is an alkali metal hydroxide, ammonium hydroxide, or any combination thereof. In some embodiments, the molar ratio of magnesium phosphate pentahydrate, phosphoric acid, and MOH is 1:1.5-9:3-21. In some embodiments, the molar ratio of magnesium phosphate pentahydrate, phosphoric acid, and MOH is 1:1.5-9:3-18. In some implementations, the number of moles of phosphoric acid feedstock relative to the number of moles of magnesium phosphate pentahydrate feedstock is 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9, and the number of moles of MOH feedstock is 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, or 21. In some embodiments, the molar ratio of magnesium phosphate, phosphoric acid, and MOH is 1:3:9, 1:9:18, 1:2:5, 1:1.5:3, or 1:6:21. In some embodiments, the stirring lasts for at least 3 minutes. In some embodiments, the stirring lasts for at least 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 minutes. In some embodiments, the stirring lasts for 5-30 minutes. In some embodiments, the MOH is LiOH, NaOH, KOH, NH4OH, or any combination thereof. In some embodiments, the MOH is LiOH, NaOH, or any combination thereof. In some embodiments, the MOH is NaOH, KOH, or any combination thereof. In some embodiments, the MOH is LiOH. In some embodiments, the MOH is NaOH. In some embodiments, the MOH is KOH. In some embodiments, the MOH is NH4OH.In some embodiments, the MOH is a combination of two or more of LiOH, NaOH, KOH, and NH4OH. In some embodiments, the aging process lasts for at least 1 minute. In some embodiments, the aging process lasts for at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 1.5 hours, or at least 2 hours. In some embodiments, the crude product is washed with water as follows: the crude product is mixed thoroughly with water, centrifuged, the supernatant is removed, and optionally the washing steps are repeated once or more. In some embodiments, the volume / volume ratio of the crude product to water is from 1 mL crude product / 2 mL water to 1 mL crude product / 32 mL water. In some embodiments, the volume / volume ratio of the crude product to water is 1 mL crude product / 2 mL water. In some embodiments, the volume / volume ratio of the crude product to water is 1 mL crude product / 4 mL water. In some embodiments, the volume / volume ratio of the crude product to water is 1 mL crude product / 8 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL of the crude product / 16 mL of water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL of the crude product / 32 mL of water. In some embodiments, washing steps 2, 3, 4, 5, 6, 7, 8, 9, or 10 are repeated. In some embodiments, the method further includes drying the compound of formula I to obtain the compound of formula I in a dried state.

[0082] In some embodiments, the compound of formula I has the chemical formula: Mg3(PO4) 3- )2Na 1.6 (HPO4 2- )0(OH) 1.6 Mg3(PO4) 3- )2Na 2.8 (HPO4 2- ) 1.4 (OH)0, Mg3(PO4) 3- ) 3.1 Na 3.7 (HPO4 2- )0(OH) 0.4 Mg3(PO4) 3- )2Na 2.4 (HPO4 2- ) 1.2 (OH)0, Mg3(PO4) 3- ) 2.2 Na 0.8 (HPO4 2- ) 0.1 (OH)0, Mg3(PO4)3- )2Na 0.4 (HPO4 2- ) 0.2 (OH)0 or Mg3(PO4) 3- ) 1.7 Na 0.5 (HPO4 2- )0(OH) 1.4 In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- )2Na 1.6 (HPO4 2- )0(OH) 1.6 In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- )2Na 2.8 (HPO4 2- ) 1.4 (OH)0. In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- ) 3.1 Na 3.7 (HPO4 2- )0(OH) 0.4 In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- )2Na 2.4 (HPO4 2- ) 1.2 (OH)0. In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- ) 2.2 Na 0.8 (HPO4 2- ) 0.1 (OH)0. In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- )2Na 0.4 (HPO4 2- ) 0.2 (OH)0. In some embodiments, the compound of formula I has the chemical formula Mg3(PO4). 3- ) 1.7 Na 0.5 (HPO4 2- )0(OH) 1.4 .

[0083] Methods for preparing compounds of formula I

[0084] In a second aspect, this disclosure provides a method for preparing the compound of formula I, comprising the following steps: mixing phosphoric acid and magnesium phosphate pentahydrate in water and stirring to obtain a mixture A; adding MOH or an aqueous solution thereof to mixture A and stirring to obtain a mixture B; allowing mixture B to stand and age for a period of time to obtain a crude product; washing the crude product with water to remove soluble substances to obtain the compound of formula I, wherein the MOH is an alkali metal hydroxide, ammonium hydroxide, or any combination thereof.

[0085] In some embodiments, the molar ratio of magnesium phosphate pentahydrate, phosphoric acid, and MOH is 1:1.5-9:3-21. In some embodiments, the molar ratio of magnesium phosphate pentahydrate, phosphoric acid, and MOH is 1:1.5-9:3-18. In some implementations, the number of moles of phosphoric acid feedstock relative to the number of moles of magnesium phosphate pentahydrate feedstock is 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9, and the number of moles of MOH feedstock is 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, or 21. In some embodiments, the molar ratio of magnesium phosphate, phosphoric acid, and MOH is 1:3:9, 1:9:18, 1:2:5, 1:1.5:3, or 1:6:21. In some embodiments, the stirring lasts for at least 3 minutes. In some embodiments, the stirring lasts for at least 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 minutes. In some embodiments, the stirring lasts for 5-30 minutes. In some embodiments, the MOH is LiOH, NaOH, KOH, NH4OH, or any combination thereof. In some embodiments, the MOH is LiOH, NaOH, or any combination thereof. In some embodiments, the MOH is NaOH, KOH, or any combination thereof. In some embodiments, the MOH is LiOH. In some embodiments, the MOH is NaOH. In some embodiments, the MOH is KOH. In some embodiments, the MOH is NH4OH. In some embodiments, the MOH is a combination of two or more of LiOH, NaOH, KOH, and NH4OH. In some embodiments, the standing aging lasts for at least 1 minute. In some embodiments, the standing aging lasts for at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 1.5 hours, or at least 2 hours. In some embodiments, the crude product is washed with water as follows: the crude product is mixed thoroughly with water, centrifuged, the supernatant is removed, and optionally the above washing steps are repeated once or more.In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 2 mL water to 1 mL crude product / 32 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 2 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 4 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 8 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 16 mL water. In some embodiments, the volume / volume ratio of the crude product mixed with water is 1 mL crude product / 32 mL water. In some embodiments, washing steps 2, 3, 4, 5, 6, 7, 8, 9, or 10 are repeated. In some embodiments, the method further includes drying the compound of formula I to obtain the compound of formula I in a dried state.

[0086] Pharmaceutical compositions comprising compounds of formula I

[0087] In a third aspect, this disclosure provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients.

[0088] In some embodiments, the pharmaceutically acceptable excipient is selected from solvents, dispersion media, coating agents, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents, etc.), isotensants, absorption delay agents, salts, stabilizers, fillers, binders, disintegrants, lubricants, flow aids, sweeteners, flavoring agents, dyes, etc., and one or more combinations thereof. In some embodiments, the pharmaceutically acceptable excipient is selected from: solvents, such as water, ethanol, glycerol, propylene glycol, DMSO, polyethylene glycol, fatty oils such as sesame oil, corn oil, cottonseed oil, or peanut oil, liquid paraffin, ethyl oleate, or isopropyl myristate; surfactants, such as sulfates, sulfonates, quaternary ammonium compounds, lecithin, Span derivatives, Tween derivatives, polyethylene glycol 40 stearate, phenazine O, or poloxamer; emulsifiers, such as gelatin, gum arabic, astragalus gum, bentonite, or surfactants such as polyoxyethylene sorbitan monooleate; suspending agents, such as sodium carboxymethyl cellulose, pectin, astragalus gum, magnesium aluminum silicate, or gum arabic; fillers, such as lactose, sucrose, trehalose, lysine, leucine, kaolin, calcium hydrogen phosphate, mannitol, microcrystalline cellulose, or pregelatinized starch; binders, such as cellulose, PVP, or dextrin; disintegrants, such as... Cross-linked sodium carboxymethyl cellulose, sodium glycolate starch, alginate, corn starch, potato starch, bentonite, methyl cellulose, agar, or hydroxypropyl starch; lubricants, such as talc, polyethylene glycol, calcium stearate, magnesium stearate, zinc stearate, or stearic acid; flow aids, such as colloidal silica; colorants, such as any approved, certified water-soluble or water-insoluble FD and C dyes (e.g., dyes suspended on alumina hydrate); wetting agents, such as propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, or polyoxyethylene lauryl ether; enteric coating agents, such as fatty acids, fats, waxes, shellac, ammoniated shellac, or cellulose acetate; film coating agents, such as hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000, or cellulose acetate; and sustained-release agents, such as Eudragit. Polymers such as series and cellulose esters; sweeteners, such as fructose, glucose, sucrose, artificial sweeteners such as sucralose, aspartame or saccharin, agave syrup, maple syrup or corn syrup; flavoring agents, such as natural flavorings extracted from fruits, mint and other plants or methyl salicylate; buffers, such as citrates, phosphates and other organic acids and / or their salts; antioxidants, such as ascorbic acid, methionine, citric acid, D,L-α-tocopherol, BHA, BHT, monothioglycerol, ascorbyl palmitate, ascorbic acid or propyl gallate; preservatives, such as benzoic acid, sodium benzoate, parabens such as methylparaben or propylparaben, sorbic acid or benzalkonium bromide; pH adjusters, such as citric acid, sodium citrate, hydrochloric acid, NaOH or other weak acids or weak bases; chelating agents or other materials capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA) or its salts.

[0089] In this respect, the present disclosure also provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4).

[0090] In this respect, the present disclosure also provides a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with elevated urea levels in the blood of a subject; or (5) two or more of (1) to (4) above.

[0091] In some embodiments, the pharmaceutical composition is used to prevent and / or treat a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the pharmaceutical composition is used to reduce the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the pharmaceutical composition is used to absorb ammonia and / or ammonium ions in the digestive tract of a subject. In some embodiments, the pharmaceutical composition is used to maintain appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the pharmaceutical composition is used for two, three, or four of the following: preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, absorbing ammonia and / or ammonium ions in the digestive tract of a subject, and maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject.

[0092] In some embodiments, the pharmaceutical composition is used to reduce the level of urea or blood urea nitrogen (BUN) in a subject's blood. In some embodiments, the pharmaceutical composition is used to reduce the level of urea in the gastrointestinal contents of a subject. In some embodiments, the pharmaceutical composition is used to maintain an appropriate level of urea or blood urea nitrogen in the subject's blood. In some embodiments, the pharmaceutical composition is used to prevent and / or treat a disease or condition associated with elevated urea levels in a subject's blood. In some embodiments, the pharmaceutical composition is used to reduce the level of urea or blood urea nitrogen (BUN) in a subject's blood, reduce the level of urea in the gastrointestinal contents of a subject, maintain an appropriate level of urea or blood urea nitrogen in the subject's blood, and prevent and / or treat two, three, or four of the following:

[0093] In some embodiments, the active ingredient of the pharmaceutical composition consists of a compound of formula I.

[0094] In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human or a non-human mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a human selected from newborns, infants, boys, girls, adolescent males, adolescent females, adult males, adult females, elderly males, or elderly females. In some embodiments, the mammal is a non-human mammal. In some embodiments, the non-human mammal is a non-human primate, canine, equine, feline, suidae, bovid, ungulate, or lagomorph. In some embodiments, the non-human primate is an ape (e.g., a gibbon), orangutan (e.g., a gorilla, chimpanzee), macaque, cynomolgus monkey, or rhesus monkey.

[0095] In some embodiments, the digestive tract is the stomach. In some embodiments, the digestive tract is the intestine. For example, in some embodiments, the digestive tract is the small intestine. In some embodiments, the digestive tract is the duodenum. In some embodiments, the digestive tract is the jejunum. In some embodiments, the digestive tract is the ileum. In some embodiments, the digestive tract is the large intestine. In some embodiments, the digestive tract is the cecum. In some embodiments, the digestive tract is the colon (e.g., one or more of the ascending colon, transverse colon, descending colon, and sigmoid colon). In some embodiments, the digestive tract is the rectum. In some embodiments, the digestive tract is the small intestine and / or large intestine. In some embodiments, the digestive tract is one or more of the duodenum, jejunum, and ileum. In some embodiments, the digestive tract is one or more of the cecum, colon, and rectum. In some embodiments, the digestive tract is one or more of the duodenum, jejunum, ileum, cecum, colon, and rectum.

[0096] In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 40 μmol / L, about 45 μmol / L, about 50 μmol / L, about 55 μmol / L, about 60 μmol / L, about 65 μmol / L, about 70 μmol / L, about 75 μmol / L, about 80 μmol / L, about 85 μmol / L, about 90 μmol / L, about 95 μmol / L, about 100 μmol / L, about 150 μmol / L, or about 200 μmol / L before the administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 40 μmol / L before the administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 45 μmol / L before the administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 50 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 55 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 60 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 65 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 70 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 75 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 80 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 85 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 90 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 95 μmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the subject's blood is higher than about 100 μmol / L before administration of the pharmaceutical composition to the subject.In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 150 μmol / L prior to administration of the pharmaceutical composition to the subject. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 200 μmol / L prior to administration of the pharmaceutical composition to the subject.

[0097] In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is about 200 μmol / L to about 1600 μmol / L, about 300 μmol / L to about 1500 μmol / L, about 400 μmol / L to about 1400 μmol / L, about 500 μmol / L to about 1300 μmol / L, or about 600 μmol / L to about 1200 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is about 200 μmol / L to about 1600 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is about 300 μmol / L to about 1500 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is from about 400 μmol / L to about 1400 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is from about 500 μmol / L to about 1300 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is from about 600 μmol / L to about 1200 μmol / L. In some embodiments, the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is about or at least about 200 μmol / L, about or at least about 300 μmol / L, about or at least about 400 μmol / L, about or at least about 500 μmol / L, about or at least about 600 μmol / L, about or at least about 700 μmol / L, about or at least about 800 μmol / L, about or at least about 900 μmol / L, about or at least about 1000 μmol / L, about or at least about 1100 μmol / L, about or at least about 1200 μmol / L, about or at least about 1300 μmol / L, about or at least about 1400 μmol / L, about or at least about 1500 μmol / L, or about 1600 μmol / L.

[0098] In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 5% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 10% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 15% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 20% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 25% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 30% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 35% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 40% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 45% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 50% for at least a certain period of time compared to before administration of the pharmaceutical composition.In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 60% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 70% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 80% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 90% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours. In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0099] In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1600 μmol / L, ≤ about 1500 μmol / L, ≤ about 1400 μmol / L, ≤ about 1300 μmol / L, ≤ about 1200 μmol / L, ≤ about 1100 μmol / L, ≤ about 1000 μmol / L, ≤ about 900 μmol / L, ≤ about 800 μmol / L, ≤ about 700 μmol / L, ≤ about 600 μmol / L, ≤ about 50 μmol / L for at least a certain period of time. 0 μmol / L, ≤ about 400 μmol / L, ≤ about 300 μmol / L, ≤ about 200 μmol / L, ≤ about 100 μmol / L, ≤ about 95 μmol / L, ≤ about 90 μmol / L, ≤ about 85 μmol / L, ≤ about 80 μmol / L, ≤ about 75 μmol / L, ≤ about 70 μmol / L, ≤ about 65 μmol / L, ≤ about 60 μmol / L, ≤ about 55 μmol / L, ≤ about 50 μmol / L, ≤ about 45 μmol / L, or ≤ about 40 μmol / L and ≥ about 5 μmol / L. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1600 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1500 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1400 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1300 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1200 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1100 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1000 μmol / L and ≥ about 5 μmol / L for at least a certain period of time.In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 900 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 800 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 700 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 600 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 500 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 400 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 300 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 200 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 100 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 95 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 90 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 85 μmol / L and ≥ about 5 μmol / L for at least a certain period of time.In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 80 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 75 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 70 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 65 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 60 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 55 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 50 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 45 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 40 μmol / L and ≥ about 5 μmol / L for at least a certain period of time. In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours.In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0100] In some implementations, the disease or condition associated with elevated levels of ammonia and / or ammonium ions in the subject's blood and / or digestive tract is hyperammonemia or a disease or condition associated with hyperammonemia.

