Oral liquid composition comprising tegoprazan or pharmaceutically acceptable salt thereof

Abstract

An oral liquid composition according to the present invention comprises tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient, a solubilizing agent, and an extra solvent. The present invention has improved the problem of residual foreign body sensation of orally disintegrating tablets conventionally developed for patients with dysphagia. In addition, it is possible to provide a new treatment option for an increasing patient group with gastric acid-related diseases by securing excellent stability of the active ingredient in a solution state, which is a characteristic of an oral liquid dosage form, and presenting a dosage form that ensures uniformity of a preparation.

Description

[0001]

Description of the Invention

[0002]

Title of Invention

[0003] Oral liquid composition comprising tegoprazan or its pharmaceutically acceptable salt

[0004]

Technology Field

[0005] The present invention relates to an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient.

[0006]

Background Skills

[0007] Gastroesophageal reflux disease (GERD) is a condition in which stomach acid refluxes back into the esophagus due to dysfunction of the lower esophageal sphincter, irritating the esophageal mucosa. Recently, the incidence rate has been continuously increasing in modern society, with reports indicating that one in five people suffers from GERD. Furthermore, it has been shown that the risk of developing esophageal cancer in individuals who have suffered from severe GERD for a long period is 44 times higher than that of the general population. While the patient group in their 40s and 50s was previously the largest, the age range of patients with GERD has recently decreased regardless of gender or age, leading to a continuous increase in the number of patients and a rise in prescription volume.

[0008] Proton-pump inhibitors (PPIs) irreversibly bind only to proton pumps activated by hydrogen ion (gastric acid) stimulation, whereas potassium-competitive acid blockers (P-CABs), unlike conventional PPIs, do not require an activation process. Due to this mechanism of action, P-CABs reversibly bind not only to active forms but also to inactive proton pumps within cytoplasmic tubules. Tegoprazan binds to proton pumps reversibly and is more stable in gastric acid than PPIs; because it remains in tubules for a longer period, it can effectively inhibit newly synthesized proton pumps. Furthermore, this mechanism of action allows it to exhibit a faster and more potent gastric acid inhibitory effect compared to conventional PPIs, while also possessing the characteristic of a long duration of action.

[0009] Tegoprazan is the first domestic P-CAB drug for the treatment of gastroesophageal reflux disease, with a standard oral dosage of 50 mg once a day. For patients with mild symptoms, tegoprazan is also prescribed as maintenance therapy at 25 mg once a day, and it is known to provide a powerful gastric acid suppression effect and rapid therapeutic effect.

[0010] K-CAB tablets are manufactured and sold on the market in a film-coated tablet formulation. Generally, film-coated tablet formulations must be taken with water, and since it can be difficult for patients with dysphagia, such as the elderly, to swallow the medication with water, there is a need to improve the method of administration for existing formulations. To this end, K-CAB orally disintegrating tablets are also manufactured and sold on the market.

[0011] Oral disintegrating tablet formulations can be a good alternative for patients with dysphagia, such as the elderly, but some patients may experience a foreign body sensation in the mouth. There is a need for a new formulation that improves upon this by eliminating the foreign body sensation and improving the convenience of administration for various patient groups across different age groups, particularly for children.

[0012] Liquid formulations, whether solutions or suspensions, are prone to precipitation over time, and due to the nature of the formulation where the active ingredient is dispersed within the solution, it is difficult to ensure the homogeneity of the formulation or the quality stability of the active ingredient. Furthermore, depending on the active ingredient, the manufacturing method for liquid formulations can be complex. Tegoprazan has very low water solubility (0.02 mg / mL, pH 6.8), and while its solubility increases under acidic conditions (0.7 mg / mL, pH 3.0), the active ingredient decomposes more rapidly under acidic conditions, making it difficult to ensure stability. Even if solubility is increased using a solubilizer under neutral conditions (pH 7-8), it is difficult to ensure the quality stability of the active ingredient within the solution over time due to the characteristics of the liquid formulation.

[0013] The inventors have made research efforts to develop a novel oral liquid formulation containing tegoprazan that has not been previously invented, which improves upon the disadvantages of commonly known liquid formulations and is easy to manufacture, and thus completed the present invention.

[0014]

Description of the Invention

[0015]

Technical Challenges

[0016] The present invention provides a novel formulation as a preparation having excellent quality stability of an active ingredient in a solution state. Specifically, the present invention provides a composition of an oral liquid formulation containing tegoprazan as an active ingredient, which ensures quality stability and homogeneity.

[0017]

Technical Solution

[0018] The inventors completed the present invention as a result of research aimed at further improving the foreign body sensation remaining in orally disintegrating tablets and providing more diverse treatment options for various patient groups. Accordingly, a composition was developed that prevents the occurrence of precipitation in the solution, ensures homogeneity, and simultaneously ensures quality stability.

[0019] Terms not specifically defined in this specification should be understood to have the meaning commonly used in the technical field to which the present invention belongs. Additionally, unless specifically defined in the context, the singular includes the plural, and the plural includes the singular.

[0020] The present invention relates to an oral liquid composition comprising, as an active ingredient, tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an additional solvent.

[0021] The active ingredient in the present invention, tegoprazan, is also named “(S)-4-(5,7-difluorochroman-4-yloxi)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide ((S)-4-(5,7-di 1uorochroman-4-y 1oxy)-N,N,2-tri 1H-benzo[d]imidazo 1e—6—carboxamide)”.

[0022] The oral liquid composition according to the present invention may be an oral liquid formulation.

