Systemic preparations of pyridinone derivatives for celiac disease

Abstract

The present invention provides systemic formulations, particularly oral formulations, for use in the prevention and / or treatment of celiac disease. [Solution] A systemic formulation is provided comprising a compound of formula I, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, wherein the systemic formulation comprises at least one acidifying agent. TIFF2026086651000024.tif47170

Description

Detailed description of the invention

[0001] The present invention relates to a systemic formulation, particularly an oral formulation, for the prevention and / or treatment of celiac disease, i.e., for use in the prevention and / or treatment of celiac disease.

[0002] [Background of the Invention] Celiac disease is a gluten intolerance and a highly prevalent medical condition. It is characterized by chronic inflammation of the mucosa of the small intestine. In affected patients, the small intestinal epithelium is progressively destroyed after the ingestion of gluten-containing foods, resulting in reduced nutrient absorption. This has a significant impact on affected patients, leading to symptoms such as weight loss, anemia, diarrhea, nausea, loss of appetite, and fatigue. These findings highlight a great need for the development of pharmaceuticals for the treatment of celiac disease and other diseases associated with tissue transglutaminase. Tissue transglutaminase is a central component in the pathogenesis of celiac disease. This endogenous enzyme catalyzes the deamidation of gluten / gliadin in the small intestinal mucosa, thus greatly increasing the inflammatory response. Therefore, inhibitors of tissue transglutaminase are suitable for use as activators against celiac disease. Although several compounds are available that may be suitable for the treatment of celiac disease, some drawbacks are associated with these compounds, particularly their selectivity. Furthermore, especially in the case of systemic therapy, establishing the appropriate bioavailability of drugs under physiological conditions remains a major challenge in the pharmaceutical field. Moreover, in the case of celiac disease, local availability in the duodenum and high drug levels in duodenal tissue must be achieved.

[0003] The object of the present invention is to provide a pharmaceutical formulation that exhibits local applicability, bioavailability, and in vivo inhibitory effects, and is particularly useful for the prevention and / or treatment of celiac disease.

[0004] The object of the present invention is resolved by teaching the independent claims. Further advantageous features, embodiments, and details of the present invention are evident from the dependent claims, specification, drawings, and examples of this application.

[0005] [Brief Description of the Invention] The object of the present invention is to provide for use in the prevention and / or treatment of celiac disease the formula (I) (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate

[0006] [ka] , or including enantiomers, solvates, hydrates, or pharmaceutically acceptable salts of formula (I). This is resolved by a formulation, preferably a systemic formulation.

[0007] Unexpectedly, we were able to demonstrate that the compound according to formula (I) exhibits both local availability in the duodenum and systemic availability (bioavailability) in duodenal tissue when administered orally.

[0008] Pharmacokinetic studies demonstrated bioavailability after oral administration in various species, and bioavailability was significantly increased in humans with the application of systemic formulations (Examples 3 and 4).

[0009] [Description of the invention] The term “systemic formulation” refers to a pharmaceutical composition suitable for administering a drug or active agent so that it is systemically available throughout the entire body of an organism, such as a type of circulatory system drug, and thus affecting the whole body. Administration can be done via intestinal administration (absorption of the drug through the gastrointestinal tract) or parenteral administration (e.g., lung, nasal, injection, or infusion). Preferably, the term “systemic formulation” excludes formulations for intravenous administration. The circulatory system, also called the cardiovascular system or vascular system, is the organ system that allows blood to circulate and transport nutrients (e.g., amino acids and electrolytes), oxygen, carbon dioxide, hormones, and blood cells to and from cells in the body in order to provide nourishment, as well as helping to fight disease, stabilize temperature and pH, and maintain homeostasis.

[0010] The circulatory system includes the lymphatic system, which circulates lymphatic fluid. For example, the passage of lymphatic fluid takes much longer than the passage of blood. Therefore, the term “systemic preparation” refers to a preparation in which the drug is distributed throughout the body of the organism, for example, by the circulatory system or the lymphatic system throughout the body, for example, after intravenous or intramuscular injection, or after ingestion of a tablet, i.e., after enteral administration, especially after oral or parenteral administration.

[0011] The systemic formulations disclosed herein are preferably in the form of tablets, coated tablets, capsules, powders, or granules. In contrast, a "topical formulation" is a formulation that is applied to a specific location on or within the body where the topical formulation is intended to act. Topical means "place", "locally", "at a specific site", "externally", or "limited to a specific part of the body". Thus, it can reduce the risk of undesirable side effects that may occur in other parts of the organism. In most cases, topical administration means application to the body surface, such as the skin or mucosa, to treat diseases by a wide variety of types including creams, foams, gels, lotions, and ointments. Many topical drugs are transdermal, meaning they are applied directly to the skin. Topical drugs may also be applied to the surface of tissues other than the skin, such as inhaled drugs like asthma medications, or eye drops applied to the conjunctiva, or ear drops placed in the ear, drugs applied to the surface of the teeth, or drug application using a pump such as an osmotic pump.

[0012] Topical formulations include, but are not limited to, ear, buccal, intratracheal, transdermal, inhaled, intra-articular, intramuscular gluteal, intracardiac, intradermal, intralumbar, intralymphatic, intramammary, intranasal, intraneural, intraocular, intraorbital, intraosseous, intracardiac, intrathoracic, intramedullary, intratracheal, intraurethral, intrauterine, intraventricular, intravesical, intravitreal, conjunctiva, skin, nose, perineural, retrobulbar, subconjunctival, vagina, and cilia.

[0013] As used herein, the term "parenteral formulation" generally refers to formulations administered by injection or infusion, including, but not limited to, epidural, intra-arterial, intravenous, intrathecal, intravascular, intramuscular, intraperitoneal, intrathoracic, subcutaneous, subepidermal, and transdermal injections and infusions. Preferably, parenteral formulations include epidural, intrathecal, intravascular, intramuscular, intraperitoneal, intrathoracic, subcutaneous, subepidermal, and transdermal injections and infusions, or are selected from the group consisting of... Preferably, intra-arterial and intravenous formulations are excluded from parenteral formulations.

[0014] As used herein, "enteral preparation" generally refers to a preparation of a drug that is absorbed through the mouth (per os, orally, perorally): tablets, dragees, capsules, juices, drops, etc. These drugs are absorbed into the blood of the digestive tract and then enter the liver via the portal vein system and then enter the bloodstream via the hepatic vein. The terms used herein refer to commonly administered preparations including, but not limited to, enteral, intraluminal of the digestive tract, sublingual, peroral (oral), and rectal administration. Preferably, the enteral preparation consists of a preparation selected from the group consisting of or comprising enteral, intraluminal of the digestive tract, sublingual, peroral (oral), and rectal.

[0015] As used herein, "oral preparation" generally refers to a preparation of a drug that is absorbed through the mouth (orally, perorally): tablets, dragees, capsules, juices, drops, etc. These drugs are absorbed into the blood of the digestive tract and then enter the liver via the portal vein system and then enter the bloodstream via the hepatic vein. The terms used herein refer to preparations administered orally.

[0016] Systemic formulations may be in liquid or solid form, including solutions, oral drops, suspensions, emulsions, powders, granules such as effervescent granules, tablets such as uncoated tablets, coated tablets, effervescent tablets, soluble tablets, chewable tablets, oral lyophilized products, lozenges, pastilles, compressed lozenges, sublingual tablets, buccal tablets, granules, effervescent granules, and capsules, powders, granules, microgranules, and pellets. In particular, systemic formulations can be liquid formulations including oral solutions, suspensions, emulsions, powders and granules for oral solutions and suspensions, oral drops, powders for oral drops, syrups, and powders and granules for syrups, or solid forms including uncoated tablets, coated tablets, effervescent tablets, soluble tablets, chewable tablets, oral lyophilized products, lozenges, pastilles, compressed lozenges, sublingual tablets, buccal tablets, granules, effervescent granules and capsules. Uncoated tablets and coated tablets, and capsules, are preferred pharmaceutical formulations whether hard or soft. Most preferably, the formulation is a tablet or a capsule. Examples may include water or a water / propylene glycol solution for parenteral injection, or the addition of sweeteners and opacifiers for oral solutions, oral suspensions, and oral emulsions. Preferably, the systemic formulation is a solid formulation, more preferably a solid enteral formulation, and most preferably an oral formulation or a solid oral formulation.

[0017] As used herein, "topical administration" refers to the administration of a topical preparation. As used herein, "systemic administration" refers to the administration of a systemic preparation. As used herein, “topical availability” refers to the release of the drug from the formulation to a site where it is to be absorbed by a specific tissue or organ, such as from the vehicle or tablet of the formulation, and therefore the drug can act in all locations.

[0018] As used herein, "systemic availability" refers to the proportion of a drug dose that reaches the systemic circulation intact after administration via routes other than intravenous. The term "systemic availability" also refers to the extent to which a drug or other substance is taken up by specific tissues or organs after administration. For example, a drug administered orally and that overcomes the intestinal epithelial barrier is systemically available, or in other words, systemically available, because it is present in the intestinal tissue. "Systemic availability" and "systemically available" are synonymous with "bioavailability" or "bioavailable." Therefore, locally administered compounds also exhibit systemic availability, which is particularly important when the drug target is located beyond the epithelial barrier, as in celiac disease.

[0019] The term "drug level" refers to the level of a drug in plasma, tissue, or organ, while the phrase "systemic availability at target site" refers to the same aspect. As used herein, the term "pharmaceutically acceptable salt" refers to a salt of a particular component that has the same activity as the unmodified compound and is not biologically or otherwise undesirable.

[0020] Pharmacologically acceptable salts can be formed, for example, with organic or inorganic acids. Suitable acids include acetic acid, acetylsalicylic acid, organic dicarboxylic acids, such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, etc., organic tricarboxylic acids, such as citric acid, or sodium bicarbonate, alginic acid, ascorbic acid, aspartic acid, benzoic acid, benzenesulfonic acid, bisulfate, boric acid, butyric acid, camphoric acid, camphorsulfonic acid, carbonic acid, citric acid, cyclopentanepropionic acid, digluconate, dodecyl sulfate, ethanesulfonic acid, formic acid, fumaric acid, glyceric acid, glycerophosphate, glycine, and glycine. The acid is derived from natural and synthetic sources and includes lucoheptanoic acid, gluconic acid, glutamic acid, glutaric acid, glycolic acid, hemisulfate, heptanoic acid, hexanoic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucoic acid, naphthylenesulfonic acid, naphthic acid, nicotinic acid, nitrite, oxalic acid, pelargonic acid, phosphoric acid, propionic acid, saccharin, salicylic acid, sorbic acid, succinic acid, sulfuric acid, tartaric acid, thiocyanic acid, thioglycolic acid, thiosulfate, tosylic acid, undecylenic acid, and amino acids of natural and synthetic origin. Preferably, the acid is adipic acid, fumaric acid, or glutaric acid, and more preferably, the acid is adipic acid.

[0021] Therefore, further aspects of the present invention are for use in the prevention and / or treatment of celiac disease, Equation (I):

[0022] [ka] The subject is the salt of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, or hydrate.

[0023] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease, formula (I):

[0024] [ka] The present invention relates to a systemic formulation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate and a salt of adipic acid, or an enantiomer, solvate, or hydrate of formula (I) and a salt of adipic acid.

[0025] As used herein, the term “solvate” refers to compounds that form complexes through coordination with solvent molecules, particularly these forms of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate.

[0026] As used herein, the term “hydrate” refers to compounds that form complexes through coordination with water molecules, in particular these forms of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate.

[0027] In this specification, the terms “effective dose” or “therapeutic dose” in reference to an activator, or pharmaceutically active agent or drug, or active pharmaceutical ingredient, are synonymous and refer to the amount of an activator, or pharmaceutically active agent or drug, or active pharmaceutical ingredient sufficient to produce the desired pharmacological effect. Therefore, these amounts are effective in treating a disease but low enough to avoid serious side effects. A therapeutic dose of a pharmaceutically active agent, when applied repeatedly over time, will result in substantial relief of the condition. The effective dose of a pharmaceutically active agent varies depending on the specific condition being treated, the severity of the condition, the duration of treatment, the specific components of the composition used, and similar factors.

[0028] As used herein, the terms “activator,” “pharmaceutically active agent,” “drug,” or “active pharmaceutical ingredient” are used synonymously herein and refer to compounds that exhibit therapeutic effects on mammals, particularly humans.

[0029] As used herein, the term "pharmaceutical composition" refers to a composition that, when administered, exhibits a therapeutic effect on mammals. The systemic formulations for use in the prevention and / or treatment of celiac disease according to the present invention as described herein preferably comprise (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate.