[0101] In some embodiments, the disease or condition associated with elevated levels of ammonia and / or ammonium ions in the subject's blood and / or digestive tract is hyperammonemia. In some embodiments, the hyperammonemia is caused by one or more of the following factors: glutamine synthetase deficiency; valproic acid therapy; asparaginase therapy; total parenteral nutrition; cystoscopy with a glycine-containing solution; lung or bone marrow transplantation; portosystemic shunt; ureteral dilatation; multiple myeloma; chemotherapy; infection, such as urinary tract infection; neurogenic bladder; and intestinal bacterial overgrowth. In some embodiments, the hyperammonemia is caused by glutamine synthetase deficiency. In some embodiments, the hyperammonemia is caused by valproic acid therapy. In some embodiments, the hyperammonemia is caused by asparaginase therapy. In some embodiments, the hyperammonemia is caused by total parenteral nutrition. In some embodiments, the hyperammonemia is caused by cystoscopy with a glycine-containing solution. In some embodiments, the hyperammonemia is caused by lung or bone marrow transplantation. In some embodiments, the hyperammonemia is caused by portosystemic shunt. In some embodiments, the hyperammonemia is caused by ureteral dilatation. In some embodiments, the hyperammonemia is caused by multiple myeloma. In some embodiments, the hyperammonemia is caused by chemotherapy. In some embodiments, the hyperammonemia is caused by infection. In some embodiments, the hyperammonemia is caused by urinary tract infection. In some embodiments, the hyperammonemia is caused by neurogenic bladder. In some embodiments, the hyperammonemia is caused by intestinal bacterial overgrowth. In some implementations, the hyperammonemia is caused by two or more of the following: glutamine synthase deficiency; valproic acid therapy; asparaginase therapy; total parenteral nutrition; cystoscopy with a glycine-containing solution; lung or bone marrow transplantation; portosystemic shunt; ureteral dilatation; multiple myeloma; chemotherapy; infection such as urinary tract infection; neurogenic bladder; and intestinal bacterial overgrowth (e.g., three, four, five, six, seven, or eight).

[0102] In some implementations, the disease or condition associated with elevated levels of ammonia and / or ammonium ions in the subject's blood and / or digestive tract is a disease or condition associated with hyperammonemia.

[0103] In some embodiments, the disease or condition associated with hyperammonemia is a urea cycle disorder. In some embodiments, the urea cycle disorder is selected from one or more of citrullinemia, argininosuccinateuria, arginase deficiency, N-acetylglutamate synthase deficiency, carbamoyl phosphate synthase deficiency, and ornithine transcarbamate deficiency. In some embodiments, the disease or condition associated with hyperammonemia is citrullinemia. In some embodiments, the disease or condition associated with hyperammonemia is argininosuccinateuria. In some embodiments, the disease or condition associated with hyperammonemia is arginase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is N-acetylglutamate synthase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is carbamoyl phosphate synthase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is ornithine transcarbamate deficiency. In some implementations, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three, four, five or six) of citrullinemia, arginine succinateuria, arginase deficiency, N-acetylglutamate synthase deficiency, carbamoyl phosphate synthase deficiency and ornithine transcarbamoylase deficiency.

[0104] In some embodiments, the disease or condition associated with hyperammonemia is a liver disease. In some embodiments, the liver disease is selected from one or more of hepatitis, cirrhosis, hepatic encephalopathy, acute liver failure, chronic liver failure, and liver cancer. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis. In some embodiments, the hepatitis is selected from one or more of viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, hepatitis caused by toxic substances, fulminant hepatitis, α1-antitrypsin deficiency, and non-alcoholic steatohepatitis. In some embodiments, the disease or condition associated with hyperammonemia is viral hepatitis. In some embodiments, the viral hepatitis is selected from one or more of hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, hepatitis F, and hepatitis G. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis A. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis B. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis C. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis D. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis E. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis F. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis G. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three, four, five, six, or seven) of hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, hepatitis F, and hepatitis G. In some embodiments, the disease or condition associated with hyperammonemia is alcoholic hepatitis. In some embodiments, the disease or condition associated with hyperammonemia is drug-induced hepatitis. In some embodiments, the disease or condition associated with hyperammonemia is hepatitis caused by a toxic substance. In some embodiments, the disease or condition associated with hyperammonemia is fulminant hepatitis. In some embodiments, the disease or condition associated with hyperammonemia is alpha-1 antitrypsin deficiency. In some embodiments, the disease or condition associated with hyperammonemia is non-alcoholic steatohepatitis. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three, four, five, six, or seven) of viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, hepatitis caused by toxic substances, fulminant hepatitis, alpha-1 antitrypsin deficiency, and non-alcoholic steatohepatitis. In some embodiments, the disease or condition associated with hyperammonemia is cirrhosis. In some embodiments, the disease or condition associated with hyperammonemia is hepatic encephalopathy. In some embodiments, the disease or condition associated with hyperammonemia is acute liver failure. In some embodiments, the disease or condition associated with hyperammonemia is chronic liver failure.In some embodiments, the disease or condition associated with hyperammonemia is liver cancer. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three, four, five or six) of hepatitis, cirrhosis, hepatic encephalopathy, acute liver failure, chronic liver failure and liver cancer.

[0105] In some embodiments, the disease or condition associated with hyperammonemia is selected from organic acidemia, such as propionic acidemia, isovaleric acidemia, methylmalonic acidemia, or 3-methylcrotonylglycinuria; fatty acid oxidation deficiency; carnitine deficiency; carnitine cycle deficiency; β-oxidation deficiency; lysineuric protein intolerance; pyrroline-5-carboxylic acid synthase deficiency; pyruvate carboxylase deficiency; ornithine aminotransferase deficiency; carbonic anhydrase deficiency; hyperinsulinemia-hyperammonia syndrome; mitochondrial disease; portal hypertension; chronic fatigue syndrome; central nervous system disorders, such as brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, agitation, delusions, hallucinations, hyperactivity, coma, or cognitive impairment; growth retardation; and organ failure, such as respiratory failure, cardiovascular failure, or renal failure. In some embodiments, the disease or condition associated with hyperammonemia is organic acidemia. In some embodiments, the organic acidemia is selected from one or more of propionic acidemia, isovaleric acidemia, methylmalonic acidemia, and 3-methylcrotonylglycinuria. In some embodiments, the disease or condition associated with hyperammonemia is propionic acidemia. In some embodiments, the disease or condition associated with hyperammonemia is isovaleric acidemia. In some embodiments, the disease or condition associated with hyperammonemia is methylmalonic acidemia. In some embodiments, the disease or condition associated with hyperammonemia is 3-methylcrotonylglycinuria. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three or four) of propionic acidemia, isovaleric acidemia, methylmalonic acidemia, and 3-methylcrotonylglycinuria. In some embodiments, the disease or condition associated with hyperammonemia is a fatty acid oxidation defect. In some embodiments, the disease or condition associated with hyperammonemia is carnitine deficiency. In some embodiments, the disease or condition associated with hyperammonemia is a carnitine cycle defect. In some embodiments, the disease or condition associated with hyperammonemia is β-oxidation deficiency. In some embodiments, the disease or condition associated with hyperammonemia is lysineuric protein intolerance. In some embodiments, the disease or condition associated with hyperammonemia is pyrroline-5-carboxylic acid synthase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is pyruvate carboxylase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is ornithine aminotransferase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is carbonic anhydrase deficiency. In some embodiments, the disease or condition associated with hyperammonemia is hyperinsulinemia-hyperammonemia syndrome. In some embodiments, the disease or condition associated with hyperammonemia is mitochondrial disease. In some embodiments, the disease or condition associated with hyperammonemia is portal hypertension.In some embodiments, the disease or condition associated with hyperammonemia is chronic fatigue syndrome. In some embodiments, the disease or condition associated with hyperammonemia is a central nervous system disorder. In some embodiments, the central nervous system disorder is selected from one or more of the following: brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, agitation, delusions, hallucinations, hyperactivity, coma, and cognitive impairment. In some embodiments, the disease or condition associated with hyperammonemia is brain dysfunction. In some embodiments, the disease or condition associated with hyperammonemia is cerebral edema. In some embodiments, the disease or condition associated with hyperammonemia is slurred speech. In some embodiments, the disease or condition associated with hyperammonemia is tremor. In some embodiments, the disease or condition associated with hyperammonemia is ataxia. In some embodiments, the disease or condition associated with hyperammonemia is seizures. In some embodiments, the disease or condition associated with hyperammonemia is nausea. In some embodiments, the disease or condition associated with hyperammonemia is vomiting. In some embodiments, the disease or condition associated with hyperammonemia is hyperactivity. In some embodiments, the disease or condition associated with hyperammonemia is delusions. In some embodiments, the disease or condition associated with hyperammonemia is hallucinations. In some embodiments, the disease or condition associated with hyperammonemia is hyperactivity. In some embodiments, the disease or condition associated with hyperammonemia is coma. In some embodiments, the disease or condition associated with hyperammonemia is cognitive impairment. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three, four, five, six, seven, or eight) of brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, hyperactivity, delusions, hallucinations, hyperactivity, coma, and cognitive impairment. In some embodiments, the disease or condition associated with hyperammonemia is growth retardation. In some embodiments, the disease or condition associated with hyperammonemia is organ failure. In some embodiments, the organ failure is selected from one or more of respiratory failure, cardiovascular failure, and renal failure. In some embodiments, the disease or condition associated with hyperammonemia is respiratory failure. In some embodiments, the disease or condition associated with hyperammonemia is cardiovascular failure. In some embodiments, the disease or condition associated with hyperammonemia is renal failure. In some embodiments, the disease or condition associated with hyperammonemia is selected from two or more (e.g., three) of respiratory failure, cardiovascular failure, and renal failure.

[0106] In some embodiments, the subject's blood urea nitrogen level is higher than about 6 mmol / L, about 6.5 mmol / L, about 7 mmol / L, about 7.5 mmol / L, about 8 mmol / L, or about 8.5 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 6 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 6.5 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 7 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 7.5 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 8 mmol / L before administration of the pharmaceutical composition to the subject. In some embodiments, the subject's blood urea nitrogen level is higher than about 8.5 mmol / L before administration of the pharmaceutical composition to the subject.

[0107] In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 5% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 10% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 15% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 20% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 25% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 30% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 35% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 40% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 45% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 50% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 55% for at least a certain period of time compared to before administration of the pharmaceutical composition.In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 60% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 65% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 70% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 75% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 80% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 85% compared to before administration of the pharmaceutical composition for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 90% for at least a certain time period compared to before administration of the pharmaceutical composition. In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours. In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0108] In some embodiments, the pharmaceutical composition is used to reduce the urea level in the intestinal contents of the subject. In some embodiments, the intestine is the small intestine. In some embodiments, the intestine is the duodenum. In some embodiments, the intestine is the jejunum. In some embodiments, the intestine is the ileum. In some embodiments, the intestine is the large intestine. In some embodiments, the intestine is the cecum. In some embodiments, the intestine is the colon (e.g., one or more of the ascending colon, transverse colon, descending colon, and sigmoid colon). In some embodiments, the intestine is the rectum. In some embodiments, the intestine is the small intestine and / or large intestine. In some embodiments, the intestine is one or more of the duodenum, jejunum, and ileum. In some embodiments, the intestine is one or more of the cecum, colon, and rectum. In some embodiments, the intestine is one or more of the duodenum, jejunum, ileum, cecum, colon, and rectum.

[0109] In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 5% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 10% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 15% compared to before administration of the pharmaceutical composition, for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 20% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 25% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 30% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 35% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 40% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 45% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of urea in the subject's intestinal contents is reduced by at least about 50% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of urea in the subject's intestinal contents is reduced by at least about 55% for at least a certain period of time compared to before administration of the pharmaceutical composition.In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 60% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 65% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 70% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 75% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 80% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is reduced by at least about 85% for at least a certain period of time compared to before administration of the pharmaceutical composition. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of urea in the subject's intestinal contents decreases by at least about 90% for at least a certain time period compared to before administration of the pharmaceutical composition. In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours.In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0110] In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is ≤ about 100 mg / dL, ≤ about 90 mg / dL, ≤ about 80 mg / dL, ≤ about 70 mg / dL, ≤ about 60 mg / dL, ≤ about 50 mg / dL, ≤ about 40 mg / dL, ≤ about 30 mg / dL, or ≤ about 20 mg / dL for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is ≤ about 100 mg / dL for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is ≤ about 90 mg / dL for at least a certain period of time. In some embodiments, after administration of the pharmaceutical composition to the subject, the urea level in the subject's intestinal contents is ≤ about 80 mg / dL for at least a certain period of time. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 70 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 60 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 50 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 40 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 30 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, the urea level in the intestinal contents of the subject is ≤ about 20 mg / dL for at least a certain period of time after administration of the pharmaceutical composition to the subject. In some embodiments, after administration of the pharmaceutical composition to the subject, the level of urea in the subject's intestinal contents is at least for a certain period of time about 100 mg / dL, about 95 mg / dL, about 90 mg / dL, about 85 mg / dL, about 80 mg / dL, about 75 mg / dL, about 70 mg / dL, about 65 mg / dL, about 60 mg / dL, about 55 mg / dL, about 50 mg / dL, about 45 mg / dL, about 40 mg / dL, about 35 mg / dL, about 30 mg / dL, about 25 mg / dL, about 20 mg / dL, about 15 mg / dL, about 10 mg / dL, or about 5 mg / dL.In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours. In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0111] In some embodiments, after administration of the pharmaceutical composition to the subject, the pharmaceutical composition maintains a suitable level of urea or blood urea nitrogen in the subject's blood for at least a certain period of time. In some embodiments, the suitable subject's blood urea nitrogen level is ≥ about 1.5 mmol / L and ≤ about 7.5 mmol / L, ≥ about 2 mmol / L and ≤ about 7 mmol / L, ≥ about 2.5 mmol / L and ≤ about 6.5 mmol / L, or ≥ about 3 mmol / L and ≤ about 6 mmol / L. In some embodiments, the suitable subject's blood urea nitrogen level is ≥ about 1.5 mmol / L and ≤ about 7.5 mmol / L. In some embodiments, the suitable subject's blood urea nitrogen level is ≥ about 2 mmol / L and ≤ about 7 mmol / L. In some embodiments, the suitable subject's blood urea nitrogen level is ≥ about 2.5 mmol / L and ≤ about 6.5 mmol / L. In some embodiments, the suitable subject's blood urea nitrogen level is ≥ about 3 mmol / L and ≤ about 6 mmol / L. In some embodiments, the appropriate subject's blood urea nitrogen level is about 1.5 mmol / L, about 2 mmol / L, about 2.5 mmol / L, about 3 mmol / L, about 3.5 mmol / L, about 4 mmol / L, about 4.5 mmol / L, about 5 mmol / L, about 5.5 mmol / L, about 6 mmol / L, about 6.5 mmol / L, about 7 mmol / L, or about 7.5 mmol / L. In some embodiments, the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. In some embodiments, the time period is at least 0.5 hours. In some embodiments, the time period is at least 1 hour. In some embodiments, the time period is at least 2 hours. In some embodiments, the time period is at least 4 hours. In some embodiments, the time period is at least 6 hours. In some embodiments, the time period is at least 8 hours. In some embodiments, the time period is at least 12 hours. In some embodiments, the time period is at least 16 hours. In some embodiments, the time period is at least 20 hours. In some embodiments, the time period is at least 24 hours.In some implementations, the time period is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 hours.