[0023] In the present invention, "pharmaceuticalally acceptable salt" means a salt formed with any inorganic acid, organic acid, or base that does not cause severe irritation to a subject to whom a pharmaceutical composition containing an active ingredient is administered, and does not impair the biological activity and physical properties of the active ingredient. As for the salt, salts commonly used in the art, such as acid addition salts formed by pharmaceutically acceptable free acids, may be used, and any salt capable of exhibiting the pharmacological activity of tegoprazan may be used without limitation.

[0024] In one embodiment, the pH of the oral liquid composition according to the present invention may be 5 or higher.

[0025] In one embodiment, the pH of the oral liquid composition according to the present invention may be 5 to 11.

[0026] In one embodiment, the pH of the oral liquid composition according to the present invention may be 5 to 8, 6 to 8, 6 to 7.8, or 6.2 to 7.8. When the pH of the oral liquid composition according to the present invention is 5 or higher and 11 or lower, the active ingredient is not decomposed and no impurities are generated, resulting in excellent storage stability. In one embodiment, the solubilizing agent may include polysorbate, polyethylene glycol, sodium lauryl sulfate, lecithin, polyoxyl 35 castor oil, propylene glycol monocaprylate, glycerin, poloxamer, cyclodextrin, etc. The polysorbate may include polysorbate 20, polysorbate 80, etc. These may each be used individually or in combination of two or more.

[0027] In one embodiment, the solubilizing agent may include one or more selected from polysorbate, polyethylene glycol, sodium lauryl sulfate, and lecithin.

[0028] In one embodiment, the oral liquid composition of the present invention may include a pH adjusting agent. Examples of pH adjusting agents include metaphosphate salts such as dicalcium phosphate, disodium phosphate, dipotassium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, etc., soliphosphate salts such as anhydrous citrate, sodium citrate, sodium citrate hydrate, sodium soliphosphate, etc., pyrophosphate salts such as sodium pyrophosphate, etc., egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, malic acid, etc. Each of these may be used alone or in combination of two or more.

[0029] In one embodiment, the pH adjusting agent may include at least one of dicalcium phosphate, sodium metaphosphate, sodium citrate, sodium citrate hydrate, disodium phosphate, polymix, polyphosphate salt, sodium bicarbonate, pyrophosphate salt, and potassium carbonate. The polymix may include sodium polyphosphate, sodium pyrophosphate, and sodium metaphosphate. In one embodiment, the pH adjusting agent included in the oral liquid composition according to the present invention performs the role of minimizing changes in acidity in the liquid phase and maintaining stability so that the active ingredient is not decomposed.

[0030] In one embodiment, the solvent may be purified water.

[0031] In one embodiment, the oral liquid composition according to the present invention may include a thickening agent.

[0032] In one embodiment, the oral liquid composition according to the present invention may include a polysaccharide thickening agent.

[0033] In one embodiment, the oral liquid composition according to the present invention may include one or more thickening agents selected from gums, alginate salts, and pectin.

[0034] In one embodiment, the oral liquid composition according to the present invention may include one or more selected from non-ionic viscosity enhancers and ionic viscosity enhancers. In one embodiment, the thickening agent may include xanthan gum, iota-carrageenan, pectin, gellan gum, locust bean gum, guar gum, alginate salts such as sodium alginate, etc. These may each be used alone or in combination of two or more.

[0035] In one embodiment, the oral liquid composition according to the present invention may further include one or more additives selected from thickening agents, sweeteners, flavoring agents, preservatives, antioxidants, and coloring agents.

[0036] In one embodiment, the sweetener may include, but is not limited to, sucralose, enzyme-treated ristevia, licorice extract, disodium glycyrrhizinate, neotame, lactitol, D-ribose, mannitol, D-maltitol, maltitol syrup, sodium saccharin, D-sorbitol, D-sorbitol liquid, steviol glycoside, acesulfame potassium, aspartame, erythritol, isomalt, D-xylose, xylitol, tomatine, polyglycol syrup, etc.

[0037] In one embodiment, the flavoring agent is an additive added for a mating effect and can be any ingredient used in the pharmaceutical field, but is not particularly limited. For example, lemon scent can be used as the flavoring agent.

[0038] In the present invention, the antioxidant and the coloring agent can each be selected and used without limitation from among those widely used in the art.

[0039] In one embodiment, the preservative may be one widely used in the art and may include benzoic acid, sodium benzoate, ethyl para-benzoate, butyl para-benzoate, sorbic acid, potassium sorbate, sodium sorbate, chlorobutanol, benzalkonium chloride, benzethonium chloride, phenol, chlorocresol, benzyl alcohol, phenoxyethanol, methyl para-benzoate, propyl para-benzoate, etc.

[0040] In one embodiment, the viscosity of the oral liquid composition according to the present invention may be 190 to 11,000 cP.

[0041] The viscosity in the present invention refers to the viscosity measured at 5 rpm with a spindle S25. The viscosity of the oral liquid composition according to the present invention is 190 to 11,000 cP, which ensures appropriate flowability of the liquid for oral administration, while also providing excellent uniformity of the liquid formulation content.

[0042] In one embodiment, the viscosity of the oral liquid composition according to the present invention may be 190 to 11,000 cP, and the pH may be 5 to 11.

[0043] In one embodiment, the viscosity of the oral liquid composition according to the present invention is 300 to 1,400 cP, and the pH may be 5 to 8 and / or pH 8 to 11.

[0044] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizing agent, a pH adjusting agent, and an excess solvent.

[0045] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizing agent, a pH adjusting agent, a thickening agent, and an excess solvent.

[0046] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizing agent, a pH adjusting agent, a sweetener, a flavoring agent, and an excess solvent.

[0047] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizer, a pH adjuster, a thickening agent, a sweetener, a flavoring agent, and an excess solvent.