[0030] Therefore, embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. Equation (I):

[0031] [ka] The subject is a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate.

[0032] Furthermore, the systemic formulation may be an enteral formulation or a parenteral formulation. Embodiments of the present invention thus relate to a systemic formulation for use in the prevention and / or treatment of celiac disease comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, wherein the systemic formulation is in the form of an enteral formulation or a parenteral formulation.

[0033] Systemic formulations are preferably in the form of oral formulations, particularly oral solid formulations. Oral formulations are a specific form in enteral formulations. Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, where the systemic formulation is in the form of an oral formulation.

[0034] Furthermore, (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate can be administered in the form of its pharmaceutically active salt, solvate, or hydrate, optionally with an essentially non-toxic, pharmaceutically acceptable carrier, matrix, excipient, or expander. Formulations are prepared in known manner on conventional solid or fluid carriers using appropriate doses of conventional pharmaceutically acceptable excipients.

[0035] Therefore, the systemic formulation according to the present invention may further contain excipients. Accordingly, embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethylamino) for use in the prevention and / or treatment of celiac disease. The subject is a systemic formulation comprising or consisting of (1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient.

[0036] For drug delivery targeting the duodenum, i.e., specifically to the duodenum, a formulation exhibiting rapid release after gastric passage is required. Subsequently, the administered drug dose must dissolve rapidly and completely. pH fluctuations in the stomach after oral administration must be compensated for, and efficient dissolution of the administered drug dose must be ensured. A higher systemic availability (AUC), combined with mucosal uptake in the duodenum (indicated by initial tmax), is expected to lead to a higher pharmacological effect.

[0037] Release in the duodenum is indicated by the initial tmax, where tmax is the time at which the maximum concentration in plasma, tissue, or organ can be measured. Excipients can be acidifying agents. The term "acidifying agent" refers to a substance that, when dissolved in water, produces a pH level of less than 7.0. Therefore, the systemic formulation according to the present invention may contain an acidifying agent. Acidifying agents include organic acids, such as ascorbic acid; organic dicarboxylic acids, such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid (hexanediic acid), or glutamic acid; and organic tricarboxylic acids, such as citric acid or sodium hydrogen citrate. Preferably, the acidifying agent is adipic acid.

[0038] With respect to systemic formulations disclosed herein, preferred "acidifying agents" are selected from the group consisting of ascorbic acid, organic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, glutamic acid, etc., and organic tricarboxylic acids such as citric acid and sodium hydrogen citrate.

[0039] More preferred "acidifying agents" with respect to the systemic formulations disclosed herein are selected from the group consisting of adipic acid, fumaric acid, and glutaric acid. Therefore, the systemic formulation according to the present invention may contain an acidifying agent.

[0040] Preferred embodiments of the present invention relate to systemic formulations comprising or for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is an acidifying agent.

[0041] Another preferred embodiment of the present invention is for use in the prevention and / or treatment of celiac disease, Equation (I)

[0042] [ka] The present invention relates to a systemic formulation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer thereof, solvate, hydrate, or pharmaceutically acceptable salt thereof, and at least one acidifying agent.

[0043] Preferred embodiments of the present invention relate to systemic formulations comprising or for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is an acidifying agent, wherein at least one acidifying agent is selected from the group comprising or comprising organic dicarboxylic acids and organic tricarboxylic acids. Preferably, at least one acidifying agent is selected from the group comprising or comprising organic dicarboxylic acids and organic tricarboxylic acids. More preferably, at least one acidifying agent is selected from the group consisting of organic dicarboxylic acids and organic tricarboxylic acids.

[0044] Accordingly, preferred embodiments of the present invention relate to systemic formulations comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one acidifying agent, wherein the at least one acidifying agent is selected from the group comprising or comprising organic dicarboxylic acids and organic tricarboxylic acids.

[0045] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable substance, preferably for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a salt and at least one excipient, wherein the at least one excipient is an acidifying agent, and wherein the at least one acidifying agent includes ascorbic acid, organic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, glutamic acid, etc., and organic tricarboxylic acids, citric acid, and sodium hydrogen citrate, etc. The acidifying agent is selected from the group consisting of or . Preferably, at least one acidifying agent is selected from the group consisting of ascorbic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, glutamic acid, citric acid, and sodium hydrogen citrate. More preferably, at least one acidifying agent is selected from the group consisting of or including oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid (hexanedioic acid), or glutamic acid.

[0046] Preferred embodiments of the present invention relate to a systemic formulation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one acidifying agent, wherein the at least one acidifying agent is selected from the group comprising or consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid (hexanediic acid), or glutamic acid.

[0047] Preferred embodiments of the present invention relate to systemic formulations comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one acidifying agent, wherein the at least one acidifying agent is selected from the group comprising adipic acid (hexanediic acid), fumaric acid, and glutaric acid.

[0048] A particularly preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and at least one excipient, wherein the at least one excipient is an acidifying agent, wherein the acidifying agent is adipic acid.

[0049] Particularly preferred embodiments of the present invention relate to a systemic formulation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one acidifying agent, wherein the at least one acidifying agent is adipic acid.

[0050] Particularly preferred embodiments of the present invention relate to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and adipic acid.

[0051] The drug solution, after passing through the stomach, is transported to the duodenum, which is the site of action. This passage is associated with an increase in pH from approximately 2 to approximately 6, at least in a fasted state. The amount of the substance must remain in the solution; that is, the drug should not precipitate. This effect can be achieved by adding a polymer precipitation inhibitor. Therefore, polymer precipitation inhibitors inhibit the crystallization of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and function as crystallization inhibitors.

[0052] Polymer precipitation inhibitors are polymers capable of stabilizing the supersaturation phase of a drug; that is, polymer precipitation inhibitors can prevent nucleation of drug molecules or the growth of initially formed drug particles, which is achieved by preventing particle-particle interactions by coating the surface of the drug particles or by increasing the viscosity of the suspension medium. The ability of precipitation inhibitors to kinetically stabilize the supersaturation state of a drug is thought to be due to intermolecular interactions between the drug and the polymer in solution (e.g., via hydrogen bonding or hydrophobic interactions), the polymer's ability to sterically interfere with the crystallization process, or an increase in the viscosity of the suspension medium.

[0053] The saturated solubility of the compound is low at the pH value of the duodenum (Example 5 and Figure 4). However, the compound is soluble in the acidic environment of the stomach, supported by the addition of an acidifying agent that results in a supersaturated solution before entering the small intestine. This solution is stabilized by the addition of a polymer precipitation inhibitor, which can also act as a binder. Upon reaching the duodenum, the solubility of the compound decreases as the pH value of the solution increases. However, in this aqueous solution, the polymer precipitation inhibitor and / or binder exert their effects by slowing the precipitation or crystallization of the drug through complex formation. Separately, the binder / polymer precipitation inhibitor increases the viscosity in the medium, which further enhances the effect.

[0054] Therefore, the systemic formulation according to the present invention may further include a polymer precipitation inhibitor. Thus, the excipient may be a polymer precipitation inhibitor. The term "polymer precipitation inhibitor" refers to a substance that slows down the precipitation or crystallization of a drug.

[0055] "Polymer precipitation inhibitors" include cellulose derivatives, starch derivatives, dextran / dextrin derivatives, polyether derivatives, polyvinyl derivatives, polyacrylic acid derivatives, and polyamine derivatives, polysulfonic acid derivatives, and combinations thereof.

[0056] In some embodiments, the "polymer precipitation inhibitor" is This includes, but is not limited to, microcrystalline cellulose (MCC), cellulose acetate phthalate (CAP), cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate butyrate (CAB), cellulose acetate trimellitate (CAT), methylcellulose (MC), methylcellulose acetate phthalate, ethylcellulose (EC), carboxymethylcellulose (CMC), sodium carboxymethylcellulose, carboxymethylethylcellulose (CMEC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC or hypromellose), L-hydroxypropylcellulose, hydroxypropyl methylcellulose (HPMC or hypromellose), carboxymethyl hydroxyethylcellulose (CMHEC), sodium carboxymethyl hydroxyethylcellulose (NaCMHEC), hydroxypropyl methylcellulose phthalate (HPMCP, hypromellose phthalate), and hydroxypropyl methylcellulose acetate succinate (HPMCAS, hypromellose acetate succinate), as well as other cellulose derivatives. Hydroxyethyl starch, hydroxypropyl starch (HPS), and alpha Starch derivatives, including but not limited to these, Dextran / dextrin derivatives include, but are not limited to, cyclodextran (i.e., cycloisomalto-heptaose (CI-7), cycloisomalto-octaose (CI-8), cycloisomalto-nonaose (CI-9)), hydroxypropyl dextran, maltodextrin, α- / β- / γ-cyclodextrin, 2-hydroxyethyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether-β-cyclodextrin sodium salt, methylated-β-cyclodextrin, and 2-hydroxypropyl-γ-cyclodextrin. Polyether derivatives include, but are not limited to, polyethylene glycol (PEG), polyethylene oxide (PEO), polyether polyols, poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, poloxamer), such as poloxamer 188 and poloxamer 407. Polyvinyl derivatives include, but are not limited to, polyvinyl alcohol (PVA), polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-co(co)-polyvinyl acetate (PVPVA), and polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®). Polyacrylic acid derivatives include, but are not limited to, poly(acrylic acid) (PAA), poly(acrylamide / acrylic acid) (PAC-AC), polymethyl acrylate (PMA), polymethacrylic acid, poly(methacrylic acid / methyl methacrylate), and poly(methacrylic acid / ethyl acrylate). Polyamine derivatives include, but are not limited to, polyethyleneimine (PEI), polyallylamine hydrogen chloride, polydiallyldimethylammonium chloride, and poly(2-ethyl-2-oxazoline). Polystyrene sulfonic acid (PSSA), and polysulfonic acid derivatives, and A combination of at least two of the above polymer precipitation inhibitors, Selected from the group that includes or consists of.

[0057] Preferably, the "polymer precipitation inhibitor" is microcrystalline cellulose (MCC), cellulose acetate phthalate (CAP), cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate butyrate (CAB), cellulose acetate trimellitate (CAT), methylcellulose (MC), methylcellulose acetate phthalate, ethylcellulose (EC), carboxymethylcellulose (CMC), sodium carboxymethylcellulose, carboxymethylethylcellulose (CMEC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC or hypromellose), L-hydroxypropylcellulose, hydroxypropylmethylcellulose (HPMC or hypromellose), or carboxymethylhydroxyethylcellulose. Sodium hydroxyethylcellulose (CMHEC), sodium carboxymethyl hydroxyethylcellulose (NaCMHEC), hydroxypropyl methylcellulose phthalate (HPMCP, hypromellose phthalate), hydroxypropyl methylcellulose acetate succinate (HPMCAS, hypromellose acetate succinate), hydroxyethyl starch, hydroxypropyl starch (HPS), and pregelatinized starch, cyclodextran (i.e., cycloisomalto-heptaose (CI-7), cycloisomalto-octaose (CI-8), cycloisomalto-nonaose (CI-9)), hydroxypropyl dextran, maltodextrin, α- / β- / γ-cyclodextrin, 2-hydroxyethyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether-β -Cyclodextrin sodium salt, methylated-β-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin, polyethylene glycol (PEG), polyethylene oxide (PEO), polyether polyol, poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, poloxamer), e.g., poloxamer 188 and poloxamer 407, polyvinyl alcohol (PVA), polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone (PVP), polyvinylpyrrolidone Lydon-co(co)-polyvinyl acetate (PVPVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), poly(acrylic acid) (PAA), poly(acrylamide / acrylic acid) (PAC-AC), polymethyl acrylate (PMA), polymethacrylic acid, poly(methacrylic acid / methyl methacrylate), poly(methacrylic acid / ethyl acrylate), polyethyleneimine (PEI), polyallylamine hydrogen chloride, polydiallyldimethylammonium chloride, poly(2-ethyl-2-oxazoline), polystyrene sulfonic acid (PSSA), and A combination of at least two of the above polymer precipitation inhibitors, Selected from the group that includes or consists of.