[0112] In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is azotemia. In some embodiments, the azotemia is hyperureaemia. In some embodiments, the hyperureaemia is caused by excessive urea production or insufficient urea excretion in the subject. In some embodiments, the hyperureaemia is caused by excessive urea production in the subject. In some embodiments, the hyperureaemia is caused by insufficient urea excretion in the subject. In some embodiments, the azotemia is prerenal azotemia, renal azotemia, or postrenal azotemia. In some embodiments, the azotemia is prerenal azotemia. In some embodiments, the prerenal azotemia is caused by one or more of the following factors: hemorrhage, shock, hypovolemia, congestive heart failure, adrenal insufficiency, and renal artery stenosis. In some embodiments, the azotemia is renal azotemia. In some embodiments, the renal azotemia is caused by renal parenchymal damage. In some embodiments, the azotemia is postrenal azotemia. In some embodiments, the postrenal azotemia is caused by one or more of the following factors: vesicoureteral reflux, ureteral obstruction, pregnancy, ureteral compression, benign prostatic hyperplasia, and urethral obstruction. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is selected from one or more of the following: acute renal failure (e.g., acute renal failure caused by one or more of the following factors: acute tubular necrosis, acute nephritis, bacterial infection, and drug poisoning), chronic renal failure (e.g., chronic renal failure caused by one or more of the following factors: chronic glomerulonephritis, diabetes, hypertension, and polycystic kidney disease), uremia, heart failure, myocardial infarction, cardiorenal syndrome, gastrointestinal bleeding, dehydration, fluid loss, diabetes, hyperthyroidism, Cushing's syndrome, bacterial infection, sepsis, drug poisoning, heavy metal poisoning, burns, trauma, malignancy, cachexia, side effects of chemotherapy, anorexia, rhabdomyolysis, chronic liver disease, acute-on-chronic liver disease, and ascites. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is acute renal failure. In some embodiments, the acute renal failure is acute renal failure caused by one or more of the following factors: acute tubular necrosis, acute nephritis, bacterial infection, and drug poisoning. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is chronic renal failure. In some embodiments, the chronic renal failure is chronic renal failure caused by one or more of the following factors: chronic glomerulonephritis, diabetes, hypertension, and polycystic kidney disease. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is uremia.In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is heart failure. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is myocardial infarction. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is cardiorenal syndrome. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is gastrointestinal bleeding. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is dehydration. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is fluid loss. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is diabetes. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is hyperthyroidism. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is Cushing's syndrome. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is bacterial infection. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is sepsis. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is drug poisoning. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is heavy metal poisoning. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is burns. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is trauma. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is malignancy. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is cachexia. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is a side effect of chemotherapy. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is anorexia. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is rhabdomyolysis. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is chronic liver disease. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is acute-on-chronic liver disease. In some embodiments, the disease or condition associated with elevated urea levels in the subject's blood is ascites.

[0113] medicine box

[0114] In a fourth aspect, this disclosure provides a medicine box comprising: any of the pharmaceutical compositions described herein; at least one container for containing the pharmaceutical composition; and instructions for use and / or a pharmaceutical label.

[0115] In some implementations, the kit does not contain additional active ingredients.

[0116] In some embodiments, the pillbox includes at least one container for containing the pharmaceutical composition. In some embodiments, the pillbox includes one, two, three, or more containers. In some embodiments, the container is selected from blister packs, tubes, bottles, pumps, bags, tubular vials, syringes, cartons, and other containers.

[0117] In some implementations, the drug package insert and / or drug label include instructions for use, clinical trial results and discussion of results, a list of side effects, drug interactions, and / or additional information useful to healthcare providers, such as references.

[0118] Methods for managing conditions related to inappropriately elevated ammonia and / or ammonium ion levels in the blood and / or gastrointestinal tract of subjects and related pharmaceutical uses.

[0119] In a fifth aspect, this disclosure provides a method for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4) above, the method comprising administering to a subject in need a compound of formula I or a pharmaceutical composition comprising a compound of formula I and optionally one or more pharmaceutically acceptable excipients. In this respect, this disclosure also provides the use of a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients in the preparation of a medicine for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) the use of two or more of the above (1) to (4) in a pharmaceutical medicament.

[0120] In some embodiments, the method is a method for preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the method is a method for reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the method is a method for absorbing ammonia and / or ammonium ions from the digestive tract of a subject. In some embodiments, the method is a method for maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the method comprises two, three, or four methods for preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, absorbing ammonia and / or ammonium ions from the digestive tract of a subject, and maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject.

[0121] In some embodiments, the drug is a medicine for preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the drug is a medicine for lowering levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the drug is a medicine for absorbing ammonia and / or ammonium ions in the digestive tract of a subject. In some embodiments, the drug is a medicine for maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject. In some embodiments, the drug is a medicine comprising two, three, or four functions: preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, lowering levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject, absorbing ammonia and / or ammonium ions in the digestive tract of a subject, and maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject.

[0122] In some embodiments, the active ingredient of the pharmaceutical composition consists of a compound of formula I.

[0123] In some embodiments, the pharmaceutical composition is a unit dosage form.

[0124] In some embodiments, the unit dosage form comprises about 0.1 mg to about 200 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 150 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 100 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 50 g, for example, about 0.5 mg to about 25 g, about 1 mg to about 10 g, about 2 mg to about 5 g, or about 5 mg to about 1 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 50 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.5 mg to about 25 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 1 mg to about 10 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 2 mg to about 5 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 5 mg to about 1 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg, about 0.2 mg, about 0.25 mg, about 0.5 mg, about 0.75 mg, about 1 mg, about 2 mg, about 2.5 mg, about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 200 mg, about 250 mg, about 500 mg, about 750 mg, about 1 g, about 2 g, about 2.5 g, about 5 g, about 7.5 g, about 10 g, about 15 g, about 20 g, about 25 g, about 30 g, about 35 g, about 40 g. Compounds of Formula I in any amount of any subrange consisting of these point values, approximately 45 g, approximately 50 g, approximately 55 g, approximately 60 g, approximately 65 g, approximately 70 g, approximately 75 g, approximately 80 g, approximately 85 g, approximately 90 g, approximately 95 g, approximately 100 g, approximately 105 g, approximately 110 g, approximately 115 g, approximately 120 g, approximately 125 g, approximately 130 g, approximately 135 g, approximately 140 g, approximately 145 g, approximately 150 g, approximately 155 g, approximately 160 g, approximately 165 g, approximately 170 g, approximately 175 g, approximately 180 g, approximately 185 g, approximately 190 g, approximately 195 g, approximately 200 g, or any amount of the compound of Formula I.

[0125] In some embodiments, the unit dosage form comprises at least about 0.1 w / w%, such as about 0.1-99.9 w / w%, about 0.2-90 w / w%, about 0.25-80 w / w%, about 0.5-50 w / w%, about 0.75-25 w / w%, or about 1-10 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises at least about 0.1 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.1-99.9 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.2-90 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.25-80 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.5-50 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.75-25 w / w% of the compound of Formula I. In some embodiments, the unit dosage form comprises about 1-10 w / w% of the compound of Formula I. In some embodiments, the unit dosage form comprises about 0.1 w / w%, about 0.2 w / w%, about 0.25 w / w%, about 0.5 w / w%, about 0.75 w / w%, about 1 w / w%, about 2 w / w%, about 2.5 w / w%, about 5 w / w%, about 7.5 w / w%, about 10 w / w%, about 15 w / w%, about 20 w / w%, about 25 w / w%, etc. Compounds of Formula I in any amount of w%, about 30 w / w%, about 40 w / w%, about 50 w / w%, about 60 w / w%, about 70 w / w%, about 80 w / w%, about 90 w / w%, about 95 w / w%, about 99 w / w%, about 99.9 w / w%, about 99.99 w / w%, about 100 w / w%, or any amount of any subrange of these point values.

[0126] In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated as an oral formulation, optionally in unit dosage form. In some embodiments, the oral formulation is a solid oral formulation or a liquid oral formulation. In some embodiments, the oral formulation is a solid oral formulation. In some embodiments, the oral formulation is a liquid oral formulation. In some embodiments, the solid oral formulation is a powder, granules, tablets, capsules, pills, or lozenges. In some embodiments, the solid oral formulation is a powder. In some embodiments, the solid oral formulation is a granule. In some embodiments, the solid oral formulation is a tablet. In some embodiments, the solid oral formulation is a capsule. In some embodiments, the solid oral formulation is a pill. In some embodiments, the solid oral formulation is a lozenge. In some embodiments, the liquid oral formulation is a suspension. In some embodiments, the pharmaceutical composition is formulated for administration with or without food. In some embodiments, the pharmaceutical composition is formulated for administration without food. In some embodiments, "not administered with food" means administering the pharmaceutical composition at an interval of at least 30 minutes, at least 40 minutes, at least 50 minutes, at least 1 hour, at least 1.5 hours, at least 2 hours, or longer from food. In some embodiments, the pharmaceutical composition is formulated for administration with food. In some embodiments, "administered with food" means administering the pharmaceutical composition simultaneously with food or at an interval of at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, at most 15 minutes, at most 20 minutes, or at most 25 minutes.

[0127] In some embodiments, the pharmaceutical composition is formulated for rectal administration. In some embodiments, the pharmaceutical composition is formulated for administration by enema. In some embodiments, the pharmaceutical composition is formulated as a rectal-administered formulation, optionally in unit dosage form. In some embodiments, the rectal-administered formulation is a suppository, gel, paste, or enema. In some embodiments, the rectal-administered formulation is a suppository. In some embodiments, the rectal-administered formulation is a gel. In some embodiments, the rectal-administered formulation is a paste. In some embodiments, the rectal-administered formulation is an enema.

[0128] In some embodiments, the pharmaceutical composition is formulated for administration to the subject once, twice, three times, four times, or more daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject once daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject twice daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject three times daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject four times daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject more than four times daily. In some embodiments, the application lasts for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 10 months, at least 1 year, at least 1.5 years, at least 2 years, at least 2.5 years, at least 3 years, at least 4 years, at least 5 years, at least 10 years, or longer. In some embodiments, the application lasts for at least 1 day. In some embodiments, the application lasts for at least 2 days. In some embodiments, the application lasts for at least 3 days. In some embodiments, the application lasts for at least 4 days. In some embodiments, the application lasts for at least 5 days. In some embodiments, the application lasts for at least 6 days. In some embodiments, the application lasts for at least 1 week. In some embodiments, the application lasts for at least 2 weeks. In some embodiments, the application lasts for at least 3 weeks. In some embodiments, the application lasts for at least 1 month. In some embodiments, the application lasts for at least 2 months. In some embodiments, the application lasts for at least 3 months. In some embodiments, the application lasts for at least 4 months. In some embodiments, the application lasts for at least 5 months. In some embodiments, the application lasts for at least 6 months. In some embodiments, the application lasts for at least 8 months. In some embodiments, the application lasts for at least 10 months. In some embodiments, the application lasts for at least 1 year. In some embodiments, the application lasts for at least 1.5 years. In some embodiments, the application lasts for at least 2 years. In some embodiments, the application lasts for at least 2.5 years. In some embodiments, the application lasts for at least 3 years. In some embodiments, the application lasts for at least 4 years. In some embodiments, the application lasts for at least 5 years. In some embodiments, the application lasts for at least 10 years. In some embodiments, the application lasts for more than 10 years.

[0129] In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 2000 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 1500 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 1000 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day to about 500 mg / kg / day of the compound of formula I, for example, about 10 mg / kg / day to about 400 mg / kg / day of the compound of formula I, about 15 mg / kg / day to about 300 mg / kg / day of the compound of formula I, about 20 mg / kg / day to about 250 mg / kg / day of the compound of formula I, or about 25 mg / kg / day to about 225 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 500 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 10 mg / kg / day of the compound of formula I to about 400 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 15 mg / kg / day to about 300 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 20 mg / kg / day to about 250 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 25 mg / kg / day to about 225 mg / kg / day of the compound of formula I.In some embodiments, the pharmaceutical composition is formulated for use in doses of about or at least about 5 mg, about or at least about 10 mg, about or at least about 15 mg, about or at least about 20 mg, about or at least about 25 mg, about or at least about 30 mg, about or at least about 35 mg, about or at least about 40 mg, about or at least about 45 mg, about or at least about 50 mg, about or at least about 60 mg, about or at least about 70 mg, about or at least about 80 mg, about or at least about 90 mg, about or at least about 100 mg, about or at least about 120 mg, or about or at least about 1 mg. 40 mg, about or at least about 160 mg, about or at least about 180 mg, about or at least about 200 mg, about or at least about 220 mg, about or at least about 240 mg, about or at least about 260 mg, about or at least about 280 mg, about or at least about 300 mg, about or at least about 320 mg, about or at least about 340 mg, about or at least about 360 mg, about or at least about 380 mg, about or at least about 400 mg, about or at least about 420 mg, about or at least about 440 mg, about or at least about 460 mg, about or at least about 480 mg Approximately or at least 500 mg, approximately or at least 550 mg, approximately or at least 600 mg, approximately or at least 650 mg, approximately or at least 700 mg, approximately or at least 750 mg, approximately or at least 800 mg, approximately or at least 850 mg, approximately or at least 900 mg, approximately or at least 950 mg, approximately or at least 1000 mg, approximately or at least 1050 mg, approximately or at least 1100 mg, approximately or at least 1150 mg, approximately or at least 1200 mg, approximately or at least 1250 mg, approximately or at least 130 mg The subject was given a dose of 0 mg, or about or at least about 1350 mg, or about or at least about 1400 mg, or about or at least about 1450 mg, or about or at least about 1500 mg, or about or at least about 1550 mg, or about or at least about 1600 mg, or about or at least about 1650 mg, or about or at least about 1700 mg, or about or at least about 1750 mg, or about or at least about 1800 mg, or about or at least about 1850 mg, or about or at least about 1900 mg, or about or at least about 1950 mg, or about 2000 mg of a compound of Formula I per kg per day.

[0130] Methods for managing conditions related to inappropriately elevated urea levels in the blood and / or gastrointestinal tract of subjects and related pharmaceutical uses.

[0131] In a sixth aspect, this disclosure provides a method for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) two or more of the above (1) to (4), said method comprising administering to a subject in need a compound of formula I or a pharmaceutical composition comprising a compound of formula I and optionally one or more pharmaceutically acceptable excipients. In this respect, this disclosure also provides the use of a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and optionally one or more pharmaceutically acceptable excipients in the preparation of a pharmaceutical composition for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) the use of two or more of the above (1) to (4) in a pharmaceutical composition.