[0048] In one embodiment, the oral liquid composition according to the present invention may comprise: tegoprazan or a pharmaceutically acceptable salt thereof; one or more solubilizing agents selected from polysorbate, polyethylene glycol, sodium lauryl sulfate, lecithin, polyoxyl 35 castor oil, propylene glycol monocaprylate, glycerin, poloxamer, and cyclodextrin; one or more pH adjusting agents selected from dicalcium phosphate, disodium phosphate, dipotassium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate hydrate, soliphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid; a thickening agent and an excess solvent.

[0049] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; one or more thickening agents selected from gums, alginate salts and pectins; and an additional solvent.

[0050] In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; one or more pH adjusting agents selected from dicalcium phosphate, disodium phosphate, disodium phosphate, sodium bicarbonate, potassium carbonate, metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, polyphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid; one or more thickening agents selected from gums, alginate salts, and pectin; and an additional solvent. In one embodiment, the oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; a pH adjusting agent; one or more thickening agents selected from gums, alginate salts, and pectin; and an additional solvent.

[0051] In one embodiment, the active ingredient tegoprazan may be included in an amount of 0.01 to 1 part by weight, preferably 0.0625 to 1 part by weight, based on 100 parts by weight of the total weight of the oral liquid composition. For example, tegoprazan may be included in an amount of 0.125 to 0.4 parts by weight based on 100 parts by weight of the total weight of the oral liquid composition, and for example, 0.25 parts by weight.

[0052] In one embodiment, the soluble agent may be included in an amount of 0.02 to 0.4 parts by weight per 100 parts by weight of the total weight of the oral liquid composition, and, for example, may be included in an amount of 0.04 parts by weight.

[0053] In one embodiment, the pH adjusting agent may be included in an amount of 0.01 to 0.25 parts by weight per 100 parts by weight of the total weight.

[0054] In one embodiment, the thickening agent may be contained in an amount of 0.025 to 0.75 parts by weight per 100 parts by weight of the total weight of the composition. For example, xanthan gum may be contained in an amount of 0.125 to 0.375 parts by weight per 100 parts by weight of the total weight of the oral liquid composition.

[0055] In the example, the sweetener may be included in an amount of 0.09 to 0.35 parts by weight per 100 parts by weight of the total weight of the oral liquid composition.

[0056] In one embodiment, the preservative may be included in an amount of 0.001 to 0.04 parts by weight per 100 parts by weight of the total weight.

[0057] In one embodiment, the oral liquid composition according to the present invention can exhibit a dissolution rate of 85% or more in 30 minutes under pH 4.0 dissolution test conditions.

[0058] The oral liquid composition according to the present invention comprises tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient, and P H can be 5 to 11.

[0059] In one embodiment, the oral liquid composition may include one or more pH adjusting agents selected from dicalcium phosphate, disodium phosphate, potassium disodium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, polyphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid.

[0060] In one embodiment, the oral liquid composition may include a solubilizing agent and an additional solvent.

[0061] In one embodiment, the oral liquid composition may include a solubilizing agent, a pH adjusting agent, and an additional solvent.

[0062] In one embodiment, the oral liquid composition may include a solubilizing agent, a pH adjusting agent, a sweetener, a flavoring agent, and an excess solvent.

[0063] The oral liquid composition according to the present invention may comprise tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; and one or more pH adjusting agents selected from calcium monophosphate, sodium disodium phosphate, potassium disodium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, polyphosphate salt, pyrophosphate salt, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid.

[0064] The present invention can produce an oral liquid composition by a manufacturing method comprising the step of mixing tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizing agent, and an excess solvent.

[0065] In one embodiment, the manufacturing method may include the step of mixing tegoprazan or a pharmaceutically acceptable salt thereof, a solubilizing agent, and an excess solvent with at least one of a thickening agent and a pH adjusting agent.

[0066] In one embodiment, the pH of the oral liquid composition obtained according to the above manufacturing method may be 5 to 11.

[0067] In one embodiment, the pH of the oral liquid composition obtained according to the above manufacturing method may be 5 to 8.

[0068] In one embodiment, the viscosity range of the oral liquid composition obtained according to the above manufacturing method, measured at 5 rpm with spindle S25, may be 190 to 11,000 cP.

[0069] The oral liquid composition of the present invention can treat and / or prevent gastric acid-related diseases, e.g., gastroesophageal reflux disease, and has excellent quality stability that is not inferior to that of film-coated tablets even in a solution state.

[0070] The oral liquid composition of the present invention exhibits excellent formulation uniformity because the active ingredient is homogeneously dispersed in the solution.

[0071] The method for preparing a novel formulation of the present invention allows for the formulation of tegoprazan using a simple manufacturing method, making it easy for commercialization and mass production.

[0072] The present invention provides a method for oral administration of a liquid composition comprising: a liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; a solubilizing agent; and an excess solvent; or a liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0073] The present invention provides a liquid composition for oral administration comprising, as an active ingredient, tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an excess solvent, or a liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0074] The present invention provides a liquid composition comprising, as an active ingredient, tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an excess solvent for the manufacture of a drug for oral administration, or a liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0075] The present invention relates to a liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; a solubilizing agent; and an excess solvent, or comprising tegoprazan or a pharmaceutically acceptable salt thereof, P A method for treating or preventing gastric acid-related diseases is provided, comprising administering a liquid composition in which H is 5 to 11.

[0076] The present invention provides an oral liquid composition for treating or preventing gastric acid-related diseases, comprising as an active ingredient tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an excess solvent, or an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0077] The present invention provides an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an excess solvent for the manufacture of a drug for treating or preventing gastric acid-related diseases, or an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient and having a pH of 5 to 11.