[0058] More preferably, the "polymer precipitation inhibitor" is microcrystalline cellulose (MCC), cellulose acetate phthalate (CAP), cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate butyrate (CAB), cellulose acetate trimellitate (CAT), methylcellulose (MC), methylcellulose acetate phthalate, ethylcellulose (EC), carboxymethylcellulose (CMC), sodium carboxymethylcellulose, carboxymethylethylcellulose (CMEC), hydroxymethylcellulose (HMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC or hypromellose), L-hydroxypropylcellulose, hydroxypropylmethylcellulose (HPMC or hypromellose), carboxymethylhydroxyethylcellulose (CMHEC), sodium carboxymethylhydroxyethylcellulose (NaCMHEC), hydroxypropylmethylcellulose phthalate (HPMCP, hypromellose phthalate), hydroxypropylmethylcellulose Hypromellose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyethylene oxide (PEO), polyether polyol, poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, poloxamer), e.g., poloxamer 188 and poloxamer 407, polyvinyl alcohol (PVA), polyvinyl acetate Phthalates (PVAP), polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-co(co)-polyvinyl acetate (PVPVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), poly(acrylic acid) (PAA), poly(acrylamide / acrylic acid) (PAC-AC), polymethyl acrylate (PMA), polymethacrylic acid, poly(methacrylic acid / methyl methacrylate), poly(methacrylic acid / ethyl acrylate), and A combination of at least two of the above polymer precipitation inhibitors, Selected from the group that includes or consists of.

[0059] More preferably, suitable polymer precipitation inhibitors include L-hydroxypropylcellulose, hydroxypropylmethylcellulose, a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, polyethylene glycol (PEG), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (=poloxama The polymer precipitation inhibitor comprises polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), carboxymethylcellulose (CMC), methylcellulose (MC), hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), and / or sodium carboxymethylcellulose. More preferably, the polymer precipitation inhibitor is selected from the group comprising or consisting of polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, and cellulose derivatives. More preferably, the polymer precipitation inhibitor is polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, cellulose derivatives, or a combination of cellulose and cellulose derivatives.

[0060] Preferably, cellulose is microcrystalline cellulose (MCC), and cellulose derivatives include microcrystalline cellulose (MCC), cellulose acetate phthalate (CAP), cellulose acetate terephthalate, cellulose acetate isophthalate, cellulose acetate butyrate (CAB), cellulose acetate trimellitate (CAT), methylcellulose (MC), methylcellulose acetate phthalate, ethylcellulose (EC), carboxymethylcellulose (CMC), carboxymethylcellulose sodium, carboxymethylethylcellulose (CMEC), and hydroxymethylcellulose. The following are selected from the group consisting of HMC, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC or hypromellose), L-hydroxypropylcellulose, hydroxypropylmethylcellulose (HPMC or hypromellose), carboxymethylhydroxyethylcellulose (CMHEC), sodium carboxymethylhydroxyethylcellulose (NaCMHEC), hydroxymethylcellulose phthalate (HPMCP, hypromellose phthalate), and hydroxypropylmethylcellulose acetate succinate (HPMCAS, hypromellose acetate succinate).

[0061] More preferably, the polymer precipitation inhibitor is selected from the group comprising or consisting of polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropyl cellulose, and hydroxypropyl cellulose. Most preferably, the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropyl cellulose, hydroxypropyl cellulose, or a combination of L-hydroxypropyl cellulose and hydroxypropyl cellulose. The combination of L-hydroxypropyl cellulose and hydroxypropyl cellulose acts as both a polymer precipitation inhibitor and a disintegrant, and therefore can reduce the amount of disintegrant.

[0062] The systemic formulations disclosed herein, and in particular systemic formulations for oral administration, most preferably include, as polymer precipitation inhibitors, polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose.

[0063] The systemic formulations disclosed herein, and in particular systemic formulations for oral administration, most preferably comprise at least one acidifying agent and / or at least one polymer precipitation inhibitor. Includes.

[0064] The systemic formulations disclosed herein, and in particular systemic formulations for oral administration, most preferably include adipic acid as an acidifying agent and polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose as polymer precipitation inhibitors.

[0065] Accordingly, embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a polymer precipitation inhibitor.

[0066] Accordingly, embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one polymer precipitation inhibitor, for use in the prevention and / or treatment of celiac disease.

[0067] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein the at least one excipient is a binder / polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is selected from the group comprising or comprising cellulose and cellulose derivatives.

[0068] Preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one polymer precipitation inhibitor selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, and cellulose derivatives.

[0069] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least One excipient is a polymer precipitation inhibitor, where the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and / or hydroxypropylcellulose.

[0070] Embodiments of the present invention thus relate to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one polymer precipitation inhibitor selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and / or hydroxypropylcellulose, for use in the prevention and / or treatment of celiac disease.

[0071] Embodiments of the present invention thus relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and L-hydroxypropylcellulose and / or hydroxypropylcellulose, for use in the prevention and / or treatment of celiac disease.

[0072] The systemic formulations according to the present invention may contain binders. Therefore, excipients can be binders. Binders are characterized as substances that bind or "adhere" powders to each other, and consequently function as "adhesives" in the formulation. Suitable binders include sugars, e.g., sucrose; polysaccharides, e.g., xanthan gum, guar gum, carrageenan, starches derived from wheat, corn, rice, and potatoes, as well as pre-aggregated (modified) starches, sodium starch glycolate, derived from wheat, corn, rice, and potatoes; natural gums, e.g., acacia gum, gelatin, tragacanth; seaweed derivatives, e.g., alginic acid, sodium alginate, and calcium ammonium alginate; cellulose or cellulose derivatives, e.g., hydroxypropylcellulose, L-hydroxypropylcellulose (low-substituted hydroxypropylcellulose), methylcellulose, and sodium carboxymethylcellulose, and hydroxypropylmethylcellulose, or polyvinylpyrrolidone, particularly povidone K25. Preferably, the binder is a polymer, more preferably a gel-forming polymer, and even more preferably cellulose or a cellulose derivative, even more preferably L-hydroxypropylcellulose, most preferably a combination of L-hydroxypropylcellulose and hydroxypropylcellulose. The combination of L-hydroxypropylcellulose and hydroxypropylcellulose also functions as a polymer precipitation inhibitor and a disintegrant.

[0073] Hydroxypropyl cellulose is a partially substituted poly(hydroxypropyl) ether of cellulose. It may contain 0.6% or less silica or other suitable anticoagulants. Hydroxypropyl cellulose is commercially available in numerous different grades with varying solution viscosities. Its molecular weight ranges from 50,000 to 1,250,000. Hydroxypropyl cellulose is partially O-(2-hydroxypropylated)cellulose. Hydroxypropyl cellulose contains 53.4% ​​to 80% hydroxypropoxy groups based on the dry material. It contains 0.5%. The average grade in polymerization is in the range of 200 to 300. The molar grade in substitution is approximately 4. "Low-substituted hydroxypropyl cellulose" (L-HPC or LHPC) is a low-substituted poly(hydroxypropyl) ether of cellulose. "Low-substituted hydroxypropyl cellulose" (L-HPC or LHPC) is commercially available in a number of different grades with different particle sizes and substitution levels.

[0074] Low-substituted hydroxypropyl cellulose contains 5% to 16% hydroxypropoxy groups on a dry basis. The molar grade of substitution is <1. In particular, low-substituted hydroxypropyl cellulose is low-substituted O-(2-hydroxypropylated) cellulose and contains 5.0% to 16.0% or less hydroxypropoxy groups (-OCH2CHOHCH3) on a dry basis.

[0075] "Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus (registered trademark))" has the following chemical structure:

[0076] [ka] It has.

[0077] "Povidone" is used synonymously with polyvinylpyrrolidone (PVP). Polyvinylpyrrolidone consists of a linear polymer of 1-ethenylpyrrolidine-2-one. Various types of polyvinylpyrrolidone are characterized by the viscosity of the polyvinylpyrrolidone solution, expressed by the K value. Polyvinylpyrrolidone exists as a white to yellowish-white powder or flake and is readily soluble in water. The K value is a common classification in the plastics industry and is directly related to the average molar mass of the polymer. This makes it possible to indirectly estimate the degree of polymerization, and therefore the chain length, from the K value. Povidone K25, povidone K30, or povidone K90 are commercially available. Preferably, povidone K25 is used as a binder. The approximate average molecular weight of povidone K25 is 30,000 g / mol (K It is (Da) and ranges from 28,000 g / mol (KDa) to 34,000 g / mol (KDa).

[0078] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a binder.

[0079] Accordingly, preferred embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder, for use in the prevention and / or treatment of celiac disease.

[0080] Accordingly, preferred embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein the at least one excipient is a binder, and the binder is polyvinylpyrrolidone.

[0081] Accordingly, preferred embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one polyvinylpyrrolidone, for use in the prevention and / or treatment of celiac disease.

[0082] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein the at least one excipient is a binder, wherein the binder is polyvinylpyrrolidone, wherein polyvinylpyrrolidone is povidone K25.

[0083] Therefore, preferred embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and povidone K25, for use in the prevention and / or treatment of celiac disease.

[0084] Furthermore, the systemic formulation according to the present invention may include a binder and / or a polymer precipitation inhibitor. Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising binders and polymer precipitation inhibitors.

[0085] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least one polymer precipitation inhibitor, wherein at least one excipient comprises or comprises a binder and a polymer precipitation inhibitor.

[0086] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, where at least one excipient is a binder and a polymer precipitation inhibitor. Preferably, at least one excipient functions simultaneously as a binder and a polymer precipitation inhibitor. Thus, at least one excipient is a binder and a polymer precipitation inhibitor.

[0087] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, as well as a binder and at least one compound that is a polymer precipitation inhibitor.

[0088] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one binder, and at least one polymer precipitation inhibitor.

[0089] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1- The present invention relates to a systemic formulation comprising or comprising methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising a binder and a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, cellulose derivatives, combinations of cellulose and derivatives, or combinations of cellulose derivatives.

[0090] Preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least one polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, cellulose derivatives, combinations of cellulose and derivatives, or combinations of cellulose derivatives.

[0091] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient. Herein, at least one excipient is selected from the group comprising or comprising a binder and a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose.

[0092] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least one polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose.

[0093] Embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, and The present invention relates to a systemic formulation comprising or comprising an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising a binder and a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, or hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, wherein the binder is polyvinylpyrrolidone.

[0094] Embodiments of the present invention relate to systemic formulations comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one polymer precipitation inhibitor selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and hydroxypropylcellulose, and at least one binder selected from L-hydroxypropylcellulose, hydroxypropylcellulose, and hydroxypropylcellulose, and / or polyvinylpyrrolidone.

[0095] Particularly preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a binder and / or at least one excipient is a polymer precipitation inhibitor, wherein the binder / polymer precipitation inhibitor is cellulose, a cellulose derivative, a combination of cellulose and a cellulose derivative, or a combination of cellulose derivatives. The binders are cellulose, cellulose derivatives, combinations of cellulose and derivatives, or combinations of cellulose derivatives, and / or povidone K25.

[0096] Preferred embodiments of the present invention relate to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least one polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, cellulose derivatives, combinations of cellulose and derivatives, or combinations of cellulose derivatives, and the binder is cellulose, cellulose derivatives, combinations of cellulose and derivatives, or combinations of cellulose derivatives, and / or povidone K25.

[0097] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo The present invention relates to a systemic formulation comprising or consisting of sohepto-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and at least one excipient, wherein at least one excipient is a binder and / or at least one excipient is a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose, wherein the binder is L-hydroxypropylcellulose, hydroxypropylcellulose, a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, and / or povidone K25.

[0098] Another preferred embodiment of the present invention relates to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least one polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose, wherein the binder is L-hydroxypropylcellulose, hydroxypropylcellulose, a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, and / or povidone K25.

[0099] Another preferred embodiment of the present invention relates to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a binder, and / or at least one excipient is a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, wherein the binder is povidone K25.

[0100] A preferred embodiment of the present invention relates to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one binder and / or at least a polymer precipitation inhibitor, wherein the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, wherein the binder is povidone K25.

[0101] Data from pharmacokinetic studies in humans support the high relative bioavailability of compound (I). This high relative bioavailability must be understood in comparison to previously conducted animal studies.

[0102] In vivo inhibition of intestinal tissue transglutaminase (TG2) by compounds of formula (I) was demonstrated in a polyinosine:polycytidylic acid (Poly(I:C)) model of small intestinal inflammation. Intestinal TG2 activation was induced within 2–4 hours after administration of Poly(I:C). Inflammation was most pronounced in the jejunum and colon. TG2 activation was upregulated up to 2-fold and up to 4-fold in the small intestine, as occurs in active celiac disease. Administration of the TG2 inhibitor as a plain, unformulated compound was safe and reduced intestinal TG2 activity to normal levels, which was in parallel with suppressed intestinal inflammation (Encalada Ventura et al. 2018).