[0132] In some embodiments, the method is a method for reducing the level of urea or blood urea nitrogen (BUN) in a subject's blood. In some embodiments, the method is a method for reducing the level of urea in the digestive tract contents of a subject. In some embodiments, the method is a method for maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject. In some embodiments, the method is a method for preventing and / or treating a disease or condition associated with elevated urea levels in the subject's blood. In some embodiments, the method is a method for reducing the level of urea or blood urea nitrogen (BUN) in the subject's blood, reducing the level of urea in the digestive tract contents of the subject, maintaining an appropriate level of urea or blood urea nitrogen in the subject's blood, and preventing and / or treating two, three, or four of the following: reducing the level of urea or blood urea nitrogen (BUN) in the subject's blood, reducing the level of urea in the digestive tract contents of the subject, maintaining an appropriate level of urea or blood urea nitrogen in the subject's blood, and preventing and / or treating a disease or condition associated with elevated urea levels in the subject's blood.

[0133] In some embodiments, the drug is a drug for lowering the level of urea or blood urea nitrogen (BUN) in a subject's blood. In some embodiments, the drug is a drug for lowering the level of urea in the gastrointestinal contents of a subject. In some embodiments, the drug is a drug for maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject. In some embodiments, the drug is a drug for preventing and / or treating a disease or condition associated with elevated urea levels in the subject's blood. In some embodiments, the drug is a drug for lowering the level of urea or blood urea nitrogen (BUN) in a subject's blood, lowering the level of urea in the gastrointestinal contents of a subject, maintaining an appropriate level of urea or blood urea nitrogen in the subject's blood, and preventing and / or treating two, three, or four of the following:

[0134] In some embodiments, the active ingredient of the pharmaceutical composition consists of a compound of formula I.

[0135] In some embodiments, the pharmaceutical composition is a unit dosage form.

[0136] In some embodiments, the unit dosage form comprises about 0.1 mg to about 200 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 150 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 100 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 50 g, for example, about 0.5 mg to about 25 g, about 1 mg to about 10 g, about 2 mg to about 5 g, or about 5 mg to about 1 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg to about 50 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.5 mg to about 25 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 1 mg to about 10 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 2 mg to about 5 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 5 mg to about 1 g of the compound of formula I. In some embodiments, the unit dosage form comprises about 0.1 mg, about 0.2 mg, about 0.25 mg, about 0.5 mg, about 0.75 mg, about 1 mg, about 2 mg, about 2.5 mg, about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 200 mg, about 250 mg, about 500 mg, about 750 mg, about 1 g, about 2 g, about 2.5 g, about 5 g, about 7.5 g, about 10 g, about 15 g, about 20 g, about 25 g, about 30 g, about 35 g, about 40 g. Compounds of Formula I in any amount of any subrange consisting of these point values, approximately 45 g, approximately 50 g, approximately 55 g, approximately 60 g, approximately 65 g, approximately 70 g, approximately 75 g, approximately 80 g, approximately 85 g, approximately 90 g, approximately 95 g, approximately 100 g, approximately 105 g, approximately 110 g, approximately 115 g, approximately 120 g, approximately 125 g, approximately 130 g, approximately 135 g, approximately 140 g, approximately 145 g, approximately 150 g, approximately 155 g, approximately 160 g, approximately 165 g, approximately 170 g, approximately 175 g, approximately 180 g, approximately 185 g, approximately 190 g, approximately 195 g, approximately 200 g, or any amount of the compound of Formula I.

[0137] In some embodiments, the unit dosage form comprises at least about 0.1 w / w%, such as about 0.1-99.9 w / w%, about 0.2-90 w / w%, about 0.25-80 w / w%, about 0.5-50 w / w%, about 0.75-25 w / w%, or about 1-10 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises at least about 0.1 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.1-99.9 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.2-90 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.25-80 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.5-50 w / w% of a compound of Formula I. In some embodiments, the unit dosage form comprises about 0.75-25 w / w% of the compound of Formula I. In some embodiments, the unit dosage form comprises about 1-10 w / w% of the compound of Formula I. In some embodiments, the unit dosage form comprises about 0.1 w / w%, about 0.2 w / w%, about 0.25 w / w%, about 0.5 w / w%, about 0.75 w / w%, about 1 w / w%, about 2 w / w%, about 2.5 w / w%, about 5 w / w%, about 7.5 w / w%, about 10 w / w%, about 15 w / w%, about 20 w / w%, about 25 w / w%, etc. Compounds of Formula I in any amount of w%, about 30 w / w%, about 40 w / w%, about 50 w / w%, about 60 w / w%, about 70 w / w%, about 80 w / w%, about 90 w / w%, about 95 w / w%, about 99 w / w%, about 99.9 w / w%, about 99.99 w / w%, about 100 w / w%, or any amount of any subrange of these point values.

[0138] In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated as an oral formulation, optionally in unit dosage form. In some embodiments, the oral formulation is a solid oral formulation or a liquid oral formulation. In some embodiments, the oral formulation is a solid oral formulation. In some embodiments, the oral formulation is a liquid oral formulation. In some embodiments, the solid oral formulation is a powder, granules, tablets, capsules, pills, or lozenges. In some embodiments, the solid oral formulation is a powder. In some embodiments, the solid oral formulation is a granule. In some embodiments, the solid oral formulation is a tablet. In some embodiments, the solid oral formulation is a capsule. In some embodiments, the solid oral formulation is a pill. In some embodiments, the solid oral formulation is a lozenge. In some embodiments, the liquid oral formulation is a suspension. In some embodiments, the pharmaceutical composition is formulated for administration with or without food. In some embodiments, the pharmaceutical composition is formulated for administration without food. In some embodiments, "not administered with food" means administering the pharmaceutical composition at an interval of at least 30 minutes, at least 40 minutes, at least 50 minutes, at least 1 hour, at least 1.5 hours, at least 2 hours, or longer from food. In some embodiments, the pharmaceutical composition is formulated for administration with food. In some embodiments, "administered with food" means administering the pharmaceutical composition simultaneously with food or at an interval of at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, at most 15 minutes, at most 20 minutes, or at most 25 minutes.

[0139] In some embodiments, the pharmaceutical composition is formulated for rectal administration. In some embodiments, the pharmaceutical composition is formulated for administration by enema. In some embodiments, the pharmaceutical composition is formulated as a rectal-administered formulation, optionally in unit dosage form. In some embodiments, the rectal-administered formulation is a suppository, gel, paste, or enema. In some embodiments, the rectal-administered formulation is a suppository. In some embodiments, the rectal-administered formulation is a gel. In some embodiments, the rectal-administered formulation is a paste. In some embodiments, the rectal-administered formulation is an enema.

[0140] In some embodiments, the pharmaceutical composition is formulated for administration to the subject once, twice, three times, four times, or more daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject once daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject twice daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject three times daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject four times daily. In some embodiments, the pharmaceutical composition is formulated for administration to the subject more than four times daily. In some embodiments, the application lasts for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 10 months, at least 1 year, at least 1.5 years, at least 2 years, at least 2.5 years, at least 3 years, at least 4 years, at least 5 years, at least 10 years, or longer. In some embodiments, the application lasts for at least 1 day. In some embodiments, the application lasts for at least 2 days. In some embodiments, the application lasts for at least 3 days. In some embodiments, the application lasts for at least 4 days. In some embodiments, the application lasts for at least 5 days. In some embodiments, the application lasts for at least 6 days. In some embodiments, the application lasts for at least 1 week. In some embodiments, the application lasts for at least 2 weeks. In some embodiments, the application lasts for at least 3 weeks. In some embodiments, the application lasts for at least 1 month. In some embodiments, the application lasts for at least 2 months. In some embodiments, the application lasts for at least 3 months. In some embodiments, the application lasts for at least 4 months. In some embodiments, the application lasts for at least 5 months. In some embodiments, the application lasts for at least 6 months. In some embodiments, the application lasts for at least 8 months. In some embodiments, the application lasts for at least 10 months. In some embodiments, the application lasts for at least 1 year. In some embodiments, the application lasts for at least 1.5 years. In some embodiments, the application lasts for at least 2 years. In some embodiments, the application lasts for at least 2.5 years. In some embodiments, the application lasts for at least 3 years. In some embodiments, the application lasts for at least 4 years. In some embodiments, the application lasts for at least 5 years. In some embodiments, the application lasts for at least 10 years. In some embodiments, the application lasts for more than 10 years.

[0141] In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 2000 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 1500 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 1000 mg / kg / day. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day to about 500 mg / kg / day of the compound of formula I, for example, about 10 mg / kg / day to about 400 mg / kg / day of the compound of formula I, about 15 mg / kg / day to about 300 mg / kg / day of the compound of formula I, about 20 mg / kg / day to about 250 mg / kg / day of the compound of formula I, or about 25 mg / kg / day to about 225 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg / kg / day of the compound of formula I to about 500 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 10 mg / kg / day of the compound of formula I to about 400 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 15 mg / kg / day to about 300 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 20 mg / kg / day to about 250 mg / kg / day of the compound of formula I. In some embodiments, the pharmaceutical composition is formulated for administration to the subject at a dose of about 25 mg / kg / day to about 225 mg / kg / day of the compound of formula I.In some embodiments, the pharmaceutical composition is formulated for use in doses of about or at least about 5 mg, about or at least about 10 mg, about or at least about 15 mg, about or at least about 20 mg, about or at least about 25 mg, about or at least about 30 mg, about or at least about 35 mg, about or at least about 40 mg, about or at least about 45 mg, about or at least about 50 mg, about or at least about 60 mg, about or at least about 70 mg, about or at least about 80 mg, about or at least about 90 mg, about or at least about 100 mg, about or at least about 120 mg, or about or at least about 1 mg. 40 mg, about or at least about 160 mg, about or at least about 180 mg, about or at least about 200 mg, about or at least about 220 mg, about or at least about 240 mg, about or at least about 260 mg, about or at least about 280 mg, about or at least about 300 mg, about or at least about 320 mg, about or at least about 340 mg, about or at least about 360 mg, about or at least about 380 mg, about or at least about 400 mg, about or at least about 420 mg, about or at least about 440 mg, about or at least about 460 mg, about or at least about 480 mg Approximately or at least 500 mg, approximately or at least 550 mg, approximately or at least 600 mg, approximately or at least 650 mg, approximately or at least 700 mg, approximately or at least 750 mg, approximately or at least 800 mg, approximately or at least 850 mg, approximately or at least 900 mg, approximately or at least 950 mg, approximately or at least 1000 mg, approximately or at least 1050 mg, approximately or at least 1100 mg, approximately or at least 1150 mg, approximately or at least 1200 mg, approximately or at least 1250 mg, approximately or at least 130 mg The subject was given a dose of 0 mg, or about or at least about 1350 mg, or about or at least about 1400 mg, or about or at least about 1450 mg, or about or at least about 1500 mg, or about or at least about 1550 mg, or about or at least about 1600 mg, or about or at least about 1650 mg, or about or at least about 1700 mg, or about or at least about 1750 mg, or about or at least about 1800 mg, or about or at least about 1850 mg, or about or at least about 1900 mg, or about or at least about 1950 mg, or about 2000 mg of a compound of Formula I per kg per day.

[0142] Without causing conflict, the features of the various embodiments described in the foregoing aspects of this disclosure may be combined to obtain one or more other embodiments covered within the spirit and / or scope of this disclosure.

[0143] Example

[0144] The present disclosure is further described in detail below with reference to embodiments. Obviously, the described embodiments are only a part of, and not all of, the invention disclosed herein. These embodiments are for illustrative purposes only and should not be construed as limiting the scope of protection of the present invention. Based on the disclosed embodiments, all equivalent or similar technical solutions obtained by those skilled in the art without inventive effort fall within the scope of protection of the present invention.

[0145] Experimental materials

[0146] Magnesium phosphate pentahydrate (magnesium phosphate pentahydrate) was purchased from Shanghai Ennama Biotechnology Co., Ltd., 250g, 99% purity. Phosphoric acid was purchased from Greater, 500mL, 85% purity. Sodium hydroxide was purchased from Greater, 500g, ≥98% purity. Potassium hydroxide was purchased from Admas, 100g, 99.999% purity. Ammonia water was purchased from Admas, mL, 29% purity. Anhydrous sodium phosphate was purchased from Greater, 500g, ≥97.0% purity. Ammonium chloride (NH4Cl) was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g, 99.5% purity. Potassium chloride was purchased from Admas, 25g, 99.99% purity. Sodium chloride was purchased from Admas, 100g, 99.999% purity. Potassium dihydrogen phosphate was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g, 99% purity. Concentrated hydrochloric acid was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g specification, analytical grade. Dipotassium hydrogen phosphate was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g specification, 99% purity. Methyl ester sulfonate (MES) was purchased from Bid Pharmaceutical Co., Ltd., 50g specification, 99.6% purity. Sodium acetate was purchased from Sinopharm Chemical Reagent Co., Ltd., 100g specification, 98% purity. Sodium chloride was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g specification, 99% purity. Sodium citrate was purchased from Anaiji Chemical Reagent Co., Ltd., 50g specification, 99.8% purity. Oleic acid was purchased from Sinopharm Chemical Reagent Co., Ltd., 50g specification, 99.6% purity. Sodium taurocholate was purchased from Sinopharm Chemical Reagent Co., Ltd., 25g specification, 99.5% purity. Lecithin was purchased from Shanghai Ennama Biotechnology Co., Ltd., 25g specification, 99.5% purity. Acetic acid was purchased from Sinopharm Chemical Reagent Co., Ltd., 500g specification, analytical grade. Maleic acid was purchased from Shanghai Ennama Biotechnology Co., Ltd., 50g, 99% purity. Sodium cholate was purchased from Anaiji Chemical Reagent Co., Ltd., 50g, 99.5% purity. Sodium oleate was purchased from Anaiji Chemical Reagent Co., Ltd., 25g, 99.6% purity. TRIS was purchased from Anaiji Chemical Reagent Co., Ltd., 100g, 99% purity. All other substances, unless otherwise specified, were commercially available or readily prepared by those skilled in the art using conventional techniques based on commercially available substances.

[0147] Example 1: Synthesis and structural characterization of samples of compounds of Formula I

[0148] Synthesis method: Samples of compounds of formula I described herein (where M is Na) +Magnesium phosphate (Mg3(PO4)2·5H2O) can be synthesized using the following method. Specifically, a certain amount of phosphoric acid (H3PO4) is added to an aqueous suspension containing a certain amount of magnesium phosphate pentahydrate (Mg3(PO4)2·5H2O). After high-speed stirring for 5-30 minutes, a certain amount of sodium hydroxide (NaOH) aqueous solution is added. The molar ratios of the feed substances, including phosphoric acid, magnesium phosphate pentahydrate, and sodium hydroxide, are shown in Table 1 below. The mixture is then stirred at high speed for another 5-30 minutes and allowed to stand for a period of time until the crude product is formed. A certain amount of pure water is added to the crude product (the volume ratio of crude product to pure water is 1 mL of crude product / 2 mL of water; alternatively, the volume ratio can also be 1 mL of crude product / 4 mL of water, 1 mL of crude product / 8 mL of water, 1 mL of crude product / 16 mL of water, 1 mL of crude product / 32 mL of water, etc., and when the volume of pure water used for washing increases, the number of washing cycles can be reduced accordingly to achieve a similar washing effect), mixed evenly, centrifuged, and the supernatant is removed. The above washing steps are repeated 3 times. After drying, dried samples MgNaP1, MgNaP2, MgNaP3, and MgNaP4 are obtained. The washing steps for MgNaP2, MgNaP3, and MgNaP4 are increased to 10 times to obtain MgNaP5, MgNaP6, and MgNaP7, respectively.