[0078] The present invention provides an oral liquid composition for the treatment or prevention of gastric acid-related diseases, comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; a solubilizing agent; and an additional solvent, or comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0079] The present invention provides a method for treating or preventing gastric acid-related diseases, comprising administering an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; a solubilizing agent; and an excess solvent, or an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0080] The present invention provides an oral liquid composition for treating or preventing gastric acid-related diseases, comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient; a solubilizing agent; and an excess solvent, or an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient and having a pH of 5 to 11.

[0081] The present invention provides an oral liquid composition comprising, as an active ingredient, tegoprazan or a pharmaceutically acceptable salt thereof; a solubilizing agent; and an excess solvent for the manufacture of a drug for treating or preventing gastric acid-related diseases, or an oral liquid composition comprising tegoprazan or a pharmaceutically acceptable salt thereof and having a pH of 5 to 11.

[0082] In addition, the present invention includes the following items (1) to (21) in relation to an oral liquid composition, method and use.

[0083] (1) An oral liquid composition according to the present invention comprises tegoprazan or its pharmaceutically acceptable salt as an active ingredient; a solubilizing agent; and an additional solvent.

[0084] (2) In the above (1), the oral liquid composition may have a pH of about 5 or higher.

[0085] (3) In the above (1) or (2), the oral liquid composition may have a pH of about 5 to about 11. (4) In any one of the above (1) to (3), the oral liquid composition may have a pH of about 5 to about 8.

[0086] (5) In any one of (1) to (4) above, the solubilizing agent may include at least one selected from polysorbate, polyethylene glycol, sodium lauryl sulfate, lecithin, polyoxyl 35 castor oil, propylene glycol monocaprolactate, glycerin, poloxamer, and cyclodextrin.

[0087] (6) In any one of (1) to (5) above, the oral liquid composition may include a pH adjusting agent.

[0088] (7) In any one of (1) to (6) above, the oral liquid composition may include one or more pH adjusting agents selected from dicalcium phosphate, disodium phosphate, potassium disodium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, soliphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid.

[0089] (8) In any one of (1) to (7) above, the oral liquid composition may include a thickening agent.

[0090] (9) In any one of (1) to (8) above, the oral liquid composition may include one or more thickening agents selected from gums, alginate salts and pectin.

[0091] (10) In any one of (1) to (9) above, the oral liquid composition may include at least one thickening agent selected from xanthan gum, iota-carrageenan, pectin, locust bean gum, guar gum, gellan gum, and sodium alginate.

[0092] (11) In any one of (1) to (10) above, the oral liquid composition may include one or more additives selected from thickeners, sweeteners, flavoring agents, preservatives, antioxidants and coloring agents.

[0093] (12) In any one of (1) to (11) above, the oral liquid composition may have a viscosity of about 190 cP to about 11,000 cP when measured at about 5 rpm with spindle S25.

[0094] (13) In any one of (1) to (12) above, the oral liquid composition may contain the active ingredient in an amount of about 0.01 to about 1 part by weight per 100 parts by weight of the total weight of the composition.

[0095] (14) In any one of (1) to (13) above, the oral liquid composition may contain about 0.02 to about 0.4 parts by weight of a soluble agent per 100 parts by weight of the total weight of the composition.

[0096] (15) In any one of (1) to (14) above, the oral liquid composition may include about 0.01 to about 0.25 parts by weight of a pH adjusting agent per 100 parts by weight of the total weight of the composition.

[0097] (16) In any one of (1) to (15) above, the oral liquid composition may contain about 0.025 parts by weight to about 0.75 parts by weight of a thickening agent per 100 parts by weight of the total weight of the composition.

[0098] (17) An oral liquid composition according to the present invention comprises tegoprazan or a pharmaceutically acceptable salt thereof as an active ingredient, and P H can be about 5 to about 11.

[0099] (18) In the above (17), the oral liquid composition may contain one or more pH adjusting agents selected from dicalcium phosphate, disodium phosphate, potassium disodium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citric acid, sodium citrate, sodium citrate hydrate, soliphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate and malic acid.

[0100] (19) In addition, the present invention provides a method for oral administration of a liquid composition comprising administering a composition according to any one of (1) to (18) orally.

[0101] (20) In addition, the present invention provides a use for administering another composition orally to any one of (1) to (18).

[0102] (21) In addition, the present invention provides a use for manufacturing a drug for orally administering a composition according to any one of (1) to (18).

[0103]

Effects of the Invention

[0104] The oral liquid composition according to the present invention has excellent bioavailability as the pharmacologically active ingredient exists in a solution state, thereby maintaining a rapid therapeutic effect without a decrease in dissolution over time; it has excellent taste and aroma, making it easy to take; and it allows for convenient dosage adjustment according to the patient's condition or body weight, which can improve patient compliance. Furthermore, the oral liquid composition according to the present invention ensures quality stability in the solution state and homogeneity of the formulation, and can provide new dosage options for patient groups of various age groups. Moreover, the oral liquid composition according to the present invention prevents recrystallization, precipitation, precipitation occurrence, and the generation of related substances even during long-term storage, and since stability is improved and the homogeneity of pharmacological efficacy is enhanced, it can be usefully utilized for the treatment and / or prevention of gastric acid-related diseases.

[0105]

Brief Description of the Drawing

[0106] Figure 1 shows the dissolution results of the embodiments according to the present invention compared with commercially available K-Cap tablets under pH 4.0 conditions.

[0107]

Form for carrying out the invention

[0108] The structure and effects of the present invention will be explained in more detail below through comparative examples and embodiments. These comparative examples and embodiments are solely for the purpose of illustrating the present invention, and the scope of the present invention is not limited by them.