[0103] The addition of an acidifying agent ensures the complete dissolution of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, in the stomach, but the pH in the duodenum increases from 2 to 6, and therefore the drug may precipitate before reaching or entering the duodenum. To ensure the complete dissolution of the compound, transport to the duodenum, and the drug in a soluble form in the duodenum, the formulation according to the present invention preferably includes an acidifying agent and / or a polymer precipitation inhibitor.

[0104] Pharmacokinetic studies have shown that (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate is absorbed in the duodenum and is sufficient to achieve therapeutically effective drug concentrations in humans at low doses of 20 mg to 50 mg (Example 3, Figure 1).

[0105] Furthermore, no side effects associated with potential off-target effects were observed in humans, even at doses up to 500 mg. This is particularly surprising given that, as mentioned earlier, TG2 is ubiquitous in almost all cell types and cellular compartments, present on the cell surface, secreted into the extracellular matrix, and found in various organs, and therefore is most likely to cause off-target effects.

[0106] Therefore, the systemic formulation according to the present invention may contain an acidifying agent and / or a polymer precipitation inhibitor. Preferably, the systemic formulation comprises an acidifying agent and a polymer precipitation inhibitor.

[0107] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising acidifying agents and polymer precipitation inhibitors.

[0108] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxygen for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising soethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, at least one acidifying agent, and at least one polymer precipitation inhibitor.

[0109] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, and at least one polymer precipitation inhibitor.

[0110] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient. Here, at least one excipient is selected from the group comprising or comprising an acidifying agent and a polymer precipitation inhibitor, wherein the acidifying agent is selected from the group comprising or comprising adipic acid, fumaric acid, and glutaric acid, and the polymer precipitation inhibitor is selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, and cellulose derivatives.

[0111] A preferred embodiment of the present invention comprises (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient for use in the prevention and / or treatment of celiac disease. The subject is a systemic formulation comprising or , wherein at least one excipient is selected from the group comprising an acidifying agent and a polymer precipitation inhibitor, wherein the acidifying agent is adipic acid, and the polymer precipitation inhibitor is selected from the group comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, and cellulose derivatives.

[0112] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one acidifying agent and at least one polymer precipitation inhibitor, wherein the acidifying agent is adipic acid, and the polymer precipitation inhibitor is selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), cellulose, and cellulose derivatives.

[0113] Accordingly, preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one acidifying agent, and a polymer precipitation inhibitor selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and hydroxypropylcellulose.

[0114] Accordingly, preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one acidifying agent, wherein the acidifying agent is selected from the group comprising adipic acid, fumaric acid, and glutaric acid, and at least one polymer precipitation inhibitor is selected from the group comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and hydroxypropylcellulose.

[0115] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, and at least one polymer precipitation inhibitor selected from the group comprising or comprising polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, and hydroxypropylcellulose.

[0116] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein At least one excipient is selected from the group comprising an acidifying agent and a polymer precipitation inhibitor, wherein the acidifying agent is adipic acid, and the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose.

[0117] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2- The present invention relates to a systemic formulation comprising or consisting of oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one acidifying agent and / or at least one polymer precipitation inhibitor, wherein the acidifying agent is adipic acid, and the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose.

[0118] A systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, wherein the systemic formulation is The mixture further comprises at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising an acidifying agent and a polymer precipitation inhibitor, wherein the acidifying agent is selected from the group comprising ascorbic acid, organic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, glutamic acid, etc., and organic tricarboxylic acids such as citric acid, or sodium hydrogen citrate.

[0119] (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, is a systemic formulation for use in the prevention and / or treatment of celiac disease. Herein, the systemic formulation further comprises at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising an acidifying agent and a binder, wherein the acidifying agent is ascorbic acid, organic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, or glutamic acid, and organic tricarboxylic acids such as citric acid. The binder is selected from the group consisting of, or sodium hydrogen citrate, where the binder is selected from the group consisting of, sugars such as sucrose; polysaccharides such as xanthan gum, guar gum, carrageenan, starches derived from wheat, corn, rice and potato, as well as pre-aggregated starches derived from wheat, corn, rice and potato, sodium starch glycolate; polyacrylic acid; natural gums such as acacia gum, gelatin, tragacanth; seaweed derivatives such as alginic acid, sodium alginate and calcium ammonium alginate, cellulose or cellulose derivatives such as hydroxypropylcellulose, L-hydroxypropylcellulose, methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose, or polyvinylpyrrolidone.

[0120] For use in the prevention and / or treatment of celiac disease, the systemic formulations according to the present invention may include an acidifying agent, a polymer precipitation inhibitor, and / or a binder.

[0121] Embodiments of the present invention for use in the prevention and / or treatment of celiac disease include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, The present invention relates to systemic formulations comprising or comprising an enantiomer thereof, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising an acidifying agent, a polymer precipitation inhibitor, and a binder.

[0122] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one acidifying agent, at least one polymer precipitation inhibitor, and at least one binder.

[0123] A more preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, at least one acidifying agent, at least one polymer precipitation inhibitor, and a small amount of The present invention relates to systemic formulations comprising or including at least one binder, wherein the acidifying agent is adipic acid, the polymer precipitation inhibitor is polyvinyl alcohol (PVA), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, and wherein the binder is polyvinylpyrrolidone.

[0124] The systemic formulation according to the present invention may contain a disintegrant. Therefore, excipients can be disintegrants. The term “disintegrant” refers to a material added to a composition to support the disintegration of the formulation and the release of the active pharmaceutical ingredient. Suitable disintegrants include starch, modified starch soluble in cold water, e.g., sodium carboxymethyl starch; cellulose derivatives, e.g., methylcellulose and sodium carboxymethylcellulose; microcrystalline cellulose and cross-linked microcrystalline cellulose, e.g., sodium croscarmellose; alginates, e.g., alginic acid, sodium alginate; clays, e.g., bentonite and effervescent mixtures; effervescent compounds, e.g., citric acid, tartaric acid, sodium citrate, disodium hydrogen citrate, monosodium citrate, sodium bicarbonate and / or This includes combinations such as potassium bicarbonate. Preferably, the disintegrant is croscarmellose sodium.

[0125] Accordingly, embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a disintegrant.

[0126] Therefore, embodiments of the present invention can be used in the prevention and / or treatment of celiac disease. The subject is a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one disintegrant.

[0127] The systemic formulation according to the present invention may contain an acidifying agent, a binder / polymer precipitation inhibitor, and / or a disintegrant. Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, and disintegrants.

[0128] The systemic formulation according to the present invention may contain a lubricant / flow enhancer. Therefore, the excipient can be a lubricant / flow enhancer. The lubricant / flow enhancer is a material that prevents solidification, improves the flow properties of granules, and thus makes the flow smooth and uniform, reduces friction between surfaces in direct contact, and enables tablets, granules, etc., to be released from a mold or press mold after compression by reducing friction.

[0129] Suitable lubricants / flow enhancers include sodium benzoate, metal stearate salts such as magnesium stearate, calcium stearate, or potassium stearate, stearic acid, high-melting-point waxes, inorganic lubricants / flow enhancers such as silicon dioxide and talc, and other substances such as sodium oleate, and polyethylene glycol. Preferably, the lubricant / flow enhancer is talc or silicon dioxide. Since the lubricant / flow enhancer must be present on the surface of the granules and between the granules and the parts of the apparatus, the lubricant / flow enhancer is usually added in the final step before encapsulation or compression.

[0130] Accordingly, preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a lubricant / flow enhancer.

[0131] The systemic formulation according to the present invention may comprise or consist of an acidifying agent, a polymer precipitation inhibitor, a binder, and / or a lubricant / flow enhancer. Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, and lubricants / flow enhancers.

[0132] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, and lubricants / flow enhancers.

[0133] The systemic formulation according to the present invention may comprise or consist of an acidifying agent, a polymer precipitation inhibitor, a binder, a disintegrant, and / or a lubricant / flow enhancer. Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, disintegrants, and lubricants / flow enhancers.

[0134] Furthermore, the systemic formulation according to the present invention may also contain, as excipients, diluents / fillers / binders, sweeteners, flavoring agents, buffers, antioxidants, emulsifiers, solubilizers / humectants, and / or preservatives.

[0135] A suitable diluent / filler / binder is typically a substance that forms the majority of the composition or dosage form. Suitable diluents / fillers / binders include sugars, such as lactose, sucrose, mannitol, and sorbitol; starches derived from wheat, corn, rice, and potatoes; and cellulose, such as microcrystalline cellulose, calcium hydrogen phosphate dihydrate, and calcium sulfate. Preferably, the diluent / filler / binder is cellulose and / or mannitol. Most preferably, the diluent / filler / binder is microcrystalline cellulose and / or mannitol.

[0136] Preferably, the diluent / filler / binder is microcrystalline cellulose when the formulation is a tablet, and mannitol when the formulation is a capsule.

[0137] The addition of mannitol further improves porosity and, therefore, improves the wetting properties of the granules. Systemic formulations for use in the prevention and / or treatment of celiac disease according to the present invention may include diluents / fillers / binders. Preferred embodiments of the present invention relate to systemic formulations comprising or consisting of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is a diluent / filler / binder.

[0138] Systemic formulations according to the present invention for use in the prevention and / or treatment of celiac disease may comprise or consist of an acidifying agent, a polymer precipitation inhibitor, a binder, a disintegrant, a lubricant / flow enhancer, and / or a diluent / filler / binder. Embodiments of the present invention for use in the prevention and / or treatment of celiac disease include (S,E)-methyl The present invention relates to formulations comprising or comprising -7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and at least one excipient, wherein at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, disintegrants, lubricants / flow enhancers, and / or diluents / fillers / binders.

[0139] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one acidifying agent, at least one polymer precipitation inhibitor, at least one binder, at least one disintegrant, at least one lubricant / flow enhancer, and at least one diluent / filler / binder.

[0140] Preferred formulations are provided in an administerable form suitable for oral administration, such as uncoated tablets, coated tablets, effervescent tablets, soluble tablets, chewable tablets, oral lyophilized products, lozenges, pastilles, compressed lozenges, sublingual tablets, oral tablets, granules, effervescent granules, and capsules. More preferably, oral formulations are tablets or capsules. Uncoated tablets, coated tablets, and capsules are most preferably hard or soft pharmaceutical formulations.

[0141] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, wherein the systemic formulation is a tablet, coated tablet, capsule, powder, or granule.

[0142] The systemic formulation according to the present invention may include other components, such as unavoidable impurities and components for capsules, including capsule colorants. Furthermore, in tablets, colorants may be present as other components.

[0143] Furthermore, the ingredients used to coat the tablets are also included in the term "other ingredients." The capsule shell may contain a coloring agent. As used herein, the term "coloring agent" includes pigments such as white pigments. The coloring agent may, among other things, be iron oxide, particularly iron(III) oxide, iron(II,III) oxide, or hydrated ferric oxide, or titanium dioxide.

[0144] "Tablet" means a compressed solid dosage form containing at least an active pharmaceutical ingredient along with appropriate excipients. Tablets can be produced by compressing mixtures or granules obtained by wet granulation, dry granulation, or compression, as is known to those skilled in the art.

[0145] The term "capsule" refers to a special container or shell made of methylcellulose, polyvinyl alcohol, or gelatin, or modified gelatin, or starch, that can encapsulate an activator within the capsule. Typically, hard-shelled capsules contain hydroxypropyl They are prepared from methylcellulose or from a mixture of porcine bone and skin gelatin having relatively high gel strength. The capsule shell may contain small amounts of colorants, opalers, softeners, and preservatives. "Soft-shelled capsules" contain gelatin as the basic polymer, one or more high doses of softeners, such as glycerol or sorbitol, and water. Typically, the amount of softener is 20-30% by weight of the capsule shell, the amount of gelatin is 40-45% by weight of the capsule shell, and the amount of water is 30-35% by weight of the capsule shell. After drying the capsules, the amount of water is 7-8% by weight of the capsule shell.

[0146] The capsule shell may include gelatin, hydroxypropyl methylcellulose (HMPC), polysaccharides such as starch and carrageenan; and / or synthetic polymers such as polyvinyl alcohol copolymers. Furthermore, the capsule shell may contain colorants. As used herein, the term "colorant" includes pigments such as white pigments. Colorants may, among other things, be iron oxides, particularly iron(III) oxide, iron(II,III) oxide, or hydrated ferric oxide, titanium dioxide, natural dyes, azos, and xanthan compounds. Furthermore, the capsule shell may contain preservatives such as p-hydroxybenzoic acid esters, or methods to improve flavor such as ethyl vanillin. Furthermore, the capsule shell may contain surfactants such as sodium lauryl sulfate.