[0149] Structural characterization: The elemental composition of the dried samples was determined by inductively coupled plasma mass spectrometry (ICP-MS), and the dehydration weight loss of the dried samples was determined by thermogravimetric analysis (TGA) to obtain the chemical composition of the samples (see Table 1 below). Powder X-ray diffraction (PXRD) was also used to determine the crystal form of the dried samples. MgNaP1, MgNaP2, MgNaP3, MgNaP4, MgNaP5, MgNaP6, and MgNaP7 all exhibited amorphous or weakly crystalline structures.

[0150] Table 1 shows the parameters used in the synthesis of the compounds of Formula I and the characterization of the dried samples.

[0151] Example 2: Determination of in vitro ammonia scavenging rate and ammonia absorption capacity of samples of compounds of Formula I

[0152] In this embodiment, the ammonia absorption capacity of different samples of the compound of formula I prepared in Example 1 was investigated in ammonium chloride solution (Note: the ammonia absorption capacity measured in the examples is actually the sum of the absorption capacities for both ammonia and ammonium ions). Furthermore, it is known that intestinal fluid contains high levels of cations such as sodium and potassium ions, which may interfere with the ammonia absorption performance of the absorbent material. Therefore, in this embodiment, the selective ammonia absorption capacity of different samples was also investigated in an aqueous solution containing a mixture of inorganic salts (ammonium chloride, potassium chloride, and sodium chloride) in addition to ammonium chloride. Finally, simulated fasting colonic fluid (FaSSCOF) and simulated eating colonic fluid (FeSSCOF) were also used in this embodiment to investigate the selective ammonia absorption capacity of different samples. In this paper, unless the context otherwise indicates otherwise, ammonia absorption capacity and / or ammonia scavenging rate are used as indicators reflecting the sample's ability to absorb ammonia. Ammonia absorption capacity is the number of millimoles of ammonia that can be absorbed per gram of sample, and ammonia scavenging rate is the percentage by which the sample reduces the ammonia concentration in an ammonia-containing aqueous solution. The specific calculation formulas are shown in Equations 1, 2, and 3: Ammonia absorption capacity = (Original ammonia concentration - Ammonia concentration after absorption) / Adsorbent concentration (Equation 1) Ammonia scavenging rate = (Original ammonia concentration - Ammonia concentration after absorption) / Original ammonia concentration * 100% (Equation 2) Ammonia absorption capacity = Ammonia scavenging rate * Original ammonia concentration / Adsorbent concentration (Equation 3)

[0153] The original ammonia concentration and the ammonia concentration after absorption are in mmol / L, and the adsorbent concentration is in g / L.

[0154] Experimental Methods: Six different ammonia-containing solutions were prepared as shown in Table 2. 50 mg of each of the different samples of the compound of formula I prepared in Example 1 were weighed and added to 15 mL centrifuge tubes. 10 mL of ammonia-containing solution was added to each centrifuge tube. The centrifuge tubes were placed horizontally on a shaker and shaken at 200 rpm for 24 hours at 37°C. After the shaking was complete, 1 mL was aspirated from each tube. After filtration through a filter membrane, the filtrate was analyzed with an ammonia nitrogen detection reagent, and the ammonia content in the solution was detected using an ELISA reader.

[0155] Table 2. Preparation methods for various ammonia-containing solutions

[0156] Experimental Results Analysis: The experimental results are shown in Table 3. The results in Table 3 indicate that, in a 10 mM ammonium chloride solution, various samples of the compound I exhibited varying degrees of ammonia scavenging effect. The ammonia scavenging rate or ammonia absorption capacity of various samples of the compound I in a mixed ionic solution containing 10 mM ammonium chloride decreased only slightly compared to an aqueous solution containing the same concentration of ammonium chloride. In simulated fasting colonic fluid (FaSSCOF) and simulated feeding colonic fluid (FeSSCOF) containing 10 mM ammonium chloride, the ammonia scavenging rate or ammonia absorption capacity of various samples of the compound I remained at a high level. For example, MgNaP6 showed an ammonia scavenging rate of 35% and an ammonia absorption capacity of 0.70 mmol / g in ammonia-containing FaSSCOF, while MgNaP4 showed an ammonia scavenging rate of 62% and an ammonia absorption capacity of 1.24 mmol / g in ammonia-containing FeSSCOF, and so on. These results indicate that MgNaP2-7 possesses high ammonia scavenging capacity in different media solutions containing ammonium chloride.

[0157] Table 3 shows the ammonia scavenging rate and ammonia absorption capacity of different samples of compound I in different ammonia-containing solutions.

[0158] Example 3: In vivo experiment on the reduction of blood ammonia levels in healthy rats by a sample of compound I.

[0159] The purpose of this embodiment is to further investigate in vivo the effects of different samples of the compound of formula I prepared by Example 1 on blood ammonia levels and blood electrolytes in healthy rats. Specifically, this embodiment investigates the effect of the compound of formula I sample MgNaP1-4 on reducing blood ammonia levels and its effects on blood magnesium, blood phosphorus, and blood sodium in healthy rats.

[0160] Experimental Methods: Male SD rats aged 6–8 weeks were randomly divided into five groups, named control group, MgNaP1 group, MgNaP2 group, MgNaP3 group, and MgNaP4 group. After at least 5 days of acclimatization, the rats were fasted for 12 hours overnight on Day 0 before drug administration, and their body weight was measured and recorded. On Day 1, each group of rats was administered the drug by gavage at a dose of 10 mL / kg body weight per rat per day. The specific grouping and administration methods were as follows:

[0161] (1) Control group: physiological saline was used for gavage.

[0162] (2) MgNaP1 group: MgNaP1 (dosage: 300mg / kg body weight) was dispersed in physiological saline and administered by gavage.

[0163] (3) MgNaP2 group: MgNaP2 (dosage: 300mg / kg body weight) was dispersed in physiological saline and administered by gavage.

[0164] (4) MgNaP3 group: MgNaP3 (dosage: 300mg / kg body weight) was dispersed in physiological saline and administered by gavage.

[0165] (5) MgNaP4 group: MgNaP4 (dosage: 300mg / kg body weight) was dispersed in physiological saline and administered by gavage.

[0166] One hour after gavage, arterial blood (approximately 0.6 mL) was collected from each rat. The collected blood was placed in an anticoagulant blood collection tube, and the levels of blood ammonia, magnesium, phosphorus, and sodium were measured. The rats were then sacrificed, and cerebrospinal fluid was collected to test the ammonia level in the cerebrospinal fluid.

[0167] Experimental Results: The experimental results are shown in Table 4. The results in Table 4 indicate that the blood ammonia levels in the control group rats were at normal levels, while the blood ammonia levels in each of the drug-treated groups were lower than those in the control group to varying degrees. Table 4 also shows that the blood magnesium, phosphorus, and sodium levels in each drug-treated group were not significantly different from those in the control group. Table 4 further shows that the ammonia levels in the cerebrospinal fluid of each drug-treated group were lower than those in the control group to varying degrees. In summary, oral administration of compound I can effectively reduce blood ammonia levels and cerebrospinal fluid ammonia levels in rats, with almost no effect on the levels of electrolytes such as magnesium, phosphorus, and sodium in the blood.

[0168] Table 4. Effects of different samples of Formula I compounds administered orally on serum ammonia, magnesium, phosphorus, and sodium levels in healthy rats.

[0169] Example 4: In vivo experiment on the reduction of blood ammonia and blood urea levels in a nephrectomy model rat by a sample of compound I.

[0170] The purpose of this embodiment is to further investigate the effects of different samples of the compound of formula I prepared by Example 1 on blood ammonia and blood urea nitrogen levels in rats with renal insufficiency in vivo. Specifically, this embodiment investigates the effect of the sample MgNaP2-4 of compound of formula I on reducing blood ammonia and blood urea nitrogen (BUN) levels in a 5 / 6 nephrectomy rat model.

[0171] Modeling method: Male SD rats aged 6-8 weeks were used. After one week of acclimatization, the SD rats underwent their first surgery to remove one kidney. After two weeks of recovery, the SD rats underwent a second surgery to remove two-thirds of the other kidney. After two weeks of recovery, the surgical model was completed, resulting in 5 / 6 nephrectomy SD rats. Rats of similar weight and in good condition were selected for the formal experiment.

[0172] Experimental Methods: Normal SD rats and 5 / 6 nephrectomy SD rats were divided into five groups, named normal group, blank control group, MgNaP2 group, MgNaP3 group, and MgNaP4 group. Rats in each group underwent a 7-day acclimatization period (from day 1 to day 7). The drug administration experiment began the day after the acclimatization period ended (from day 8 to day 10). Specifically, from day 8 to day 10, the normal group and blank control group received physiological saline via gavage three times daily (gavage volume: 5 ml / kg body weight), while the other groups received the corresponding MgNaP suspension in physiological saline via gavage three times daily (dosage: 1000 mg / kg body weight, gavage volume: 5 ml / kg body weight). Rats were fasted for 12 hours on the evenings of day 7, 8, and 10 until blood collection the following day. Blood samples were collected from the orbital rims of all rats on the morning of day 8, the morning of day 9, and the morning of day 11 before administration to test blood ammonia and blood urea nitrogen (BUN) levels.

[0173] Experimental Results: The results of blood ammonia and blood urea nitrogen levels in each group of rats are shown in Table 5. The results in Table 5 indicate that, compared with normal SD rats, the blood ammonia and blood urea nitrogen levels in 5 / 6 nephrectomy SD rats were significantly increased. Gavage administration of MgNaP2-4 not only significantly reduced blood ammonia levels in 5 / 6 nephrectomy SD rats, but also significantly reduced blood urea nitrogen (BUN) levels in these rats.

[0174] Table 5. Effects of different samples of Formula I compounds administered orally on serum ammonia and blood urea nitrogen levels in rats with renal insufficiency.

[0175] Based on the above results, it can be found that oral administration of the compound of formula I can effectively reduce the blood ammonia level and blood urea nitrogen level in the experimental animals used.

[0176] Example 5: Synthesis of another sample of the compound of formula I

[0177] Synthetic method: Another sample of the compound of formula I described herein (where M is K) +Magnesium phosphate (Mg3(PO4)2·5H2O) can be synthesized using the following method. Specifically, a certain amount of phosphoric acid (H3PO4) is added to an aqueous suspension containing a certain amount of magnesium phosphate pentahydrate (Mg3(PO4)2·5H2O). After high-speed stirring for 5-30 minutes, a certain amount of potassium hydroxide (KOH) aqueous solution is added. The molar ratios of the feed substances, namely phosphoric acid, magnesium phosphate pentahydrate, and potassium hydroxide, are shown in Table 6 below. The mixture is then stirred at high speed for another 5-30 minutes and allowed to stand for a period of time until the crude product is formed. Add a certain amount of pure water to the crude product (the volume ratio of crude product to pure water is 1 mL of crude product / 2 mL of water; alternatively, the volume ratio can also be 1 mL of crude product / 4 mL of water, 1 mL of crude product / 8 mL of water, 1 mL of crude product / 16 mL of water, 1 mL of crude product / 32 mL of water, etc., and when the volume of pure water used for washing increases, the number of washing times can be reduced accordingly to achieve a similar washing effect), mix evenly, centrifuge, remove the supernatant, repeat the above washing steps 3 times, and dry to obtain dried samples MgKP1, MgKP2, MgKP3, MgKP4 and MgKP5.

[0178] Structural characterization: The elemental composition of the dried sample was determined by inductively coupled plasma mass spectrometry (ICP-MS), and the experimental method was the same as in Example 1.

[0179] Table 6 shows the parameters used in the synthesis of other samples of the compound of formula I and the elemental composition of the dried samples.

[0180] Example 6: Determination of in vitro ammonia scavenging rate and ammonia absorption capacity of another sample of the compound of formula I.

[0181] In this embodiment, different samples of the compound of formula I prepared by Example 5 (where M is K) were examined. + The ammonia absorption capacity of the sample in an ammonium chloride aqueous solution (Note: The ammonia absorption capacity measured in the examples is actually the sum of the absorption capacities of both ammonia and ammonium ions). Unless otherwise indicated by the context, ammonia absorption capacity and / or ammonia scavenging rate are used as indicators reflecting the sample's ammonia absorption capacity. Ammonia absorption capacity is the number of millimoles of ammonia that can be absorbed per gram of sample, and ammonia scavenging rate is the percentage by which the sample reduces the ammonia concentration in an ammonia-containing aqueous solution. Specific calculation formulas are given in Equations 1, 2, and 3 as described in Example 2.

[0182] Experimental Method: Prepare a 10 mM ammonium chloride aqueous solution as shown in Table 2 above. Weigh 50 mg each of different samples of the compound of formula I prepared in Example 5 and the reference sample magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O), and add them to 15 mL centrifuge tubes. Add 10 mL of 10 mM ammonium chloride aqueous solution to each centrifuge tube to make the sample concentration 5 mg sample / mL ammonium chloride aqueous solution. Place the centrifuge tubes flat on a shaker and shake at 200 rpm for 24 h at 37 °C. After the shaking is complete, aspirate 1 mL from each tube. After filtration through a filter membrane, the filtrate is treated with an ammonia nitrogen detection reagent and the ammonia content in the solution is detected using an ELISA reader.

[0183] Experimental Results Analysis: The experimental results are shown in Table 7. The results in Table 7 indicate that, compared with the preparation of M as described in Example 1, M is Na + Similar to the samples of compounds of formula I, M was prepared as described in Example 5, where K was the compound of formula I. + Another sample of the compound of formula I, MgKP1-5, also exhibits excellent ammonia scavenging effect in ammonia-containing aqueous solutions, and this ammonia scavenging effect is much greater than that of the reference substance magnesium hydrogen phosphate trihydrate under the same conditions.

[0184] Table 7 shows the ammonia scavenging rate and ammonia absorption capacity of different samples of compound I in 10 mM ammonium chloride aqueous solution at a sample concentration of 5 mg / mL.

[0185] Example 7: Determination of in vitro ammonia scavenging rate and ammonia absorption capacity of MgNaP3 under different ammonia adsorption conditions.

[0186] In this embodiment, the ammonia scavenging rate and ammonia absorption capacity of the MgNaP3 sample, a compound of formula I prepared as in Example 1, were further comprehensively evaluated under different ammonia adsorption conditions (adsorption time, sample concentration, ammonia-containing solution concentration, and various additives) to further comprehensively evaluate the ammonia absorption capacity of MgNaP3 (Note: the ammonia absorption capacity of the sample measured in the embodiment is actually the sum of the absorption capacities for both ammonia and ammonium ions). Specifically, the ammonia adsorption performance of MgNaP3 was examined in this embodiment under the following variables:

[0187] Adsorption time:

[0188] The adsorption rate of ammonia by MgNaP3 on ammonia-containing solution was investigated by measuring the residual ammonia concentration (mM) in the ammonia-containing solution at different time points (samples were taken at 0 h, 0.17 h, 0.5 h, 1 h, 2 h, and 24 h after mixing). 0 h refers to the ammonia concentration in the ammonia-containing solution obtained immediately after mixing MgNaP3 with the ammonia-containing solution.