[0109] <Test Method>

[0110] 1. Check characteristics, such as whether precipitation has occurred

[0111] The occurrence of precipitation in the samples prepared for each composition was checked visually. 2. Formulation Uniformity Test and Evaluation

[0112] A formulation uniformity test was conducted according to the following test methods and evaluation methods.

[0113] Dilution solution: Acetonitrile • Water mixture (1:1)

[0114] Standard solution: A solution prepared by accurately weighing 50 mg of Tegoprazan standard, placing it in a 100 mL volumetric flask, adding 50 mL of diluent to dissolve it, and adjusting the volume to exactly 100 mL with the diluent. Test solution: A solution prepared by taking one packet of this medicine, placing it in a 100 mL volumetric flask, adding 50 mL of diluent to completely disintegrate the tablet, sonicating for about 20 minutes to completely extract Tegoprazan, adjusting the volume to exactly 100 mL with the diluent, and filtering it through a filter. After analysis using HPLC, the relative standard deviation (RSD) for the samples was calculated, and if it was 5.0% or less, it was determined to be homogeneous.

[0115] 3. Viscosity measurement

[0116] The viscosity of each sample was measured according to the rotational viscometer method, Method 2 of the viscosity measurement methods in the general test methods of the Korean Pharmacopoeia. An S25 spindle was used, and the speed was set to 5 rpm.

[0117] 4. Quality Stability (Accelerated) Testing

[0118] The manufactured samples were sealed in aluminum pouches and left for 3 days, 1 week, or 1 month at 40°C to 2°C and 75% RH to 5%, and then analyzed using HPLC to confirm the trend of occurrence of impurities as an area percentage.

[0119] Example: Preparation of Samples- 1

[0120] Samples were prepared having the components and content according to Tables 1 to 4 below, per unit pouch with a total weight of 20 g. The unit of total weight is g, and the unit of weight for each component is mg. Hereinafter, in the composition, qs is an abbreviation for "quantity sufficient," meaning "a sufficient amount of solvent (purified water) is added so that the total weight becomes 20,000 mg (20 g)."

[0121] In each composition, (1) tegoprazan and a solubilizing agent were added to a solvent to dissolve and disperse them, (2) a thickening agent was added to the solvent by stirring and dispersing it, and then heated to dissolve it, and (3) the above (1) and (2) were mixed. In addition, (4) a pH adjusting agent was dissolved in the solvent and mixed with the solution of (3) to adjust the pH, and (5) a sweetener and a flavoring agent were added to the solution of (4) and then homogeneously mixed using a mechanical stirrer. (6) purified water was added to the above (5) to make a total of 20 g, and a sample was prepared in units of 20 g / pack. The amount of purified water used in each of (1) to (4) can be selected as an appropriate amount capable of dissolving each component.

[0122] [Table 1]

[0123] Classification Composition Composition Composition Composition Composition Composition 2 4 6 7 Main Ingredient Tegoprazan 50 50 50 50 50 50 50 Thickening Agent Xanthan Gum 50 50 50 50 50 50 50 Soluble Agent Polysorbate 80 8 8 8 8 8 8 8 Calcium Monophosphate 50

[0124] Sodium metaphosphate 50

[0125] pH 50 sodium citrate

[0126] Regulator Potassium diphosphate 50

[0127] 50 sodium diphosphate

[0128] Polymix 50 Polyphosphate 50 Sweetener Sucralose 30 30 30 30 30 30 30

[0129]

[0130] Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 5 Flavoring Agent Lemon Scent 5 5 5 5 5 5 5 Solvent Purified Water qs qs qs qs qs qs qs qs

[0131]

[0132] Total weight (g) 20 20 20 20 20 20 20

[0133] [Table 2]

[0134] Classification Composition Composition Composition Composition Composition Composition 8 10 11 12 13 14 Main Ingredient Tegoprazan 50 50 50 50 50 50 50 Thickening Agent Xanthan Gum 50 50 50 50 50 50 50 Solubilizing Agent Polysorbate 80 8 8 8 8 8 8 8 Sodium Bicarbonate 50

[0135] Pyrophosphate 50

[0136] pH Potassium Carbonate 50

[0137] Regulator Tartaric Acid 50

[0138] Anhydrous acid 50 DL-Malic acid 50 Succinic acid 50 Sweetener Sucralose 30 30 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 5 Flavoring agent Lemon scent 5 5 5 5 5 5 5 Solvent Purified water qs qs qs qs qs qs qs qs

[0139]

[0140] Total weight (g) 20 20 20 20 20 20 20

[0141] [Table 3]

[0142] Classification Composition Composition Composition Composition Composition Composition 15 16 17 18 19 20 21 Main Ingredient Tegoprazan 50 50 50 50 50 50 50 Thickening Agent Xanthan Gum 50 50 50 50 50 50 50 Solubilizing Agent Polysorbate 80 8 8 8 8 8 8 8 Calcium Monophosphate 8.62

[0143] Sodium citrate 5.90

[0144] pH Sodium Citrate Hydrate 8.40

[0145] Regulator Potassium diphosphate 0.25

[0146] Sodium diphosphate 3.75 Sodium bicarbonate 0.24 Potassium carbonate 1.20 Sweetener Sucralose 30 30 30 30 30 30 30 Sweetener Enzymatically treated Stevia 5 5 5 5 5 5 5 Flavoring Agent Lemon scent 5 5 5 5 5 5 5 Solvent Purified water qs qs qs qs qs qs qs qs

[0147]

[0148] Total weight (g) 20 20 20 20 20 20 20

[0149] [Table 4] Classification Composition Composition Composition Composition Composition Composition 22 23 24 25 26 27 28 Main Component Tegoprazan 50 50 50 50 50 50 50 Thickening Agent Tan Gum 50 50 50 50 50 50 50 Solubilizing Agent Polysorbate 80 8 8 8 8 8 8 8 Sodium Metaphosphate 0.55