[0147] For compositional purposes, "powder" refers to a powder mixture / blend containing an active ingredient and appropriate excipients that can be suspended in water or juice before use. Spherical granules are also called pellets or beads.

[0148] "Granules" refer to dry, solid particles. Each particle represents an aggregate of powder particles. "Coated drugs" Drug particles are processed by packaging or embedding, but the coating method is related to the dosage form itself. The core of a tablet, sugar-coated tablet, or capsule is coated with a coating layer, where excipients, such as cellulose derivatives, cellulose ethers, such as hydroxypropyl methylcellulose (HMPC), synthetic polymers, corn protein zein, or other polysaccharides, etc. The coating may further contain colorants, such as titanium dioxide, iron(III) oxide, iron(II,III) oxide or hydrated ferric oxide, lactose monohydrate, and / or carnauba wax, etc. Furthermore, capsules may be coated.

[0149] Sustained-release formulations are known in the latest technologies for providing a controlled release rate of any one or more components or active ingredients to optimize therapeutic effects, i.e., inhibitory activity. The pharmacologically optimal concentration is guaranteed with respect to a specific time over the duration of the effect in a single dose. Dosage forms suitable for sustained release include tablets or capsules containing a layer with a changing degradation rate, or a controlled-release polymer matrix impregnated with the active ingredient, and impregnated or encapsulated porous polymer matrix. Sustained-release formulations would hinder the rapid release of the compound. Here, high concentrations of the drug are desired to be rapidly released to the target site after administration. Consequently, since preliminary results show that the formulation cannot provide the high drug concentrations required according to the present invention, sustained-release formulations are undesirable and should be practically avoided for the purposes of the present invention.

[0150] As used herein, the term "rapid release" refers to a duodenum containing (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate as the pharmaceutically active ingredient. This refers to a systemic formulation for targeting the intestinal tract. Therefore, the term "systemic formulation for rapid release" refers to a systemic formulation for the release of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate into the duodenal tract, preferably within 30 minutes, more preferably within 25 minutes, even more preferably within 20 minutes, and even more preferably within 15 minutes, and preferably for complete release.

[0151] The systemic formulation according to the present invention may be in the form of a capsule or a tablet, i.e., the activator and excipients may be filled into the capsule. Embodiments of the present invention are systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or including (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, wherein the systemic formulation is in the form of a capsule or a tablet.

[0152] A preferred embodiment of the present invention is a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising an acidifying agent and a polymer precipitation inhibitor, wherein the systemic formulation is in the form of a capsule or tablet.

[0153] Another preferred embodiment of the present invention is a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, and binders, wherein the systemic formulation is in the form of a capsule or tablet.

[0154] Another preferred embodiment of the present invention is a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one acidifying agent, at least one polymer precipitation inhibitor, and at least one binder, wherein the systemic formulation is in the form of a capsule or a tablet.

[0155] Another preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein At least one excipient is selected from the group comprising or consisting of acidifying agents, polymer precipitation inhibitors, binders, disintegrants, and lubricants / flow enhancers, where the systemic formulation is in the form of a capsule or tablet.

[0156] Another preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, at least one acidifying agent, at least one polymer precipitation inhibitor, at least one binder, at least one disintegrant, and at least one lubricant / flow enhancer, wherein the systemic formulation is in the form of a capsule or tablet.

[0157] Another preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and at least one excipient, wherein the at least one excipient is selected from the group comprising or comprising acidifying agents, polymer precipitation inhibitors, binders, disintegrants, lubricants / flow enhancers, and diluents / fillers / binders, wherein the systemic formulation is in the form of a capsule or a tablet.

[0158] Another preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, at least one acidifying agent, at least one polymer precipitation inhibitor, at least one binder, at least one disintegrant, at least one lubricant / flow enhancer, and at least one diluent / filler / binder, wherein the systemic formulation is in the form of a capsule or tablet.

[0159] The preferred pharmaceutical formulation is for oral administration. Therefore, the preferred pharmaceutical formulation is a systemic formulation in the form of an enteral formulation for oral administration. As a result, capsules and tablets in particular are the most preferred enteral or parenteral formulations for oral administration, and in particular capsules and tablets that ensure high drug concentration by ensuring the rapid release of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate.

[0160] Furthermore, an orally administered pharmaceutical formulation containing adipic acid is preferred. More preferably, a systemic formulation in the form of an orally administered enteral or parenteral formulation containing adipic acid. Most preferably, an orally administered capsule or tablet containing (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, and adipic acid.

[0161] Furthermore, specific PSD (particle size distribution) and / or PSR (particle size range) can be adapted to further improve the performance of the formulation. Therefore, embodiments of the present invention are for use in the prevention and / or treatment of celiac disease, formula (I):

[0162] [ka] The subject is a systemic formulation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or a solvate, hydrate, or pharmaceutically acceptable salt of formula (I), wherein the particles of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate have a particle size range of 0.1 μm to 100 μm.

[0163] The particle size of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, is preferably in the range of 0.1 μm to 100 μm, more preferably in the range of 0.5 μm to 50 μm, and more preferably in the range of 1.0 μm to 20 μm. Therefore, the particle size range (PSR) of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, is 0.1 μm to 100 μm, 0.5 μm to 50 μm, or 1.0 μm to 20 μm. Preferably, the particle size of the drug according to formula (I) is 10 μm or less.

[0164] Another preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable substances, for use in the prevention and / or treatment of celiac disease. A systemic preparation comprising or consisting of a salt, adipic acid, and L-hydroxypropylcellulose, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size range of 0.1 μm to 100 μm.

[0165] Therefore, embodiments of the present invention are for use in the prevention and / or treatment of celiac disease, formula (I):

[0166] [ka] The subject is a systemic preparation containing (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt of formula (I), where (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro The (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by d(0.95) ≤ 25 μm, where (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate is preferably micronized.

[0167] Furthermore, (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, are preferably d(0.1) 0.1 μm to 5 μm. The micrometers are characterized by m, d(0.5) 0.3 μm to 10 μm, d(0.95) 3 μm to 25 μm, more preferably d(0.1) 0.2 μm to 3 μm, d(0.5) 0.4 μm to 7.5 μm, and d(0.95) 2 μm to 15 μm, and most preferably d(0.1) 0.3 μm to 3 μm, d(0.5) 0.5 μm to 5 μm, and d(0.95) 1 μm to 10 μm.

[0168] The particle size distribution is measured by laser diffraction (Malvern analysis, using samples dispersed in n-hexane and sorbitan monooleate). Therefore, the laser light is scattered in a particle size-dependent manner, resulting in a diffraction pattern. From the angle-dependent scattered light intensity, the particle size can be calculated.

[0169] The parameter d(0.1) refers to the diameter of particles that, when 10% of the total volume of a sample is analyzed by laser diffraction (Malvern analysis, sample dispersed in n-hexane and sorbitan monooleate), have a diameter smaller than the indicated value or range of values. Therefore, d(0.1) = 0.1 μm to 5 μm means that the upper limit of the particle size range defining 10% of the smallest particles in the sample is between 0.1 μm and 5 μm. Thus, 10% of all particles have a particle size of d(0.1) or less, and in this case, 10% of all particles have a maximum size between 0.1 μm and 5 μm. It means having

[0170] Consequently, the parameter d(0.5) refers to the diameter of particles that, when 50% of the total volume of the sample is analyzed by laser diffraction (Malvern analysis, sample dispersed in n-hexane and sorbitan monooleate), have a diameter smaller than the indicated value or range of values. Therefore, d(0.5) = 0.3 μm to 10 μm means that the upper limit of the particle size range defining 50% of the smallest particles in the sample is between 0.3 μm and 10 μm. Thus, 50% of all particles have a particle size of d(0.5) or less, and in this case, 50% of all particles have a maximum size between 0.3 μm and 10 μm.

[0171] Consequently, the parameter d(0.95) refers to the diameter of particles that, when 95% of the total volume of particles in the sample are analyzed by laser diffraction (Malvern analysis, sample dispersed in n-hexane and sorbitan monooleate), have a diameter smaller than the indicated value or range of values. Therefore, d(0.95) = 3 μm to 25 μm means that the upper limit of the particle size range defining 95% of the smallest particles in the sample is between 3 μm and 25 μm. Thus, 95% of all particles have a particle size of d(0.95) or less, and in this case, 95% of all particles have a maximum size between 3 μm and 25 μm.

[0172] Other embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipine, for use in the prevention and / or treatment of celiac disease. The subject is a systemic formulation comprising or comprising an acid and L-hydroxypropylcellulose, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by d(0.95) ≤ 25 μm.

[0173] A preferred embodiment of the present invention comprises or consists of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease. The subject is a embodied formulation, where (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by d(0.1) 0.1 μm to 5 μm, d(0.5) 0.3 μm to 10 μm, and d(0.95) 3 μm to 25 μm.

[0174] A more preferred embodiment of the present invention is a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, adipic acid, and L-hydroxypropylcellulose, wherein1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, adipic acid, and L-hydroxypropylcellulose, where (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-1,2-dihydropyridine-3-ylamino) The particles of (no)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate have a particle size distribution defined by d(0.1) 0.1 μm to 5 μm, d(0.5) 0.3 μm to 10 μm, and d(0.95) 3 μm to 25 μm.

[0175] A more preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, and L-hydroxypropyl ethyl acetate for use in the prevention and / or treatment of celiac disease. A systemic preparation comprising or comprising lurose, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by d(0.1) 0.2 μm to 3 μm, d(0.5) 0.4 μm to 7.5 μm, and d(0.95) 2 μm to 15 μm.

[0176] A more preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, L-hydroxypropylcellulose, croscarmellol, for use in the prevention and / or treatment of celiac disease. A systemic preparation comprising or consisting of sodium and talc, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by d(0.1) 0.2 μm to 3 μm, d(0.5) 0.4 μm to 7.5 μm, and d(0.95) 2 μm to 15 μm.

[0177] A particularly preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, L-hydroxypropylcellulose, croscarmellose, for use in the prevention and / or treatment of celiac disease. A systemic preparation comprising or consisting of thorium, talc, and titanium dioxide, wherein (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate has a particle size distribution defined by d(0.1) 0.1 μm to 5 μm, d(0.5) 0.3 μm to 10 μm, and d(0.95) 3 μm to 25 μm.

[0178] Another particularly preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of adipic acid, L-hydroxypropylcellulose, povidone K25, croscarmellose sodium, microcrystalline cellulose, and silicon dioxide, wherein (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, has a particle size distribution defined by d(0.1) 0.1 μm to 5 μm, d(0.5) 0.3 μm to 10 μm, and d(0.95) 3 μm to 25 μm.

[0179] Therefore, embodiments of the present invention are for use in the prevention and / or treatment of celiac disease, formula (I):

[0180] [ka] The subject is a systemic preparation containing (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt of formula (I), where, (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by a particle size range of 0.1 μm to 100 μm and d(0.95) ≤ 25 μm.

[0181] Therefore, preferably, a systemic preparation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, for use in the prevention and / or treatment of celiac disease. The agent is, where (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, is in the form of particles having a particle size distribution defined by d(0.95) ≤ 25 μm.

[0182] A preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease. A systemic formulation comprising or including dipic acid and L-hydroxypropylcellulose, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by a particle size range of 0.1 μm to 100 μm and d(0.95) ≤ 25 μm.

[0183] A more preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, L-hydroxypropylcellulose, hydroxypropyl A systemic preparation comprising or consisting of cellulose, mannitol, croscarmellose sodium, and talc, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by a particle size range of 0.1 μm to 100 μm and d(0.95) ≤ 25 μm.

[0184] A particularly preferred embodiment of the present invention is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, adipic acid, L-hydroxypropylcellulose, hydroxypropylcellulose, for use in the prevention and / or treatment of celiac disease. A systemic preparation comprising or consisting of mannitol, croscarmellose sodium, talc, gelatin, and titanium dioxide, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size distribution defined by a particle size range of 0.1 μm to 100 μm and d(0.95) ≤ 25 μm.

[0185] In addition to the present invention, particularly preferred embodiments include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, adipic acid, L-hydroxypropylcellulose, and povidone K25 for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of croscarmellose sodium, microcrystalline cellulose, and silicon dioxide, wherein the (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate particles have a particle size range of 0.1 μm to 100 μm and a particle size distribution defined by d(0.95) ≤ 25 μm.