[0189] Sample concentration of MgNaP3:

[0190] The ammonia adsorption performance of MgNaP3 at different concentrations (0.5 mg / mL, 1 mg / mL, 2 mg / mL, 5 mg / mL, and 10 mg / mL) was evaluated.

[0191] Ammonia solution concentration:

[0192] The adsorption performance of MgNaP3 on ammonia in ammonia solutions at different ammonia concentrations was investigated at concentrations of 5 mM, 10 mM, and 50 mM (Note: 5 mM, 10 mM, and 50 mM refer to the concentrations of ammonia in the solution).

[0193] Types of additives:

[0194] The adsorption performance of MgNaP3 on ammonia in ammonia-containing solutions was investigated under different additives, namely NaCl, NaHCO3, Na2SO4, Na2HPO4, KCl, MgCl2 and CaCl2.

[0195] Basic experimental method: As shown in Table 8, various ammonia-containing solutions, each containing a certain concentration of ammonium chloride (optionally also containing a certain concentration of additives), were prepared and added to multiple 15 mL centrifuge tubes. A certain mass of MgNaP3 prepared in Example 1 was weighed and added to each of the various ammonia-containing solutions to achieve the "sample concentrations" shown in Table 8. Then, each centrifuge tube was placed horizontally on a shaker and shaken at 200 rpm for 24 hours at 37°C. At the specified sampling time points, the sample solution was aspirated, filtered through a filter membrane, and the filtrate was colorimetrically analyzed with an ammonia nitrogen detection reagent and then the ammonia content in the sample solution was detected using an ELISA reader.

[0196] Experimental Results Analysis: The experimental results are shown in Table 8. The results in Table 8 show that MgNaP3 exhibits rapid adsorption capacity for ammonia in ammonia-containing solutions under various ammonia adsorption conditions: MgNaP3 adsorbs immediately after mixing with the ammonia-containing solution, reaching its maximum adsorption value within 0.17 h. Table 8 also shows that the ammonia absorption capacity of MgNaP3 in ammonia-containing solutions increases with increasing ammonia concentration. Furthermore, Table 8 indicates that MgNaP3 exhibits high ammonia adsorption performance in ammonia-containing solutions in the presence of various specified concentrations of additives. This demonstrates that MgNaP3 has high selectivity and specificity for ammonia adsorption in solution, and the presence of other inorganic salts in the solution does not substantially reduce the ammonia adsorption capacity of MgNaP3.

[0197] Table 8. Ammonia scavenging rate and ammonia absorption capacity of MgNaP3 under various ammonia adsorption conditions.

[0198] Example 8: In vivo experiment on the reduction of blood ammonia levels in rats with a thioacetamide (TAA)-induced hyperammonemia model of the compound of Formula I.

[0199] The purpose of this embodiment is to investigate the preventive and / or therapeutic effects of an exemplary compound of Formula I on hyperammonemia in animal models of hyperammonemia. Thioacetamide (TAA) is a toxic substance that can cause hepatocyte degeneration and necrosis, leading to acute liver injury and thereby inducing elevated blood ammonia levels. Therefore, in this embodiment, the effects of MgNaP3 and MgKP1, prepared according to Examples 1 and 5 respectively, on reducing blood ammonia levels in rats with TAA-induced hyperammonemia were investigated.

[0200] Experimental Methods: Male SD rats aged 6-8 weeks were randomly divided into three groups: blank control group, model group, MgNaP3 group, and MgKP1 group. Rats in each group underwent a 7-day acclimatization period (from day 1 to day 7). The modeling experiment was conducted for 2 days starting the day after the acclimatization period (from day 8 to day 9). Specifically, the blank control group received daily intraperitoneal injections of physiological saline (5 ml / kg body weight), while the other groups received daily intraperitoneal injections of TAA (250 mg / kg body weight, 5 ml / kg body weight). In parallel, daily administration was continued for 3 days starting the day after the acclimatization period (from day 8 to day 10). Rats in each group were administered the drug via gavage at a dose of 5 mL / kg body weight per rat per day. The specific grouping and administration methods were as follows:

[0201] (1) Blank control group: pure water was used for gavage.

[0202] (2) Model group: Pure water was used for gavage.

[0203] (3) MgNaP3 group: MgNaP3 (dosage: 150mg / kg body weight) suspension dispersed in pure water was used for gavage.

[0204] (4) MgKP1 group: MgKP1 (dosage: 150mg / kg body weight) suspension dispersed in pure water was used for gavage.

[0205] One hour after the last gavage, blood was collected from the orbital cavity of all rats to prepare plasma and test blood ammonia levels.

[0206] Experimental Results: The blood ammonia levels of rats in each group are shown in Table 9. The results in Table 9 indicate that, under the induction of thioacetamide, the blood ammonia level in the model group was significantly higher than that in the blank control group, suggesting successful model establishment. Table 9 also shows that the blood ammonia levels in the MgNaP3 group or the MgKP1 group were significantly lower than those in the model group, and even lower than those in the blank control group. In summary, these results demonstrate that oral administration of compound I can effectively reduce blood ammonia levels in rats.

[0207] Table 9. Effects of different samples of oral administration of Formula I compounds on serum ammonia levels in TAA-induced hyperammonemia model rats.

Claims

A compound of formula I: Mg3(PO4 3- ) a M b (HPO4 2- ) c (OH) d I in M is selected from alkali metal ions, ammonium ions, or any combination thereof; a≥1.5； b＞0； c≥0； d≥0； When a < 2, c < 0.

4. The compound according to claim 1, wherein M is selected from Li + Na + K + NH4 + Or any combination thereof. The compound according to claim 1 or 2, wherein M is selected from Li + Na + Or any combination thereof. The compound according to any one of claims 1-3, wherein M is selected from K. + Na + Or any combination thereof. The compound according to any one of claims 1-4, wherein M is Na + or K + . The compound according to any one of claims 1-5, wherein 1.7 ≤ a ≤ 6. The compound according to any one of claims 1-6, wherein 2 ≤ a ≤ 4. The compound according to any one of claims 1-7, wherein 2 ≤ a ≤ 3.

5. The compound according to any one of claims 1-8, wherein 0.4 ≤ b ≤ 6. The compound according to any one of claims 1-9, wherein 0.5 ≤ b ≤ 4. The compound according to any one of claims 1-10, wherein 0.6 ≤ b ≤ 3.

5. The compound according to any one of claims 1-11, wherein 0 ≤ c ≤ 2. The compound according to any one of claims 1-12, wherein 0.1 ≤ c ≤ 1.

5. The compound according to any one of claims 1-13, wherein 0.2 ≤ c ≤ 1.

4. The compound according to any one of claims 1-14, wherein 0 ≤ d ≤ 2. The compound according to any one of claims 1-15, wherein 0.2 ≤ d ≤ 1.

8. The compound according to any one of claims 1-16, wherein 0.4 ≤ d ≤ 1.

6. The compound according to any one of claims 1-17, wherein 0.5 ≤ (a+c) / 3 ≤ 3.

5. The compound according to any one of claims 1-18, wherein 0.55 ≤ (a+c) / 3 ≤ 2. The compound according to any one of claims 1-19, wherein 0.6 ≤ (a+c) / 3 ≤ 1.

5. The compound according to any one of claims 1-20, wherein the compound of formula I is an amorphous product. The compound according to any one of claims 1-21, wherein the compound of formula I is in crystalline form. The compound according to any one of claims 1-22, wherein the compound of formula I contains a total of ≤30 w / w% or ≤25 w / w% water. The compound according to any one of claims 1-23, wherein the compound of formula I contains a total of ≤20 w / w% water. The compound according to any one of claims 1-24, wherein the compound of formula I contains a total of ≤17.5 w / w%, ≤15 w / w%, or ≤12.5 w / w% water. The compound according to any one of claims 1-25, wherein the compound of formula I is in a non-gel solid form. The compound according to any one of claims 1-26, wherein the compound of formula I is in the form of a sheet-like solid. The compound according to any one of claims 1-27, wherein the compound of formula I is non-thixotropic. The compound according to any one of claims 1-28, wherein the compound of formula I is orally nonabsorbable or substantially nonabsorbable. The compound according to any one of claims 1-29, wherein when placed in an aqueous environment, the compound of formula I absorbs ammonia and / or ammonium ions from the aqueous environment. The compound according to any one of claims 1-30, wherein the compound of formula I has a scavenging rate of ammonia and / or ammonium ions of ≥ 50% and / or an ammonia absorption capacity of ≥ 1 mmol / g in water containing about 10 mM of ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-31, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥ 70% and / or an ammonia absorption capacity of ≥ 1.5 mmol / g in water containing about 10 mM of ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-32, wherein the compound of formula I has a scavenging rate of ammonia and / or ammonium ions of ≥90% and / or an ammonia absorption capacity of ≥1.8 mmol / g in water containing about 10 mM of ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-33, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥40% and / or an ammonia absorption capacity of ≥0.8 mmol / g, as measured in an aqueous solution of a mixed inorganic salt containing about 10 mM ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-34, wherein the aqueous solution of the mixed inorganic salt is an aqueous solution containing an alkali metal halide in addition to ammonia and / or ammonium ions. The compound according to any one of claims 1-35, wherein the aqueous solution of the mixed inorganic salt is an aqueous solution of sodium halide, potassium halide and ammonium halide. The compound according to any one of claims 1-36, wherein the aqueous solution of the mixed inorganic salt is an aqueous solution of sodium chloride, potassium chloride and ammonium chloride. The compound according to any one of claims 1-37, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥30% and / or an ammonia absorption capacity of ≥0.5 mmol / g in FaSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-38, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥30% and / or an ammonia absorption capacity of ≥0.6 mmol / g in FeSSCOF containing about 10 mM ammonia and / or ammonium ions within about 24 h. The compound according to any one of claims 1-39, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥60% and / or an ammonia absorption capacity of ≥1.3 mmol / g, as measured in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, within about 24 h. The compound according to any one of claims 1-40, wherein the compound of formula I has a scavenging capacity of ammonia and / or ammonium ions of ≥ 70% and / or an ammonia absorption capacity of ≥ 1.5 mmol / g, as measured in an aqueous solution containing about 10 mM ammonia and / or ammonium ions and additives, within about 24 h. The compound according to any one of claims 1-41, wherein the additive is selected from alkali metal halides, alkali metal carbonates, alkali metal bicarbonates, alkali metal sulfates, alkali metal bisulfates, alkali metal phosphates, alkali metal hydrogen phosphates, alkali metal dihydrogen phosphates, alkaline earth metal halides, alkaline earth metal carbonates, alkaline earth metal bicarbonates, alkaline earth metal sulfates, alkaline earth metal bisulfates, alkaline earth metal phosphates, alkaline earth metal hydrogen phosphates, and alkaline earth metal dihydrogen phosphates, provided that the additive is readily soluble in water or soluble in water. The compound according to any one of claims 1-42, wherein the additive is selected from (a) chlorides or bromides of sodium, potassium, magnesium or calcium, (b) bicarbonates of sodium, potassium, magnesium or calcium, (c) sulfates of sodium, potassium, magnesium or calcium, and (d) hydrogen phosphates of sodium, potassium, magnesium or calcium, provided that the additive is readily soluble in water or soluble in water. The compound according to any one of claims 1-43, wherein the additive is selected from NaCl, NaHCO3, Na2SO4, Na2HPO4, KCl, MgCl2 and CaCl2. The compound according to any one of claims 1-44, wherein the concentration of the additive in the aqueous solution is from about 10 mM to about 150 mM. The compound according to any one of claims 1-45, wherein the scavenging rate of the compound of formula I for ammonia and / or ammonium ions is measured at about 37°C, about 1 standard atmosphere, under oscillation conditions, and with a mass-to-volume ratio of the compound of formula I to the liquid medium of 5 mg of the compound of formula I / 1 mL of liquid medium. The compound according to any one of claims 1-46, wherein when placed in an aqueous environment, the compound of formula I selectively absorbs ammonia and / or ammonium ions relative to other cations also present in the aqueous environment. The compound according to any one of claims 1-47, wherein the other cation is a potassium ion or a sodium ion. The compound according to any one of claims 1-48, wherein when administered orally to a subject, the compound of formula I reduces the level of urea in the subject's blood and / or digestive tract. The compound according to any one of claims 1-49, wherein the compound of formula I is prepared by a method comprising the steps of: mixing phosphoric acid and magnesium phosphate pentahydrate in water and stirring to obtain a mixture A; adding MOH or an aqueous solution thereof to mixture A and stirring to obtain a mixture B; allowing mixture B to stand and age for a period of time to obtain a crude product; washing the crude product with water to remove soluble substances to obtain the compound of formula I, wherein the MOH is an alkali metal hydroxide, ammonium hydroxide, or any combination thereof. The compound according to any one of claims 1-50, wherein the molar ratio of magnesium phosphate pentahydrate, phosphoric acid and MOH is 1:1.5-9:3-21. The compound according to any one of claims 1-51, wherein the molar ratio of magnesium phosphate pentahydrate, phosphoric acid and MOH is 1:1.5-9:3-18. The compound according to any one of claims 1-52, wherein the molar ratio of magnesium phosphate pentahydrate, phosphoric acid and MOH is 1:3:9, 1:9:18, 1:2:5, 1:1.5:3 or 1:6:

21. The compound according to any one of claims 1-53, wherein the stirring lasts for at least 3 minutes. The compound according to any one of claims 1-54, wherein the stirring lasts for 5-30 minutes. The compound according to any one of claims 1-55, wherein the MOH is LiOH, NaOH, KOH, NH4OH or any combination thereof. The compound according to any one of claims 1-56, wherein the MOH is LiOH, NaOH, or any combination thereof. The compound according to any one of claims 1-57, wherein the MOH is NaOH, KOH or any combination thereof. The compound according to any one of claims 1-58, wherein the MOH is NaOH. The compound according to any one of claims 1-59, wherein the MOH is KOH. The compound according to any one of claims 1-60, wherein the static aging lasts for at least 1 minute. The compound according to any one of claims 1-61, wherein the static aging lasts for at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 1.5 hours, or at least 2 hours. The compound according to any one of claims 1-62, wherein the crude product is washed with water as follows: the crude product is mixed with water until homogeneous, centrifuged, the supernatant is removed, and optionally the above washing steps are repeated once or more. The compound according to any one of claims 1-63, wherein the volume / volume ratio of the crude product mixed with water is from 1 mL of the crude product / 2 mL of water to 1 mL of the crude product / 32 mL of water. The compound according to any one of claims 1-64, wherein the washing steps 2, 3, 4, 5, 6, 7, 8, 9 or 10 are repeated. The compound according to any one of claims 1-65, wherein the method further comprises drying the compound of formula I to obtain the compound of formula I in a dried state. The compound according to any one of claims 1-66, wherein the compound of formula I has the chemical formula: Mg3(PO4) 3- )2Na 1.6 (HPO4 2- )0(OH) 1.6 Mg3(PO4) 3- )2Na 2.8 (HPO4 2- ) 1.4 (OH)0, Mg3(PO4) 3- ) 3.1 Na 3.7 (HPO4 2- )0(OH) 0.4 Mg3(PO4) 3- )2Na 2.4 (HPO4 2- ) 1.2 (OH)0, Mg3(PO4) 3- ) 2.2 Na 0.8 (HPO4 2- ) 0.1 (OH)0, Mg3(PO4) 3- )2Na 0.4 (HPO4 2- ) 0.2 (OH)0 or Mg3(PO4) 3- ) 1.7 Na 0.5 (HPO4 2- )0(OH) 1.4 . A method for preparing a compound of formula I according to any one of claims 1-67, comprising the following steps: Mixture A is obtained by mixing phosphoric acid and magnesium phosphate pentahydrate in water and stirring. Adding MOH or an aqueous solution thereof to mixture A and stirring the mixture yields mixture B; The mixture B was left to stand and age for a period of time to obtain a crude product; The crude product is washed with water to remove soluble substances, yielding a compound of formula I, wherein the MOH is an alkali metal hydroxide, ammonium hydroxide, or any combination thereof. According to the method of claim 68, the molar ratio of magnesium phosphate pentahydrate, phosphoric acid, and MOH is 1:1.5-9:3-21. According to the method of claim 68 or 69, the molar ratio of the feed materials among magnesium phosphate pentahydrate, phosphoric acid and MOH is 1:1.5-9:3-18. The method according to any one of claims 68-70, wherein the molar ratio of the feed materials among magnesium phosphate pentahydrate, phosphoric acid and MOH is 1:3:9, 1:9:18, 1:2:5, 1:1.5:3 or 1:6:

21. The method according to any one of claims 68-71, wherein the stirring lasts for at least 3 minutes. The method according to any one of claims 68-72, wherein the stirring lasts for 5-30 minutes. The method according to any one of claims 68-73, wherein the MOH is LiOH, NaOH, KOH, NH4OH or any combination thereof. The method according to any one of claims 68-74, wherein the MOH is LiOH, NaOH, or any combination thereof. The method according to any one of claims 68-75, wherein the MOH is NaOH, KOH, or any combination thereof. The method according to any one of claims 68-76, wherein the MOH is NaOH. The method according to any one of claims 68-77, wherein the MOH is KOH. The method according to any one of claims 68-78, wherein the static aging process lasts for at least 1 minute. According to any one of claims 68-79, the static aging process lasts for at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 1.5 hours, or at least 2 hours. The method according to any one of claims 68-80, wherein the crude product is washed with water as follows: the crude product is mixed with water until homogeneous, centrifuged, the supernatant is removed, and optionally the above washing steps are repeated once or more. The method according to any one of claims 68-81, wherein the volume / volume ratio of the crude product to water is from 1 mL of the crude product to 2 mL of water to 1 mL of the crude product to 32 mL of water. The method according to any one of claims 68-82, wherein the washing steps 2, 3, 4, 5, 6, 7, 8, 9 or 10 are repeated. The method according to any one of claims 68-83, wherein the method further comprises drying the compound of formula I to obtain the compound of formula I in a dried state. A pharmaceutical composition comprising a compound of formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients. A pharmaceutical composition comprising a compound of formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4). The pharmaceutical composition according to claim 86, wherein the active ingredient of the pharmaceutical composition comprises a compound of formula I. The pharmaceutical composition according to claim 86 or 87, wherein the subject is a mammal. The pharmaceutical composition according to any one of claims 86-88, wherein the mammal is a human. The pharmaceutical composition according to any one of claims 86-89, wherein the digestive tract is the intestine. The pharmaceutical composition according to any one of claims 86-90, wherein the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 40 μmol / L, about 45 μmol / L, about 50 μmol / L, about 55 μmol / L, about 60 μmol / L, about 65 μmol / L, about 70 μmol / L, about 75 μmol / L, about 80 μmol / L, about 85 μmol / L, about 90 μmol / L, about 95 μmol / L, about 100 μmol / L, about 150 μmol / L, or about 200 μmol / L before the pharmaceutical composition is administered to the subject. The pharmaceutical composition according to any one of claims 86-91, wherein the level of ammonia and / or ammonium ions in the blood of the subject prior to administration of the pharmaceutical composition is about 200 μmol / L to about 1600 μmol / L, about 300 μmol / L to about 1500 μmol / L, about 400 μmol / L to about 1400 μmol / L, about 500 μmol / L to about 1300 μmol / L, or about 600 μmol / L to about 1200 μmol / L. The pharmaceutical composition according to any one of claims 86-92, wherein after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition for at least a certain period of time. The pharmaceutical composition according to any one of claims 86-93, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The pharmaceutical composition according to any one of claims 86-94, wherein after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1600 μmol / L, ≤ about 1500 μmol / L, ≤ about 1400 μmol / L, ≤ about 1300 μmol / L, ≤ about 1200 μmol / L, ≤ about 1100 μmol / L, ≤ about 1000 μmol / L, ≤ about 900 μmol / L, ≤ about 800 μmol / L, ≤ about 700 μmol / L, ≤ about 600 μmol / L, for at least a certain period of time. l / L, ≤ about 500 μmol / L, ≤ about 400 μmol / L, ≤ about 300 μmol / L, ≤ about 200 μmol / L, ≤ about 100 μmol / L, ≤ about 95 μmol / L, ≤ about 90 μmol / L, ≤ about 85 μmol / L, ≤ about 80 μmol / L, ≤ about 75 μmol / L, ≤ about 70 μmol / L, ≤ about 65 μmol / L, ≤ about 60 μmol / L, ≤ about 55 μmol / L, ≤ about 50 μmol / L, ≤ about 45 μmol / L or ≤ about 40 μmol / L and ≥ about 5 μmol / L. The pharmaceutical composition according to any one of claims 86-95, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The pharmaceutical composition according to any one of claims 86-96, wherein the disease or condition associated with elevated levels of ammonia and / or ammonium ions in the subject's blood and / or digestive tract is hyperammonemia or a disease or condition associated with hyperammonemia. The pharmaceutical composition according to any one of claims 86-97, wherein the hyperammonemia is caused by one or more of the following factors: glutamine synthase deficiency; valproic acid therapy; asparaginase therapy; total parenteral nutrition; cystoscopy with a glycine-containing solution; lung or bone marrow transplantation; portosystemic shunt; ureteral dilatation; multiple myeloma; chemotherapy; infection, such as urinary tract infection; neurogenic bladder; and intestinal bacterial overgrowth. The pharmaceutical composition according to any one of claims 86-98, wherein the disease or condition associated with hyperammonemia is a urea cycle disorder. The pharmaceutical composition according to any one of claims 86-99, wherein the urea cycle disorder is selected from one or more of citrullinemia, argininosuccinateuria, arginase deficiency, N-acetylglutamate synthase deficiency, carbamoyl phosphate synthase deficiency, and ornithine transcarbamoylase deficiency. The pharmaceutical composition according to any one of claims 86-100, wherein the disease or condition associated with hyperammonemia is a liver disease. The pharmaceutical composition according to any one of claims 86-101, wherein the liver disease is selected from one or more of hepatitis, cirrhosis, hepatic encephalopathy, acute liver failure, chronic liver failure, and liver cancer. The pharmaceutical composition according to any one of claims 86-102, wherein the hepatitis is selected from one or more of viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, hepatitis caused by toxic substances, fulminant hepatitis, α1-antitrypsin deficiency, and non-alcoholic steatohepatitis. The pharmaceutical composition according to any one of claims 86-103, wherein the viral hepatitis is selected from one or more of hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, hepatitis F, and hepatitis G. The pharmaceutical composition according to any one of claims 86-104, wherein the disease or condition associated with hyperammonemia is selected from organic acidemia, such as propionic acidemia, isovaleric acidemia, methylmalonic acidemia, or 3-methylcrotonylglycinuria; fatty acid oxidation deficiency; carnitine deficiency; carnitine cycle deficiency; β-oxidation deficiency; lysineuric protein intolerance; pyrroline-5-carboxylic acid synthase deficiency; pyruvate carboxylase deficiency; ornithine aminotransferase deficiency; carbonic anhydrase deficiency; hyperinsulinemia-hyperammonia syndrome; mitochondrial disease; portal hypertension; chronic fatigue syndrome; central nervous system disorders, such as brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, hyperactivity, delusions, hallucinations, hyperactivity, coma, or cognitive impairment; growth retardation; and organ failure, such as respiratory failure, cardiovascular failure, or renal failure, or one or more of these. A pharmaceutical composition comprising a compound of formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is used for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with elevated levels of urea in the blood of a subject; or (5) two or more of (1) to (4). The pharmaceutical composition according to claim 106, wherein the active ingredient of the pharmaceutical composition comprises a compound of formula I. The pharmaceutical composition according to claim 106 or 107, wherein the subject is a mammal. The pharmaceutical composition according to any one of claims 106-108, wherein the mammal is a human. The pharmaceutical composition according to any one of claims 106-109, wherein the digestive tract is the intestine. The pharmaceutical composition according to any one of claims 106-110, wherein the subject's blood urea nitrogen level is higher than about 6 mmol / L, about 6.5 mmol / L, about 7 mmol / L, about 7.5 mmol / L, about 8 mmol / L or about 8.5 mmol / L before the pharmaceutical composition is administered to the subject. The pharmaceutical composition according to any one of claims 106-111, wherein after administration of the pharmaceutical composition to the subject, the level of blood urea nitrogen in the subject is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition for at least a certain period of time. The pharmaceutical composition according to any one of claims 106-112, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The pharmaceutical composition according to any one of claims 106-113, wherein the pharmaceutical composition is used to reduce the urea level in the intestinal contents of the subject. The pharmaceutical composition according to any one of claims 106-114, wherein after administration of the pharmaceutical composition to the subject, the level of urea in the intestinal contents of the subject is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% for at least a certain period of time compared with before administration of the pharmaceutical composition. According to any one of claims 106-115, after administration of the pharmaceutical composition to the subject, the level of urea in the intestinal contents of the subject is ≤ about 100 mg / dL, ≤ about 90 mg / dL, ≤ about 80 mg / dL, ≤ about 70 mg / dL, ≤ about 60 mg / dL, ≤ about 50 mg / dL, ≤ about 40 mg / dL, ≤ about 30 mg / dL, or ≤ about 20 mg / dL for at least a certain period of time. The pharmaceutical composition according to any one of claims 106-116, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The pharmaceutical composition according to any one of claims 106-117, wherein after administration of the pharmaceutical composition to the subject, the pharmaceutical composition maintains an appropriate level of urea or blood urea nitrogen in the subject's blood for at least a certain period of time. According to any one of claims 106-118, the blood urea nitrogen level of the suitable subject is ≥ about 1.5 mmol / L and ≤ about 7.5 mmol / L, ≥ about 2 mmol / L and ≤ about 7 mmol / L, ≥ about 2.5 mmol / L and ≤ about 6.5 mmol / L, or ≥ about 3 mmol / L and ≤ about 6 mmol / L. The pharmaceutical composition according to any one of claims 106-119, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The pharmaceutical composition according to any one of claims 106-120, wherein the disease or condition associated with elevated urea levels in the subject's blood is azotemia. The pharmaceutical composition according to any one of claims 106-121, wherein the azotemia is hyperureemia. The pharmaceutical composition according to any one of claims 106-122, wherein the hyperureemia is caused by excessive urea production or insufficient urea excretion in the subject. The pharmaceutical composition according to any one of claims 106-123, wherein the azotemia is prerenal azotemia, renal azotemia, or postrenal azotemia. The pharmaceutical composition according to any one of claims 106-124, wherein the azotemia is prerenal azotemia. The pharmaceutical composition according to any one of claims 106-125, wherein the prerenal azotemia is caused by one or more of the following factors: hemorrhage, shock, hypovolemia, congestive heart failure, adrenal insufficiency, and renal artery stenosis. The pharmaceutical composition according to any one of claims 106-126, wherein the azotemia is renal azotemia. The pharmaceutical composition according to any one of claims 106-127, wherein the renal azotemia is caused by renal parenchymal damage. The pharmaceutical composition according to any one of claims 106-128, wherein the azotemia is postrenal azotemia. The pharmaceutical composition according to any one of claims 106-129, wherein the postrenal azotemia is caused by one or more of the following factors: vesicoureteral reflux, ureteral obstruction, pregnancy, ureteral compression, benign prostatic hyperplasia, and urethral obstruction. The pharmaceutical composition according to any one of claims 106-130, wherein the disease or condition associated with the elevated urea level in the subject's blood is selected from one or more of the following diseases or conditions: acute renal failure (e.g., acute renal failure caused by one or more of the following factors: acute tubular necrosis, acute nephritis, bacterial infection, and drug poisoning), chronic renal failure (e.g., chronic renal failure caused by one or more of the following factors: chronic glomerulonephritis, diabetes, hypertension, and polycystic kidney disease), uremia, heart failure, myocardial infarction, cardiorenal syndrome, gastrointestinal bleeding, dehydration, fluid loss, diabetes, hyperthyroidism, Cushing's syndrome, bacterial infection, sepsis, drug poisoning, heavy metal poisoning, burns, trauma, malignant tumors, cachexia, side effects of chemotherapy, anorexia, rhabdomyolysis syndrome, chronic liver disease, acute-on-chronic liver disease, and ascites. The medicine box contains: The pharmaceutical composition according to any one of claims 85-131; At least one container for containing the pharmaceutical composition; and Drug instructions and / or drug labels. A method for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) two or more of (1) to (4) above, said method comprising administering to a subject in need a compound of formula I according to any one of claims 1-67 or a pharmaceutical composition comprising a compound of formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients. According to the method of claim 133, the active ingredient of the pharmaceutical composition is composed of a compound of formula I. The method according to claim 133 or 134, wherein the pharmaceutical composition is a unit dosage form. The method according to any one of claims 133-135, wherein the unit dosage form comprises about 0.1 mg to about 200 g of the compound of formula I. The method according to any one of claims 133-136, wherein the unit dosage form comprises about 0.1 mg to about 50 g, for example about 0.5 mg to about 25 g, about 1 mg to about 10 g, about 2 mg to about 5 g, or about 5 mg to about 1 g of a compound of formula I. The method according to any one of claims 133-137, wherein the unit dosage form comprises at least about 0.1 w / w%, such as about 0.1-99.9 w / w%, about 0.2-90 w / w%, about 0.25-80 w / w%, about 0.5-50 w / w%, about 0.75-25 w / w%, or about 1-10 w / w% of a compound of formula I. The method according to any one of claims 133-138, wherein the pharmaceutical composition is formulated for oral administration. The method according to any one of claims 133-139, wherein the pharmaceutical composition is formulated as an oral formulation, optionally in unit dosage form. The method according to any one of claims 133-140, wherein the oral formulation is a solid oral formulation or a liquid oral formulation. The method according to any one of claims 133-141, wherein the solid oral preparation is a powder, granule, tablet, capsule, pill, or lozenge. The method according to any one of claims 133-142, wherein the liquid oral formulation is a suspension. The method according to any one of claims 133-143, wherein the pharmaceutical composition is formulated for administration with or without food. According to any one of claims 133-144, the method of not being administered with meals means that the pharmaceutical composition is administered at an interval of at least 30 min, at least 40 min, at least 50 min, at least 1 h, at least 1.5 h, at least 2 h or longer from food. The method according to any one of claims 133-145, wherein the administration with meals means the pharmaceutical composition is administered simultaneously with food or at intervals of up to 1 min, up to 2 min, up to 3 min, up to 4 min, up to 5 min, up to 10 min, up to 15 min, up to 20 min, or up to 25 min. The method according to any one of claims 133-146, wherein the pharmaceutical composition is formulated for rectal administration. The method according to any one of claims 133-147, wherein the pharmaceutical composition is formulated for administration by enema. The method according to any one of claims 133-148, wherein the pharmaceutical composition is formulated as a rectal preparation, optionally in unit dosage form. The method according to any one of claims 133-149, wherein the rectal administration preparation is a suppository, gel, paste, or enema. The method according to any one of claims 133-150, wherein the pharmaceutical composition is formulated for administration to the subject once, twice, three times, four times or more daily. The method according to any one of claims 133-151, wherein the application lasts for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 10 months, at least 1 year, at least 1.5 years, at least 2 years, at least 2.5 years, at least 3 years, at