[0150] 2.57 tartaric acid

[0151] pH Anhydrous Calculation 0.07 0.07 4.11

[0152] Sodium citrate 0.09

[0153] Sodium citrate hydrate 0.21

[0154] DL-Malic Acid 3.25 Succinic Acid 1.35 Sweetener Sucralose 30 30 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 5 Flavoring Agent Lemon Scent 5 5 5 5 5 5 5 Solvent Purified Water q. s q. s q. s q. s q. s q. s q. s

[0155]

[0156] Total weight (g) 20 20 20 20 20 20 20

[0157] Check for precipitation

[0158] For each of the samples prepared according to Tables 1 to 4, the occurrence of precipitation was visually checked after leaving them at room temperature for one day. As a result, it was confirmed that no precipitation occurred in any of the samples containing the soluble fire agent, and they remained stable.

[0159] Stability evaluation

[0160] The pH of the samples prepared according to Tables 1 to 4 was measured, and stability was evaluated under accelerated conditions. The results are shown in Tables 5 and 6 below.

[0161] [Table 5]

[0162] Category Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Initial Flexible Material 0.1 0.1 0.1 0.1 0.1 Accelerated 3-Day Generation Ratio (%) 0.2 0.1 0.1 0.1 0.1 Initial pH 5.0 6.6 7.2 8.0 8.4 Accelerated 3-Day pH 4.9 6.5 7.0 7.5 7.8 Category Composition 6 Composition 7 Composition 8 Composition 9 Composition 10 Initial Flexible Material 0.1 0.1 0.1 0.1 0.1 Accelerated 3-Day Generation Ratio (%) 0.1 0.1 0.1 0.1 0.2 Initial pH 8.7 9.0 9.0 9.3 10.7 Accelerated 3-Day pH 7.7 8.0 8.4 8.7 10.3 Category Composition 11 Composition 12 Composition 13 Composition 14

[0163] Initial flexible material 0.3 0.3 0.2 0.1

[0164] Accelerated 3-Day Generation Rate (%) 10.2 8.4 7.7 3.7

[0165]

[0166] Initial pH 3.0 3.3 3.2 3.6 Accelerated 3 days pH 2.9 3.2 3.2 3.6

[0167] [Table 6]

[0168] Category Composition 15 Composition 16 Composition 17 Composition 18 Composition 19 Initial Flexible Material 0.1 0.1 0.1 0.1 0.1 Accelerated Week 1 Generation Ratio (%) 0.2 0.1 0.1 0.1 0.1 Initial pH 5.6 7.1 7.2 6.6 7.8 Accelerated Week 1 pH 5.4 6.5 6.8 6.1 6.3 Category Composition 20 Composition 21 Composition 22 Composition 23 Composition 24 Initial Flexible Material 0.1 0.1 0.1 0.1 0.1 Accelerated Week 1 Generation Ratio (%) 0.1 0.1 0.1 0.1 0.1 Initial pH 7.5 7.2 6.4 6.0 6.2 Accelerated Week 1 pH 6.6 6.1 5.9 6.0 5.9 Category Composition 25 Composition 26 Creation 27 Creation 28

[0169] Initial flexible material 0.1 0.1 0.1 0.1

[0170] Accelerated Week 1 Generation Rate (%) 1.5 1.7 1.3 0.4

[0171] Initial pH 4.5 4.5 4.4 4.9

[0172]

[0173] Acceleration 1 week pH 4.4 4.5 4.5 5.3

[0174] Referring to Tables 5 and 6, it can be seen that the pH is maintained stably without the formation of flexible substances at pH 5 to 11.

[0175] Example: Preparation of Samples- 2

[0176] Samples having the ingredients and content according to Table 7 below were prepared per unit pouch with a total weight of 20 g. The unit of total weight is g, and the unit of weight for each ingredient is mg. The preparation method for each sample is the same as described above.

[0177] [Table 7]

[0178] Classification Composition 29 Composition 30 Composition 31 Composition 32 Composition 33 Comparative Composition Main Ingredient Tegoprazan 50 50 50 50 50 50 Thickening Agent Xanthan Gum 25 25 25 25 25 25 Polysorbate 80 8 - Polysorbate 20 8 - Solubilizing Agent Polyethylene Glycol 400 8 - Sodium Lauryl Sulfate 8 - Lecithin 8 - pH Adjuster Sodium Citrate Hydrate 50 50 50 50 50 50 Sweetener Sucralose 30 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 Flavoring Agent Lemon Flavor 5 5 5 5 5 5 Solvent Purified Water qs qs qs qs qs qs qs

[0179]

[0180] Total weight (g) 20 20 20 20 20 20 Evaluation of content uniformity of the liquid formulation

[0181] The formulation uniformity characteristics were evaluated for the samples prepared according to Table 7. The results are shown in Table 8 below.

[0182] [Table 8]

[0183] Classification Composition 29 Composition 30 Composition 31 Composition 32 Composition 33 Comparative Composition Formulation Uniformity 0.4 1.5 1.5 1.6 2.6 6.4

[0184]

[0185] RSD (%)

[0186] Referring to Table 8, it can be seen that the samples according to the embodiments of the present invention have excellent content uniformity. On the other hand, it can be seen that the comparative composition not containing a solubilizing agent has significantly poor content uniformity.

[0187] Example: Preparation of Samples- 3

[0188] Samples having the ingredients and content according to Table 9 below were prepared per unit pouch with a total weight of 20 g. The unit of total weight is g, and the unit of weight for each ingredient is mg. The preparation method for each sample is the same as described above.