[0186] Systemic formulations include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts. Each formulation contains at least 0.01 mg, preferably at least 0.1 mg, more preferably at least 0.5 mg, even more preferably at least 1 mg, even more preferably at least 2 mg, even more preferably at least 3 mg, even more preferably at least 4 mg, even more preferably at least 5 mg, even more preferably 0.01 mg to 1000 mg, even more preferably 0.05 mg to 900 mg, even more preferably 0.10 mg to 800 mg, even more preferably 0.2 mg to 700 mg, even more preferably 0.3 mg to 600 mg, even more preferably 0.4 mg to 500 mg, even more preferably 0.5 mg to 500 mg, even more preferably 0.6 mg to 450 mg, and even more preferably 0.7 mg. It may contain 400 mg, more preferably 0.8 mg to 375 mg, more preferably 0.9 mg to 350 mg, more preferably 1.0 mg to 300 mg, more preferably 1.25 mg to 300 mg, more preferably 1.5 mg to 275 mg, more preferably 1.75 mg to 250 mg, more preferably 2.0 mg to 225 mg, more preferably 2.25 mg to 220 mg, more preferably 2.5 mg to 220 mg, more preferably 2.75 mg to 215 mg, more preferably 3.0 mg to 210 mg, more preferably 3.75 mg to 205 mg, more preferably 4.0 mg to 205 mg, 4.5 mg to 200 mg, and most preferably 5 mg to 200 mg.

[0187] The systemic formulation contains (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, solvate, or hydrate, in an amount from 0.1 wt% to 99 wt%, preferably 0 0.2 wt% to 90 wt%, more preferably 0.3 wt% to 85 wt%, even more preferably 0.4 wt% to 80 wt%, even more preferably 0.5 wt% to 75 wt%, even more preferably 0.6 wt% to 70 wt%, even more preferably 0.7 wt% to 65 wt%, even more preferably 0.8 wt% to 60 wt%, even more preferably 0.9 wt% to 55 wt%, and even more preferably 1 wt% to 50 wt% It can be contained in amounts of, more preferably 1 wt% to 45 wt%, more preferably 1.25 wt% to 45 wt%, more preferably 1.5 wt% to 40 wt%, more preferably 1.75 wt% to 35 wt%, more preferably 2 wt% to 34 wt%, more preferably 2.25 wt% to 33 wt%, more preferably 2.5 wt% to 32 wt%, and most preferably 2.5 wt% to 31 wt%, more preferably 2.5 wt% to 30.5 wt%, and more preferably 2.6 wt% to 30.3 wt%, more preferably 3 wt% to 30 wt%, more preferably 3.5 wt% to 29 wt%, more preferably 4 wt% to 28 wt%, more preferably 4 wt% to 27 wt%, more preferably 4.5 wt% to 27 wt%, and most preferably 5 wt% to 27 wt%. "Wt%" (weight percentage) refers to the weight percentage of the composition.

[0188] The amount of acidifying agent is 0.1 wt% to 80 wt%, preferably 0.5 wt% to 77.5 wt%, more preferably 1 wt% to 75 wt%, more preferably 1.5 wt% to 72.5 wt%, more preferably 2 wt% to 70 wt%, more preferably 2.5 wt% to 62.5 wt%, more preferably 3 wt% to 57.5 wt%, more preferably 3.5 wt% to 55 wt%, even more preferably 4 wt% to 55 wt%, and even more preferably 4 The range can be 0.5 wt% to 55 wt%, more preferably 5 wt% to 54 wt%, more preferably 5.5 wt% to 53 wt%, more preferably 6 wt% to 52 wt%, more preferably 6.5 wt% to 51 wt%, more preferably 7 wt% to 50 wt%, more preferably 8 wt% to 49 wt%, more preferably 8.5 wt% to 49 wt%, and most preferably 9 wt% to 49 wt%.

[0189] Furthermore, the amount of acidifying agent is 1.00 mg to 500 mg, more preferably 1.25 mg to 495 mg, even more preferably 1.50 mg to 490 mg, even more preferably 1.75 mg to 485 mg, even more preferably 2.00 mg to 480 mg, even more preferably 2.25 mg to 475 mg, even more preferably 2.50 mg to 470 mg, even more preferably 3.0 mg to 465 mg, even more preferably 3.25 mg to 460 mg, even more preferably 3.5 mg to 455 mg, even more preferably 3.75 mg to 450 mg, even more preferably 4.00 mg to 445 mg, even more preferably 4.25 mg to 440 mg, even more preferably 4.5 mg to 435 mg, even more preferably 4.75 mg to 430 mg, even more preferably 5.0 mg to 425 mg, even more preferably 5.25 mg to 420 mg, even more preferably 5.5 mg to 415 mg, and even more Preferably, the range is 5.75 mg to 410 mg, more preferably 6.0 mg to 410 mg, more preferably 6.25 mg to 405 mg, more preferably 6.5 mg to 400 mg, more preferably 6.75 mg to 395 mg, more preferably 7.0 mg to 390 mg, more preferably 7.5 mg to 390 mg, more preferably 7.75 mg to 385 mg, more preferably 8.0 mg to 380 mg, more preferably 8.5 mg to 375 mg, more preferably 9 mg to 370 mg, more preferably 9 mg to 365 mg, more preferably 9 mg to 360 mg, more preferably 9 mg to 350 mg, more preferably 9 mg to 325 mg, more preferably 9 mg to 300 mg, more preferably 9 mg to 250 mg, more preferably 9 mg to 200 mg, and most preferably in the range of 9 mg to 180 mg.Furthermore, the mass ratio of the acidifying agent to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt is 15 to 0.1 m / m, preferably 14.5 to 0.2 m / m, more preferably 14.0 to 0.3 m / m, even more preferably 13.5 to 0.4 m / m, even more preferably 13.0 to 0.5 m / m, even more preferably 12.5 to 0.6 m / m, and even more Preferably, the size can be in the range of 12.0 to 0.7 mm, more preferably 11.75 to 0.8 mm, more preferably 11.5 to 0.9 mm, more preferably 11.5 to 1.0 mm, more preferably 11.5 to 1.1 mm, more preferably 11.5 to 1.2 mm, more preferably 11.5 to 1.3 mm, more preferably 11.5 to 1.4 mm, more preferably 11.5 to 1.5 mm, more preferably 11.5 to 1.6 mm, more preferably 11.5 to 1.7 mm, more preferably 11.5 to 1.8 mm, and most preferably in the range of 2 to 1 mm.

[0190] The amount of binder / polymer precipitation inhibitor can be varied from 0.1 wt% to 40 wt%, preferably 0.5 wt% to 39 wt%, more preferably 1 wt% to 38 wt%, even more preferably 1.25 wt% to 38 wt%, even more preferably 1.5 wt% to 37 wt%, even more preferably 1.75 wt% to 36 wt%, even more preferably 2 wt% to 35 wt%, even more preferably 1.5 wt% to 34 wt%, even more preferably 1.6 wt% to 33 wt%, even more preferably 1.7 wt% to 32 wt%, even more preferably 1.8 wt% to 31 wt%, even more preferably 3.5 wt% to 30 wt%, even more preferably 4 wt% to 29 wt%, even more preferably 4.5 wt% to 28.5 wt%, and most preferably 5 wt% to 28.5 wt%.

[0191] Furthermore, the amount of polymer precipitation inhibitor is 1 mg to 100 mg, preferably 1.5 mg to 95 mg, more preferably 2 mg to 92.5 mg, and even more preferably 2.5 mg. The amount can range from 90 mg, more preferably from 3 mg to 87.5 mg, more preferably from 3.5 mg to 85 mg, more preferably from 4 mg to 82.5 mg, more preferably from 4.5 mg to 80 mg, more preferably from 5 mg to 77.5 mg, more preferably from 5.5 mg to 75 mg, from 6 mg to 72.5 mg, more preferably from 6.5 mg to 70 mg, more preferably from 7 mg to 65 mg, more preferably from 7.5 mg to 62.5 mg, more preferably from 8 mg to 60 mg, more preferably from 8.5 mg to 57.5 mg, more preferably from 9 mg to 55 mg, more preferably from 9.5 mg to 52.5 mg, more preferably from 9.75 mg to 52.5 mg, and most preferably in the range of 10 mg to 50 mg.

[0192] Furthermore, the mass ratio of the polymer precipitation inhibitor to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, is 0.05 to 10 m / m, preferably 0.06 to 9.5 m / m, more preferably 0.07 to 9.00 m / m, even more preferably 0.08 to 8.5 m / m, and even more preferably 0.09 m / m. The thickness can range from 8.00 mm to 7.5 mm, more preferably from 0.1 to 7.25 mm, more preferably from 0.12 to 7.00 mm, more preferably from 0.13 to 6.75 mm, more preferably from 0.14 to 6.5 mm, more preferably from 0.15 to 6.25 mm, more preferably from 0.16 to 6.00 mm, more preferably from 0.17 to 5.75 mm, more preferably from 0.18 to 5.5 mm, more preferably from 0.19 to 5.25 mm, and most preferably in the range of 0.2 to 5 mm.

[0193] The amount of binder can be varied from 0 wt% to 40 wt%, preferably from 0 wt% to 35 wt%, more preferably from 0 wt% to 30 wt%, even more preferably from 0 wt% to 25 wt%, even more preferably from 0 wt% to 20 wt%, even more preferably from 0 wt% to 15 wt%, even more preferably from 0 wt% to 12 wt%, and most preferably from 0 wt% to 8.5 wt%.

[0194] Furthermore, the amount of binder is 1.00 mg to 100 mg, preferably 1.50 mg to 95 mg, more preferably 2.00 mg to 92.5 mg, even more preferably 2.50 mg to 90 mg, even more preferably 3.00 mg to 87.5 mg, even more preferably 3.50 mg to 85 mg, even more preferably 4.00 mg to 82.5 mg, even more preferably 4.50 mg to 80 mg, even more preferably 5.00 mg to 77.5 mg, even more preferably 5.50 mg to 75 mg, 6.00 The range can be from mg to 72.5 mg, more preferably 6.50 mg to 70 mg, more preferably 7.00 mg to 65 mg, more preferably 7.50 mg to 62.5 mg, more preferably 8.00 mg to 60 mg, more preferably 8.50 mg to 57.5 mg, more preferably 9.00 mg to 55.0 mg, more preferably 9.50 mg to 52.5 mg, more preferably 9.75 mg to 52.5 mg, and most preferably in the range of 10 mg to 50 mg.

[0195] Furthermore, the mass ratio of the binder to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, is 0 to 10 m / m, preferably 0.05 to 9.5 m / m, more preferably 0.06 to 9.00 m / m, and even more preferably 0.07 to 8.50 m / m. / m, more preferably 0.08 to 8.00 mm / m, more preferably 0.09 to 7.5 mm / m, more preferably 0.1 to 7.25 mm / m, even more preferably 0.11 to 7.00 mm / m, even more preferably 0.12 to 6.75 mm / m, even more preferably 0.13 to 6.50 mm / m, even more preferably 0.14 to 6.25 mm / m, even more preferably 0.15 to 6.00 mm / m, even more preferably 0.16 to 5.75 mm / m, and even more preferably 0. The range can be 17 to 5.50 mm, more preferably 0.18 to 5.25 mm, more preferably 0.19 to 5.5 mm, more preferably 0.20 to 5 mm, more preferably 0.20 to 4.5 mm, more preferably 0.20 to 4 mm, more preferably 0.20 to 3.5 mm, more preferably 0.20 to 3 mm, more preferably 0.20 to 2.5 mm, and more preferably 0.20 to 2 mm.

[0196] The amount of disintegrant can vary from 0.1 wt% to 40 wt%, preferably 1 wt% to 35 wt%, more preferably 2 wt% to 30 wt%, more preferably 2.5 wt% to 29 wt%, more preferably 3.0 wt% to 28 wt%, more preferably 3.5 wt% to 27 wt%, and most preferably 3.5 wt% to 26.5 wt%.