least 4 years, at least 5 years, at least 10 years, or longer. The method according to any one of claims 133-152, wherein the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg of compound I of formula I / kg / day to about 2000 mg of compound I of formula I / kg / day. According to any one of claims 133-153, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg of compound I / kg / day to about 500 mg of compound I / kg / day, for example, about 10 mg of compound I / kg / day to about 400 mg of compound I / kg / day, about 15 mg of compound I / kg / day to about 300 mg of compound I / kg / day, about 20 mg of compound I / kg / day to about 250 mg of compound I / kg / day, or about 25 mg of compound I / kg / day to about 225 mg of compound I / kg / day. The method according to any one of claims 133-154, wherein the subject is a mammal. The method according to any one of claims 133-155, wherein the mammal is a human. The method according to any one of claims 133-156, wherein the digestive tract is the intestine. The method according to any one of claims 133-157, wherein the level of ammonia and / or ammonium ions in the blood of the subject is higher than about 40 μmol / L, about 45 μmol / L, about 50 μmol / L, about 55 μmol / L, about 60 μmol / L, about 65 μmol / L, about 70 μmol / L, about 75 μmol / L, about 80 μmol / L, about 85 μmol / L, about 90 μmol / L, about 95 μmol / L, about 100 μmol / L, about 150 μmol / L, or about 200 μmol / L before the pharmaceutical composition is administered to the subject. The method according to any one of claims 133-158, wherein the level of ammonia and / or ammonium ions in the blood of the subject before administration of the pharmaceutical composition to the subject is about 200 μmol / L to about 1600 μmol / L, about 300 μmol / L to about 1500 μmol / L, about 400 μmol / L to about 1400 μmol / L, about 500 μmol / L to about 1300 μmol / L, or about 600 μmol / L to about 1200 μmol / L. The method according to any one of claims 133-159, wherein after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% compared to before administration of the pharmaceutical composition for at least a certain period of time. The method according to any one of claims 133-160, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The method according to any one of claims 133-161, wherein after administration of the pharmaceutical composition to the subject, the level of ammonia and / or ammonium ions in the subject's blood is ≤ about 1600 μmol / L, ≤ about 1500 μmol / L, ≤ about 1400 μmol / L, ≤ about 1300 μmol / L, ≤ about 1200 μmol / L, ≤ about 1100 μmol / L, ≤ about 1000 μmol / L, ≤ about 900 μmol / L, ≤ about 800 μmol / L, ≤ about 700 μmol / L, ≤ about 600 μmol / L, for at least a certain period of time. l / L, ≤ about 500 μmol / L, ≤ about 400 μmol / L, ≤ about 300 μmol / L, ≤ about 200 μmol / L, ≤ about 100 μmol / L, ≤ about 95 μmol / L, ≤ about 90 μmol / L, ≤ about 85 μmol / L, ≤ about 80 μmol / L, ≤ about 75 μmol / L, ≤ about 70 μmol / L, ≤ about 65 μmol / L, ≤ about 60 μmol / L, ≤ about 55 μmol / L, ≤ about 50 μmol / L, ≤ about 45 μmol / L or ≤ about 40 μmol / L and ≥ about 5 μmol / L. The method according to any one of claims 133-162, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The method according to any one of claims 133-163, wherein the disease or condition associated with elevated levels of ammonia and / or ammonium ions in the subject's blood and / or digestive tract is hyperammonemia or a disease or condition associated with hyperammonemia. The method according to any one of claims 133-164, wherein the hyperammonemia is caused by one or more of the following factors: glutamine synthase deficiency; valproic acid therapy; asparaginase therapy; total parenteral nutrition; cystoscopy with a glycine-containing solution; lung or bone marrow transplantation; portosystemic shunt; ureteral dilatation; multiple myeloma; chemotherapy; infection, such as urinary tract infection; neurogenic bladder; and intestinal bacterial overgrowth. The method according to any one of claims 133-165, wherein the disease or condition associated with hyperammonemia is a urea cycle disorder. The method according to any one of claims 133-166, wherein the urea cycle disorder is selected from one or more of citrullinemia, argininosuccinateuria, arginase deficiency, N-acetylglutamate synthase deficiency, carbamoyl phosphate synthase deficiency, and ornithine transcarbamoylase deficiency. The method according to any one of claims 133-167, wherein the disease or condition associated with hyperammonemia is a liver disease. The method according to any one of claims 133-168, wherein the liver disease is selected from one or more of hepatitis, cirrhosis, hepatic encephalopathy, acute liver failure, chronic liver failure, and liver cancer. The method according to any one of claims 133-169, wherein the hepatitis is selected from one or more of viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, hepatitis caused by toxic substances, fulminant hepatitis, α1-antitrypsin deficiency, and non-alcoholic steatohepatitis. The method according to any one of claims 133-170, wherein the viral hepatitis is selected from one or more of hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, hepatitis F, and hepatitis G. The method according to any one of claims 133-171, wherein the disease or condition associated with hyperammonemia is selected from organic acidemia, such as propionic acidemia, isovaleric acidemia, methylmalonic acidemia, or 3-methylcrotonylglycinuria; fatty acid oxidation deficiency; carnitine deficiency; carnitine cycle deficiency; β-oxidation deficiency; lysineuric protein intolerance; pyrroline-5-carboxylic acid synthase deficiency; pyruvate carboxylase deficiency; ornithine aminotransferase deficiency; carbonic anhydrase deficiency; hyperinsulinemia-hyperammonia syndrome; mitochondrial disease; portal hypertension; chronic fatigue syndrome; central nervous system disorders, such as brain dysfunction, cerebral edema, slurred speech, tremor, ataxia, seizures, nausea, vomiting, hyperactivity, delusions, hallucinations, hyperactivity, coma, or cognitive impairment; growth retardation; and organ failure, such as respiratory failure, cardiovascular failure, or renal failure, or one or more of these. The use of a compound of Formula I according to any one of claims 1-67 or a pharmaceutical composition comprising a compound of Formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients in the preparation of a medicine for (1) preventing and / or treating a disease or condition associated with elevated levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (2) reducing the levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; (3) absorbing ammonia and / or ammonium ions in the digestive tract of a subject; (4) maintaining appropriate levels of ammonia and / or ammonium ions in the blood and / or digestive tract of a subject; or (5) the use of two or more of the above (1) to (4) in a medicine. A method for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) two or more of (1) to (4) above, the method comprising administering to a subject in need a compound of formula I according to any one of claims 1-67 or a pharmaceutical composition comprising a compound of formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients. According to the method of claim 174, the active ingredient of the pharmaceutical composition is composed of a compound of formula I. The method according to claim 174 or 175, wherein the pharmaceutical composition is a unit dosage form. The method according to any one of claims 174-176, wherein the unit dosage form comprises about 0.1 mg to about 200 g of the compound of formula I. The method according to any one of claims 174-177, wherein the unit dosage form comprises about 0.1 mg to about 50 g, for example about 0.5 mg to about 25 g, about 1 mg to about 10 g, about 2 mg to about 5 g, or about 5 mg to about 1 g of a compound of formula I. The method according to any one of claims 174-178, wherein the unit dosage form comprises at least about 0.1 w / w%, such as about 0.1-99.9 w / w%, about 0.2-90 w / w%, about 0.25-80 w / w%, about 0.5-50 w / w%, about 0.75-25 w / w%, or about 1-10 w / w% of a compound of formula I. The method according to any one of claims 174-179, wherein the pharmaceutical composition is formulated for oral administration. The method according to any one of claims 174-180, wherein the pharmaceutical composition is formulated as an oral formulation, optionally in unit dosage form. The method according to any one of claims 174-181, wherein the oral formulation is a solid oral formulation or a liquid oral formulation. The method according to any one of claims 174-182, wherein the solid oral preparation is a powder, granule, tablet, capsule, pill, or lozenge. The method according to any one of claims 174-183, wherein the liquid oral formulation is a suspension. The method according to any one of claims 174-184, wherein the pharmaceutical composition is formulated for administration with or without food. According to any one of claims 174-185, the method of not being administered with meals means that the pharmaceutical composition is administered at an interval of at least 30 min, at least 40 min, at least 50 min, at least 1 h, at least 1.5 h, at least 2 h, or longer between food and the administration. The method according to any one of claims 174-186, wherein the administration with meals means the administration of the pharmaceutical composition with food at the same time or at intervals of up to 1 min, up to 2 min, up to 3 min, up to 4 min, up to 5 min, up to 10 min, up to 15 min, up to 20 min, or up to 25 min. The method according to any one of claims 174-187, wherein the pharmaceutical composition is formulated for rectal administration. The method according to any one of claims 174-188, wherein the pharmaceutical composition is formulated for administration by enema. The method according to any one of claims 174-189, wherein the pharmaceutical composition is formulated as a rectal preparation, optionally in unit dosage form. The method according to any one of claims 174-190, wherein the rectal administration formulation is a suppository, gel, paste, or enema. The method according to any one of claims 174-191, wherein the pharmaceutical composition is formulated for administration to the subject once, twice, three times, four times or more daily. The method according to any one of claims 174-192, wherein the application lasts for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 10 months, at least 1 year, at least 1.5 years, at least 2 years, at least 2.5 years, at least 3 years, at least 4 years, at least 5 years, at least 10 years, or longer. The method according to any one of claims 174-193, wherein the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg of compound I of formula I / kg / day to about 2000 mg of compound I of formula I / kg / day. According to any one of claims 174-194, the pharmaceutical composition is formulated for administration to the subject at a dose of about 5 mg of compound I / kg / day to about 500 mg of compound I / kg / day, for example, about 10 mg of compound I / kg / day to about 400 mg of compound I / kg / day, about 15 mg of compound I / kg / day to about 300 mg of compound I / kg / day, about 20 mg of compound I / kg / day to about 250 mg of compound I / kg / day, or about 25 mg of compound I / kg / day to about 225 mg of compound I / kg / day. The method according to any one of claims 174-195, wherein the subject is a mammal. The method according to any one of claims 174-196, wherein the mammal is a human. The method according to any one of claims 174-197, wherein the digestive tract is the intestine. The method according to any one of claims 174-198, wherein the subject's blood urea nitrogen level is higher than about 6 mmol / L, about 6.5 mmol / L, about 7 mmol / L, about 7.5 mmol / L, about 8 mmol / L, or about 8.5 mmol / L before the subject is given the pharmaceutical composition. The method according to any one of claims 174-199, wherein after administration of the pharmaceutical composition to the subject, the subject's blood urea nitrogen level is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% for at least a certain period of time compared to before administration of the pharmaceutical composition. The method according to any one of claims 174-200, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The method according to any one of claims 174-201, wherein the pharmaceutical composition is used to reduce the urea level in the intestinal contents of the subject. The method according to any one of claims 174-202, wherein after administration of the pharmaceutical composition to the subject, the level of urea in the intestinal contents of the subject is reduced by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, or about 90% for at least a certain period of time compared to before administration of the pharmaceutical composition. According to any one of claims 174-203, after administration of the pharmaceutical composition to the subject, the urea level in the intestinal contents of the subject is ≤ about 100 mg / dL, ≤ about 90 mg / dL, ≤ about 80 mg / dL, ≤ about 70 mg / dL, ≤ about 60 mg / dL, ≤ about 50 mg / dL, ≤ about 40 mg / dL, ≤ about 30 mg / dL, or ≤ about 20 mg / dL for at least a certain period of time. The method according to any one of claims 174-204, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The method according to any one of claims 174-205, wherein after administration of the pharmaceutical composition to the subject, the pharmaceutical composition maintains an appropriate level of urea or blood urea nitrogen in the subject's blood for at least a certain period of time. According to any one of claims 174-206, the blood urea nitrogen level of the appropriate subject is ≥ about 1.5 mmol / L and ≤ about 7.5 mmol / L, ≥ about 2 mmol / L and ≤ about 7 mmol / L, ≥ about 2.5 mmol / L and ≤ about 6.5 mmol / L, or ≥ about 3 mmol / L and ≤ about 6 mmol / L. The method according to any one of claims 174-207, wherein the time period is at least 0.5 hours, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. The method according to any one of claims 174-208, wherein the disease or condition associated with the elevated urea level in the subject's blood is azotemia. The method according to any one of claims 174-209, wherein the azotemia is hyperureemia. The method according to any one of claims 174-210, wherein the hyperureemia is caused by excessive urea production or insufficient urea excretion in the subject. The method according to any one of claims 174-211, wherein the azotemia is prerenal azotemia, renal azotemia, or postrenal azotemia. The method according to any one of claims 174-212, wherein the azotemia is prerenal azotemia. The method according to any one of claims 174-213, wherein the prerenal azotemia is caused by one or more of the following factors: hemorrhage, shock, hypovolemia, congestive heart failure, adrenal insufficiency, and renal artery stenosis. The method according to any one of claims 174-214, wherein the azotemia is renal azotemia. The method according to any one of claims 174-215, wherein the renal azotemia is caused by renal parenchymal damage. The method according to any one of claims 174-216, wherein the azotemia is postrenal azotemia. The method according to any one of claims 174-217, wherein the postrenal azotemia is caused by one or more of the following factors: vesicoureteral reflux, ureteral obstruction, pregnancy, ureteral compression, benign prostatic hyperplasia, and urethral obstruction. The method according to any one of claims 174-218, wherein the disease or condition associated with the elevated urea level in the subject's blood is selected from one or more of the following diseases or conditions: acute renal failure (e.g., acute renal failure caused by one or more of the following factors: acute tubular necrosis, acute nephritis, bacterial infection, and drug poisoning), chronic renal failure (e.g., chronic renal failure caused by one or more of the following factors: chronic glomerulonephritis, diabetes, hypertension, and polycystic kidney disease), uremia, heart failure, myocardial infarction, cardiorenal syndrome, gastrointestinal bleeding, dehydration, fluid loss, diabetes, hyperthyroidism, Cushing's syndrome, bacterial infection, sepsis, drug poisoning, heavy metal poisoning, burns, trauma, malignant tumors, cachexia, side effects of chemotherapy, anorexia, rhabdomyolysis syndrome, chronic liver disease, acute-on-chronic liver disease, and ascites. The use of a compound of Formula I according to any one of claims 1-67 or a pharmaceutical composition comprising a compound of Formula I according to any one of claims 1-67 and optionally one or more pharmaceutically acceptable excipients in the preparation of a drug for (1) reducing the level of urea or blood urea nitrogen (BUN) in the blood of a subject; (2) reducing the level of urea in the gastrointestinal contents of a subject; (3) maintaining an appropriate level of urea or blood urea nitrogen in the blood of a subject; (4) preventing and / or treating a disease or condition associated with an elevated level of urea in the blood of a subject; or (5) the use of two or more of the above (1) to (4) in a pharmaceutical preparation.

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