[0189] [Table 9]

[0190] division

[0191] Main ingredient Tego Pra Zan 50 50 50 50 50 50 50 50 50 50 Xanthan Gum 50

[0192] Iota Caraghi Nan 50 36

[0193] 100% Pectin

[0194] Thickening agent Gellan gum 50 24

[0195] Sodium alginate 50 60 Locust bean gum 60

[0196] Guar gum 36 Solubilizing agent Polysorbate 80 8 8 8 8 8 8 8 8 8 8 pH regulator Sodium citrate hydrate 50 50 50 50 50 50 50 50 50 50 Sweetener Sucralose 30 30 30 30 30 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 5 5 5 Flavoring agent Lemon scent 5 5 5 5 5 5 5 5 5 Solvent Purified water q. s q. s s s s s s s s s s s s s s s s s s s s s s s s s s s s

[0197]

[0198] Total weight (g) / pack 20 20 20 20 20 20 20 20 20 20

[0199] For each sample prepared according to Table 9 regarding the occurrence of precipitation, the occurrence of precipitation was visually checked after leaving them at room temperature for one day. As a result, it was confirmed that no precipitation occurred in any of them and they remained stable.

[0200] pH and viscosity measurement

[0201] pH and viscosity were measured for the samples prepared according to Table 9. The results are shown in Table 10 below.

[0202] [Table 10]

[0203] Category Composition 34 Composition 38 Composition 39 Composition 40 Composition 41 Composition 42 Composition 43 pH 8.1 7.7 7.5 7.6 6.3 7.6 7.8

[0204]

[0205] Viscosity (cP) 1536 192 192 288 288 288 384

[0206] Evaluation of liquid content uniformity

[0207] Content uniformity evaluation was performed on samples having the composition of Table 9, and the results are shown in Table 11 below.

[0208] [Table 11]

[0209] Classification Composition 34 Composition 35 Composition 36 Composition 37 Composition 38 Formulation Uniformity

[0210] RSD (%) 1.5 4.8 1 2.5 3.5 Classification Composition 39 Composition 40 Composition 41 Composition 42 Composition 43 Formulation Uniformity 1.7 3.1 3.6 4.4 1.7

[0211]

[0212] RSD (%)

[0213] Referring to Table 11, it is confirmed that for each of compositions 34 to 43 according to the embodiments of the present invention, the content uniformity in the liquid preparation is excellent.

[0214] Example: Preparation of Samples- 4

[0215] Samples were prepared having the components and content according to Table 12 below, per unit pouch with a total weight of 20 g. The unit of total weight is g, and the unit of weight for each component is mg. The preparation method for each sample is the same as described above.

[0216] [Table 12]

[0217] Classification Composition 44 Composition 45 Composition 46 Composition 47 Composition 48 Composition 49 Composition 50 Main Component Tegoprazan 50 50 50 50 50 50 50

[0218]

[0219] Thickening agent Xanthan gum 5 10 25 50 75 100 150 Solubilizer Polysorbate 80 8 8 8 8 8 8 8 pH regulator Sodium citrate hydrate 50 50 50 50 50 50 50 Sweetener Sucralose 30 30 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 5 5 Flavoring agent Lemon scent 5 5 5 5 5 5 5 Solvent Purified water q. s q. s q. s q. s q. s q. s q. s

[0220]

[0221] Total weight (g) 20 20 20 20 20 20 20

[0222] Check for precipitation

[0223] The samples prepared according to Table 12 were left at room temperature for one day, and the occurrence of precipitation was visually checked. As a result, it was confirmed that no precipitation occurred in any of them and they remained stable.

[0224] Verification of viscosity characteristics and evaluation of liquid content uniformity

[0225] The results of the viscosity and content uniformity evaluations performed on samples prepared according to Table 12 are shown in Table 13 below.

[0226] [Table 13]

[0227] Classification Composition 44 Composition 45 Composition 46 Composition 47 Composition 48 Composition 49 Composition 50 1st Measurement Viscosity (cP) 192 1152 1440 2304 3456 5088 10540 2nd Measurement Viscosity (cP) 192 1248 1440 2400 3456 5184 10650 Formulation Uniformity 1.7 2.8 2.5 0.3 2.7 2.4 1.1

[0228]

[0229] RSD (%)

[0230] Referring to Table 13, when liquid formulations are prepared using xanthan gum in various amounts, it can be confirmed that the uniformity of the formulation content is excellent at 190 to 11,000 cP.

[0231] Example: Preparation of Sample- 4

[0232] Samples were prepared for each unit pouch with a total weight of 20 g, having the components and content according to Table 14 below. The unit of total weight is g, and the unit of weight for each component is mg. The method of preparing the samples is the same as described above.

[0233] [Table 14]

[0234] Classification Composition 51

[0235] Main ingredient: Tego Prazan 50

[0236] Increasing agent Xanthan gum 50

[0237] Available fire-resistant polysorbate 80 8

[0238]

[0239] Sweetener Sucralose 30 Sweetener Enzyme-treated Stevia 5

[0240] Flavoring agent: Lemon scent 5

[0241] Solvent purification water qs

[0242]

[0243] Total weight (g) 20

[0244] It was confirmed that no precipitation occurred with respect to Composition 51 according to an embodiment of the present invention.

[0245]

[0246] Samples were prepared having the components and content according to Table 15 below, per unit pouch with a total weight of 20 g. The unit of total weight is g, and the unit of weight for each component is mg. The method of preparing the samples is the same as described above.