[0197] Furthermore, the amount of disintegrant is 0.1 mg to 150 mg, preferably 0.50 mg to 145 mg, more preferably 0.75 mg to 140 mg, even more preferably 1.00 mg to 135 mg, even more preferably 1.25 mg to 130 mg, even more preferably 1.50 mg to 125 mg, even more preferably 1.75 mg to 120 mg, even more preferably 2.00 mg to 115 mg, even more preferably 2.25 mg to 110 mg, even more preferably 2.50 mg to 105 mg, even more preferably 2.75 mg to 100 mg, even more preferably 3.00 mg to 95 mg, even more preferably 3.25 mg to 90 mg, even more preferably 3.50 mg to 85 mg, even more preferably 3.75 mg to 80 mg, and even more The amount can be varied preferably from 4.00 mg to 75 mg, more preferably from 4.25 mg to 70 mg, more preferably from 4.50 mg to 65 mg, more preferably from 4.75 mg to 60 mg, more preferably from 5.00 mg to 55 mg, more preferably from 5.50 mg to 50 mg, more preferably from 6.00 mg to 45 mg, more preferably from 6.50 mg to 42.5 mg, more preferably from 7.00 mg to 40 mg, more preferably from 7.50 mg to 40 mg, more preferably from 8.00 mg to 40 mg, more preferably from 8.50 mg to 40 mg, more preferably from 9.00 mg to 40 mg, more preferably from 9.50 mg to 40 mg, and most preferably from 10 mg to 40 mg.

[0198] Furthermore, the mass ratio of the disintegrant to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt is 0.05 to 12 m / m, preferably 0.06 to 11.5 m / m, more preferably 0.07 to 11 m / m, even more preferably 0.08 to 10.5 m / m, and even more preferably 0 The range is 0.09 to 10 mm, more preferably 0.1 to 9.5 mm, more preferably 0.11 to 9 mm, more preferably 0.12 to 8.5 mm, more preferably 0.13 to 8 mm, more preferably 0.14 to 7.5 mm, more preferably 0.15 to 7 mm, more preferably 0.16 to 6.5 mm, more preferably 0.17 to 5.5 mm, more preferably 0.18 to 5 mm, more preferably 0.19 to 5 mm, and most preferably in the range of 0.2 to 5 mm.

[0199] The amount of lubricant / flow enhancer can be in the range of 0.1 wt% to 10 wt%, preferably more preferably 0.25 wt% to 9.5 wt%, even more preferably 0.5 wt% to 9 wt%, even more preferably 0.75 wt% to 8.5 wt%, even more preferably 1 wt% to 8 wt%, even more preferably 1.25 wt% to 7.5 wt%, even more preferably 1.5 wt% to 7 wt%, and even more preferably 1.5 wt% to 6.5 wt%.

[0200] Furthermore, the amount of lubricant / flow enhancer is 0.01 mg to 100 mg, preferably 0.05 mg to 95 mg, more preferably 0.1 mg to 90 mg, even more preferably 0.3 mg to 85 mg, even more preferably 0.4 mg to 80 mg, even more preferably 0.5 mg to 0.6 mg, even more preferably 0.7 mg to 70 mg, even more preferably 0.8 mg to 65 mg, even more preferably 0.9 mg to 60 mg, even more preferably 1 mg to 55 mg, even more preferably 1.1 mg to 50 mg, and even more preferably 1.2 mg The amount can range from mg to 45 mg, more preferably 1.3 mg to 40 mg, more preferably 1.4 mg to 35 mg, more preferably 1.5 mg to 30 mg, more preferably 1.6 mg to 25 mg, more preferably 1.7 mg to 20 mg, more preferably 1.8 mg to 20 mg, more preferably 1.9 mg to 20 mg, more preferably 2 mg to 20 mg, more preferably 3 mg to 20 mg, more preferably 4 mg to 20 mg, and most preferably, more preferably, in the range of 5 mg to 20 mg.

[0201] Furthermore, the mass ratio of the lubricant / flow enhancer to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, can be in the range of 0.05 to 2 m / m, preferably 0.06 to 1.8 m / m, more preferably 0.07 to 1.6 m / m, 0.08 to 1.4 m / m, even more preferably 0.09 to 1.3 m / m, and most preferably 0.1 to 1.2 m / m.

[0202] The amount of diluent / filler / binder in the composition can be in the range of 0 wt% to 50% wt%, preferably 1 wt% to 47.5% wt%, more preferably 1.5 wt% to 45% wt%, more preferably 2 wt% to 42.5% wt%, more preferably 2.5 to 40 wt%, more preferably 3 wt% to 38% wt%, more preferably 3.5 wt% to 38 wt%, more preferably 4 wt% to 38 wt%, more preferably 4.5 wt% to 38 wt%, and even more preferably 5 wt% to 38 wt%.

[0203] Furthermore, the amount of diluent / filler / binder is 1 mg to 290 mg, preferably 2 mg to 280 mg, more preferably 3 mg to 270 mg, even more preferably 4 mg to 260 mg, even more preferably 5 mg to 250 mg, even more preferably 6 mg to 240 mg, even more preferably 7 mg to 230 mg, even more preferably 8 mg to 220 mg, even more preferably 9 mg to 210 mg, even more preferably 10 mg to 200 mg, even more preferably 11 mg to 190 mg, and even more preferably 12 mg. From 180 mg, more preferably 13 mg to 170 mg, more preferably 14 mg to 160 mg, more preferably 15 mg to 150 mg, more preferably 16 mg to 140 mg, more preferably 17 mg to 130 mg, more preferably 18 mg to 120 mg, more preferably 19 mg to 110 mg, more preferably 19 mg to 100 mg, more preferably 20 mg to 90 mg, more preferably 21 mg to 80 mg, more preferably 22 mg to 70 mg, and even more preferably The dose can be in the range of 23 mg to 60 mg, more preferably 24 mg to 55 mg, and most preferably 25 mg to 50 mg.

[0204] Furthermore, the mass ratio of the diluent / filler / binder to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, is 0. The range can be from 0.1 mm to 17.5 mm, more preferably from 0.05 mm to 15 mm, more preferably from 0.1 mm to 0.125 mm, more preferably from 0.15 mm to 10 mm, more preferably from 0.175 mm to 7.5 mm, more preferably from 0.2 mm to 6 mm, more preferably from 0.2 mm to 5.5 mm, and more preferably from 0.2 mm to 5 mm.

[0205] The amounts of other components can range from 5 wt% to 60 wt%, preferably 6 wt% to 57.5 wt%, more preferably 7 wt% to 55 wt%, even more preferably 8 wt% to 52.5 wt%, even more preferably 9 wt% to 51 wt%, and most preferably 10 wt% to 50 wt% relative to the dosage form.

[0206] Furthermore, the amounts of other components can range from 50 mg to 200 mg, preferably 55 mg to 190 mg, more preferably 60 mg to 180 mg, even more preferably 65 mg to 170 mg, even more preferably 70 mg to 160 mg, even more preferably 75 mg to 150 mg, even more preferably 80 mg to 140 mg, even more preferably 90 mg to 130 mg, even more preferably 90 mg to 120 mg, even more preferably 90 mg to 110 mg, and most preferably 90 mg to 100 mg.

[0207] Furthermore, the mass ratio of the capsule to the mass of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, can be in the range of 0 to 30 m / m, preferably 0.2 to 27.5 m / m, more preferably 0.3 to 25 m / m, even more preferably 0.35 to 22.5 m / m, even more preferably 0.4 to 21 m / m, and most preferably 0.45 to 20 m / m.

[0208] Embodiments of the present invention relate to systemic formulations comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease.

[0209] Embodiments of the present invention relate to systemic formulations comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease.

[0210] Embodiments of the present invention relate to systemic formulations comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, for use in the prevention and / or treatment of celiac disease.

[0211] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, and 1 wt% to 75 wt% of an acidifying agent.

[0212] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, and 3 wt% to 75 wt% of an acidifying agent.

[0213] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 4.5 wt% to 55 wt% of an acidifying agent.

[0214] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 1 wt% to 75 wt% of an acidifying agent.

[0215] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3 wt% to 75 wt% of an acidifying agent.

[0216] Embodiments of the present invention include, for use in the prevention and / or treatment of celiac disease, 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 4.5 wt% to 55 wt% of an acidifying agent, or a systemic solution comprising Regarding sexually transmitted drugs.

[0217] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 1 wt% to 75 wt% of an acidifying agent.

[0218] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3 wt% to 75 wt% of an acidifying agent.

[0219] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 4.5 wt% to 55 wt% of an acidifying agent.

[0220] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and 1 wt% to 75 wt% of an acidifying agent.

[0221] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, and 3 wt% to 75 wt% of an acidifying agent.

[0222] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 4.5 wt% to 55 wt% of an acidifying agent.

[0223] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 1 wt% to 75 wt% adipic acid.

[0224] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 3 wt% to 75 wt% adipic acid.

[0225] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 4.5 wt% to 55 wt% adipic acid.

[0226] A more preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 1 wt% to 75 wt% of adipic acid.

[0227] A more preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 3 wt% to 75 wt% of adipic acid.

[0228] A more preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 4.5 wt% to 55 wt% of adipic acid.

[0229] A preferred embodiment of the present invention is a 0.1 wt% to 45 wt% (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceuticals for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a scientifically acceptable salt and 5 wt% to 50 wt% adipic acid.

[0230] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 3 wt% to 75 wt% of adipic acid.

[0231] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 4.5 wt% to 55 wt% of adipic acid.

[0232] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 1 wt% to 75 wt% of adipic acid.

[0233] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3 wt% to 75 wt% of adipic acid.

[0234] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 4.5 wt% to 55 wt% of adipic acid.

[0235] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0236] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0237] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0238] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0239] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3.5 wt% to 35 wt% of a polymer precipitation inhibitor.

[0240] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 2 wt% to 30 wt% of a polymer precipitation inhibitor.

[0241] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0242] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising hept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0243] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0244] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0245] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0246] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0247] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0248] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose and relate to a systemic formulation.

[0249] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, (S,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 3.5 wt% to 30 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0250] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, 0.1 wt% to 80 wt% (S,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0251] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising, or consisting of, 0.1 wt% to 80 wt% (S,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, and 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0252] Preferred embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3.5 wt% to 30 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0253] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0254] A preferred embodiment of the present invention is 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7 for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of oxohepto-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, and 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0255] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3.5 wt% to 30 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0256] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0257] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0258] A preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, and 3.5 wt% to 30 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0259] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0260] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0261] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0262] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0263] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0264] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0265] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0266] Embodiments of the present invention relate to (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl- The present invention relates to a systemic formulation comprising or comprising 1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0267] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0268] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0269] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0270] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or consisting of 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0271] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or consisting of 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0272] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate, or an enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor, or consisting of the foregoing.

[0273] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0274] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0275] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0276] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0277] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0278] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0279] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0280] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0281] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0282] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0283] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0284] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0285] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0286] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0287] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0288] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0289] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0290] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0291] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3- for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0292] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of a polymer precipitation inhibitor.

[0293] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 2 wt% to 35 wt% of a polymer precipitation inhibitor.

[0294] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, and 3.5 wt% to 30 wt% of a polymer precipitation inhibitor.

[0295] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0296] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, and 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0297] Embodiments of the present invention relate to (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl- The present invention relates to a systemic formulation comprising or consisting of 1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, and 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0298] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% adipic acid, and 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0299] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% adipic acid, and 2 wt% to 35 t% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0300] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% adipic acid, and 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0301] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% adipic acid, and 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0302] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% adipic acid, and 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0303] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% adipic acid, and 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0304] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0305] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0306] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0307] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0308] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of hept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% adipic acid, and 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0309] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0310] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0311] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0312] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0313] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0314] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0315] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0316] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0317] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0318] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0319] Embodiments of the present invention relate to 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable substances, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a tolerable salt, 4.5 wt% to 55 wt% adipic acid, and 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0320] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0321] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0322] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0323] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0324] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0325] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0326] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0327] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0328] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, and 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0329] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0330] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 3.5 wt% to 3 The present invention relates to a systemic formulation comprising or consisting of 0.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0331] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 15 wt% of a binder.

[0332] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0333] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, and 0 wt% to 12 wt% binder.

[0334] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0335] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, and 0 wt% to 12 wt% binder.

[0336] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, and 0 wt% to 12 wt% binder.

[0337] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0338] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0339] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0340] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0341] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0342] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0343] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0344] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0345] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0346] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0347] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0348] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of hept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0349] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0350] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0351] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0352] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0353] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0354] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0355] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0356] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0357] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0358] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0359] Embodiments of the present invention relate to 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically appropriate compounds, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising an acceptable salt, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0360] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0361] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0362] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0363] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0364] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0365] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0366] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0367] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0368] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 15 wt% povidone K25.

[0369] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0370] Embodiments of the present invention provide (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose, and for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of hydroxypropyl cellulose and 0 wt% to 12 wt% povidone K25.

[0371] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0372] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0373] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0374] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0375] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0376] Embodiments of the present invention relate to (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising )-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0377] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0378] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0379] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of adipic acid, and 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

[0380] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 1 wt% to 75 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0381] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, and 0.1 wt% to 40 wt% of L- The present invention relates to a systemic formulation comprising or consisting of hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0382] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0383] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0384] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0385] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0386] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0387] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0388] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0389] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0390] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0391] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0392] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-yl for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising amino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0393] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0394] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0395] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0396] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0397] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-ethyl for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising xohepto-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0398] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, and 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0399] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0400] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 3 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0401] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0402] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of adipic acid, and 0.1 wt% to 40 wt% The present invention relates to a systemic formulation comprising or comprising % L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K25.

[0403] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0404] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0405] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 15 wt% binder, 0.1 wt% to 35 wt% disintegrant, and 0.1 wt% to 10 wt% lubricant / flow enhancer.

[0406] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0407] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0408] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0409] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0410] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0411] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0412] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0413] Embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, and The present invention relates to a systemic formulation comprising or consisting of the enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0414] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0415] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0416] Preferred embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 30 wt% of a binder, 0.1 wt% to 35 wt% of a disintegrant, and 0.1 wt% to 10 wt% of a lubricant / flow enhancer.

[0417] Embodiments of the present invention relate to 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a polymer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0418] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, 1 wt The present invention relates to a systemic formulation comprising or consisting of % to 9 wt% of a lubricant / flow enhancer, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0419] Embodiments of the present invention relate to 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a polymer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, 2 wt% to 35 wt% disintegrant, and 1 wt% to 9 wt% lubricant / flow enhancer.

[0420] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0421] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0422] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0423] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, comprising: 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts; 4.5 wt% to 55 wt% of an acidifying agent; 0.1 wt% to 40 wt% of a polymer precipitation inhibitor; 0 wt% to 12 wt% of a binder; and 2 wt% to 35 wt% of a disintegrant. The present invention relates to a systemic formulation comprising or comprising 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0424] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0425] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0426] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0427] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0428] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, The present invention relates to a systemic formulation comprising or consisting of 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0429] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0430] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0431] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0432] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0433] Embodiments of the present invention provide for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, The present invention relates to a systemic formulation comprising or consisting of 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0434] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0435] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0436] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0437] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, and 0 wt% to 12 wt% of a binder.

[0438] Embodiments of the present invention relate to systemic formulations for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer. Regarding.

[0439] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0440] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0441] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0442] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer.

[0443] Embodiments of the present invention include, for use in the prevention and / or treatment of celiac disease, 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, and 1 wt% to 9 wt% of a lubricant / flow enhancer, or a systemic solution. Regarding pharmaceutical preparations.

[0444] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 15 wt% povidone K25, 0.1 wt% to 35 wt% croscarmellose sodium, and 0.1 wt% to 10 wt% talc or silicon dioxide.

[0445] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0446] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0447] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0448] Embodiments of the present invention provide (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% povidone K2 for use in the prevention and / or treatment of celiac disease. 5. The present invention relates to a systemic formulation comprising or consisting of 2 wt% to 35 wt% croscarmellose sodium and 1 wt% to 9 wt% talc or silicon dioxide.

[0449] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide. Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0450] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0451] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0452] Embodiments of the present invention provide (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% POBY for use in the prevention and / or treatment of celiac disease. This invention relates to a systemic formulation comprising or consisting of Don K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0453] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0454] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, 2 wt% to 35 wt% of croscarmellose sodium, and 1 wt% to 9 wt% of talc or silicon dioxide.

[0455] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvation, for use in the prevention and / or treatment of celiac disease. The present invention relates to systemic formulations comprising, or comprising, a substance, a hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0456] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0457] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of hept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0458] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvation, for use in the prevention and / or treatment of celiac disease. The present invention relates to systemic formulations comprising, or comprising, a substance, a hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0459] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% of adipic acid, 0.1 wt% to 40 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0460] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0461] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising, or comprising, a hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0462] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0463] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0464] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% of adipic acid, 3.5 wt% to 30.5 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, and 0 wt% to 12 wt% of povidone K25.

[0465] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0466] Embodiments of the present invention provide a systemic solution for use in the prevention and / or treatment of celiac disease, comprising 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of adipic acid, 2 wt% to 35 wt% of L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% of povidone K25, 2 wt% to 35 wt% of croscarmellose sodium, and 1 wt% to 9 wt% of talc or silicon dioxide. Regarding sexually transmitted drugs.

[0467] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvated, for use in the prevention and / or treatment of celiac disease. The present invention relates to systemic formulations comprising, or comprising, a substance, a hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0468] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvated, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising: a substance, hydrate or pharmaceutically acceptable salt; 4.5 wt% to 55 wt% adipic acid; 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose; 0 wt% to 12 wt% povidone K25; 2 wt% to 35 wt% croscarmellose sodium; and 1 wt% to 9 wt% talc or silicon dioxide.

[0469] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0470] Embodiments of the present invention provide 0.1 wt% to 45 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising, or comprising, a hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0471] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-ethyl for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or consisting of xohepto-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0472] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0473] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising, or comprising, a hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% adipic acid, and 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0474] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a pharmacopoeci, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0475] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a solvate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0476] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 3 wt% to 75 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0477] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, and a solvent for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a dihydrate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 0.1 wt% to 40 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0478] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a pharmacopoeci, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 2 wt% to 35 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0479] Embodiments of the present invention provide 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvated, for use in the prevention and / or treatment of celiac disease. The present invention relates to systemic formulations comprising, or comprising, a substance, a hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, 0 wt% to 12 wt% povidone K25, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

[0480] A very preferred embodiment of the present invention relates to a systemic formulation for use in the prevention and / or treatment of celiac disease, wherein the systemic formulation comprises 2.5 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, Alternatively, the capsule contains an enantiomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30 wt% L-hydroxypropyl cellulose, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide, and preferably 1 wt% to 9 wt% talc.

[0481] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 15 wt% binder, 0.1 wt% to 35 wt% disintegrant, 0.1 wt% to 10 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0482] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0483] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 1 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0484] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 1 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0485] Embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, and The present invention relates to a systemic formulation comprising or consisting of the enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 1 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0486] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0487] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% acidifying agent, 2 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0488] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 3 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0489] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomers, solvates, hydrates or pharmaceutically acceptable salts, 4.5 wt% to 55 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0490] Embodiments of the present invention include (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, and The present invention relates to a systemic formulation comprising or consisting of the enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0491] Embodiments of the present invention relate to a systemic formulation for use in the prevention and / or treatment of celiac disease, comprising or comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate or its enantiomer, solvate, hydrate or pharmaceutically acceptable salt, 4.5 wt% to 55 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0492] Embodiments of the present invention also include 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, and hydrates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a pharmaceutically acceptable salt, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, and 0 wt% to 50 wt% of a diluent / filler / binder.

[0493] Embodiments of the present invention relate to 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, and hydrates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a pharmaceutically acceptable salt, 1 wt% to 75 wt% of an acidifying agent, 2 wt% to 35 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, and 0 wt% to 50 wt% of a diluent / filler / binder.

[0494] Embodiments of the present invention also include 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, and hydrates, for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising a pharmaceutically acceptable salt, 1 wt% to 75 wt% of an acidifying agent, 3.5 wt% to 30 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, and 0 wt% to 50 wt% of a diluent / filler / binder.

[0495] Embodiments of the present invention are for use in the prevention and / or treatment of celiac disease. The present invention relates to a systemic formulation comprising or comprising 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomers, solvates, hydrates, or pharmaceutically acceptable salts, 3 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 12 wt% of a binder, 2 wt% to 35 wt% of a disintegrant, 1 wt% to 9 wt% of a lubricant / flow enhancer, and 0 wt% to 50 wt% of a diluent / filler / binder.

[0496] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, The present invention relates to a systemic formulation comprising or comprising the enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% acidifying agent, 2 wt% to 35 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0497] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, and The present invention relates to a systemic formulation comprising or comprising the enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 3 wt% to 75 wt% acidifying agent, 3.5 wt% to 30 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% diluent / filler / binder.

[0498] Embodiments of the present invention provide 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate for use in the prevention and / or treatment of celiac disease, or The present invention relates to a systemic formulation comprising or comprising the enantiomer, solvate, hydrate or pharmaceutically acceptable salt thereof, 4.5 wt% to 55 wt% acidifying agent, 0.1 wt% to 40 wt% polymer precipitation inhibitor, 0 wt% to 12 wt% binder, 2 wt% to 35 wt% disintegrant, 1 wt% to 9 wt% lubricant / flow enhancer, and 0 wt% to 50 wt% ...

Claims

1. Formula (I) for use in the prevention and / or treatment of celiac disease: 【Chemistry 1】 A systemic preparation comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, or its enantiomer, solvate, hydrate, or pharmaceutically acceptable salt, Here, the systemic preparation is a systemic preparation comprising at least one acidifying agent.

2. The systemic formulation for use according to claim 1, wherein the systemic formulation is an oral formulation, particularly an oral solid formulation.

3. The systemic formulation for use according to claim 1 or claim 2, further comprising at least one binder and / or at least one polymer precipitation inhibitor.

4. The acidifying agent is selected from the group consisting of ascorbic acid, organic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, fumaric acid, maleic acid, malic acid, adipic acid, glutamic acid, etc., and organic tricarboxylic acids, citric acid, and sodium hydrogen citrate, as described in claim 3 for systemic formulation for use.

5. The binder is selected from the group consisting of sugars, sucrose, polysaccharides, xanthan gum, guar gum, carrageenan, starches derived from wheat, corn, rice, and potatoes, pre-aggregated (modified) starches derived from wheat, corn, rice, and potatoes, sodium starch glycolate, natural gums, acacia gum, gelatin, tragacanth, seaweed derivatives, alginic acid, sodium alginate, calcium ammonium alginate, cellulose, cellulose derivatives, hydroxypropylcellulose, L-hydroxypropylcellulose, low-substituted hydroxypropylcellulose, methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, and povidone K25, for a systemic formulation for use according to claim 3.

6. The acidifying agent is adipic acid, and the polymer precipitation inhibitor is polyvinyl alcohol, polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, according to claim 3, a systemic formulation for use.

7. The aforementioned (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxo-hept-2-enoe A systemic formulation for use according to any one of claims 1 to 6, wherein the particle morphology is a particle having a particle size distribution defined by d(0.95) ≤ 25 μm.

8. A systemic formulation for use according to any one of claims 1 to 7, wherein the systemic formulation comprises 0.1 wt% to 80 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, 1 wt% to 75 wt% of an acidifying agent, 0.1 wt% to 40 wt% of a polymer precipitation inhibitor, 0 wt% to 30 wt% of a binder, 0.1 wt% to 35 wt% of a disintegrant, and 0.1 wt% to 10 wt% of a lubricant / flow enhancer.

9. The systemic formulation for use according to any one of claims 1 to 8, wherein the systemic formulation comprises 4.5 wt% to 55 wt% adipic acid.

10. The polymer precipitation inhibitor is polyvinyl alcohol, polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, L-hydroxypropylcellulose, hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and hydroxypropylcellulose, a systemic formulation for use according to claim 8 or 9.

11. The systemic formulation for use according to claim 9, wherein the systemic formulation comprises 4.5 wt% to 55 wt% adipic acid and / or 3.5 wt% to 30.5 wt% L-hydroxypropylcellulose and / or hydroxypropylcellulose, or a combination of L-hydroxypropylcellulose and / or hydroxypropylcellulose.

12. The systemic formulation for use according to any one of claims 1 to 11, comprising 0.1 wt% to 80 wt% (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30 wt% L-hydroxypropylcellulose, 0 wt% to 30 wt% mannitol, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc or silicon dioxide.

13. The systemic formulation for use according to any one of claims 1 to 12, wherein the systemic formulation is a tablet, a coated tablet, a capsule, a powder, or granules.

14. The systemic formulation for use according to claim 13, wherein the systemic formulation is a capsule comprising 2.5 wt% to 30.5 wt% (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate, 4.5 wt% to 55 wt% adipic acid, 3.5 wt% to 30 wt% L-hydroxypropylcellulose, 2 wt% to 35 wt% croscarmellose sodium, and 1 wt% to 9 wt% talc.

15. The systemic formulation comprises 0.1 wt% to 30.5 wt% of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamide)-7-oxohept-2-enoate and 35 wt% to 50 wt% of microcrystals. A systemic formulation for use according to claim 13, comprising a tablet containing hydroxycellulose, 5 wt% to 50 wt% adipic acid, 3.5 wt% to 30 wt% L-hydroxypropylcellulose, 0.01 wt% to 30 wt% mannitol, 3.7 wt% to 15 wt% croscarmellose sodium, and 0.5 wt% to 4.00 wt% silicon dioxide.

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