[0247] [Table 15]

[0248] Classification Composition 52 Composition 53 Composition 54 Composition 55 Composition 56 Main Ingredient Tegoprazan 50 50 50 50 50 Thickening Agent Xanthan Gum 25 25 75 75 50 Solubilizing Agent Polysorbate 80 8 8 8 8 8 Sweetener Sucralose 30 30 30 30 30 Sweetener Enzyme-treated Stevia 5 5 5 5 5 pH Adjuster Sodium Citrate Hydrate 2 8 2 8 5 Flavoring Agent Lemon Scent 5 5 5 5 5 Solvent Purified Water qs qs qs qs qs qs

[0249]

[0250] Total weight (g) 20 20 20 20 20

[0251] Check for precipitation and pH characteristics

[0252] The pH and occurrence of supernatant precipitation of the samples were checked according to Table 15. The results are shown in Table 16 below.

[0253] [Table 16]

[0254] Classification Composition 52 Composition 53 Composition 54 Composition 55 Composition 56 Precipitation occurrence

[0255] (Room temperature 30 days) Not developed Not developed Not developed Not developed Not developed Initial pH 6.93 7.52 7.18 7.66 7.32

[0256]

[0257] After 30 days pH 6.63 7.48 6.82 7.42 7.20

[0258] Referring to Table 16, it was confirmed that no precipitation occurred when the vials of compositions 52 to 56 according to the embodiments of the present invention were stored in an open state at room temperature for 30 days. In addition, it was confirmed that the pH remained unchanged over time.

[0259] Evaluation of liquid content uniformity

[0260] The results of the content uniformity evaluation performed on the samples according to Table 15 are shown in Table 17 below.

[0261] [Table 17]

[0262] Classification Composition 52 Composition 53 Composition 54 Composition 55 Composition 56 Formulation Uniformity 1.4 2 1.5 0.9

[0263]

[0264] RSD (%) 1.1

[0265] Referring to Table 17, it was confirmed that compositions 52 to 56 according to the embodiments of the present invention are all formulations having excellent content uniformity.

[0266] Stability evaluation

[0267] The results of the stability tests of the samples according to Table 15 are shown in Table 18 below.

[0268] [Table 18]

[0269] Classification Composition 52 Composition 53 Composition 54 Composition 55 Composition 56 Precipitation Occurrence None Occurrence None Occurrence None Occurrence None Occurrence Initial Flexible Material

[0270] Generation Rate (%) 0 0 0.05 0.06 0.05 Accelerated 1 Month Flexible Material

[0271] Production Rate (%) 0 0.05 0.1 0.17 0.1 Accelerated 2 Months Flexible Material

[0272] Production Rate (%) 0.25 0.12 0.17 0.09 0.12 Initial pH 6.9 7.5 7.2 7.7 7.3 Accelerated 1 Month pH 6.2 6.5 6.8 7.0 6.9

[0273]

[0274] Acceleration 2 months pH 6.3 6.1 6.8 6.4 6.5

[0275] Referring to Table 18, it was confirmed that in all samples according to the embodiments of the present invention, the derivative of the active ingredient tegoprazan did not change significantly compared to the initial state over time under accelerated 1-month and 2-month conditions, and the stability of the formulation was confirmed to be excellent.

[0276] Evaluation of dissolution characteristics

[0277] For the samples prepared according to Table 15, an in vitro comparative dissolution test with the commercially available K-Cap tablet 50 mg was performed under the following test conditions. The results are shown in Figure 1.

[0278] <Dragon Release Trial Conditions>

[0279] 1) Dissolution method: United States Pharmacopoeia (USP) Dissolution Test Method II (Paddle Method)

[0280] 2) Dissolution Solution: Korean Pharmacopoeia Dissolution Test Solution No. 2 (pH 4.0)

[0281] 3) Amount of eluent: 900 mL

[0282] 4) Dissolving agent temperature: 37°C 5°C

[0283] 5) Paddle speed: 75 rpm

[0284] After the start of the test, elution test samples were collected at 5, 10, 15, and 30 minutes, filtered, and analyzed by HPLC.

[0285] Referring to Figure 1, it was confirmed that the samples prepared according to Table 15 exhibited an elution rate of 85% or more in 30 minutes under pH 4.0 elution test conditions.

Claims

【Scope of Claim】 【Claim 11 Tegoprazan or its pharmaceutically acceptable salt as an active ingredient; a solubilizing agent; and containing extra solvent Oral liquid composition.

2. In claim 1, an oral liquid composition having a pH of 5 or higher.

3. An oral liquid composition according to claim 1 or 2, wherein the pH is 5 to 11.

4. An oral liquid composition having a pH of 5 to 8 in any one of claims 1 to 3.

5. In claim 1, the above-mentioned soluble fire is Comprising one or more selected from polysorbate, polyethylene glycol, sodium lauryl sulfate, lecithin, polyoxyl 35 castor oil, propylene glycol monocaprylate, glycerin, poloxamer, and cyclodextrin, Oral liquid composition.

6. In claim 1, the above composition is an oral liquid composition comprising a pH adjusting agent.

7. In claim 1, the above composition is Comprising one or more pH adjusters selected from dicalcium phosphate, disodium phosphate, dipotassium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, soliphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid, Oral liquid composition.

8. In claim 1, the above composition is An oral liquid composition containing a thickening agent. 【Claim this In claim 1, the above composition is An oral liquid composition comprising one or more thickening agents selected from gums, alginate salts, and pectin.

10. In claim 1, the above composition is An oral liquid composition comprising at least one thickening agent selected from xanthan gum, iota-carrageenan, pectin, locust bean gum, guar gum, gellan gum, and sodium alginate.

11. In claim 1, the above composition is Comprising one or more additives selected from thickeners, sweeteners, flavorings, preservatives, antioxidants, and colorings, Oral liquid composition.

12. An oral liquid composition according to claim 1, wherein the viscosity is 190 cP to 11,000 cP when measured at 5 rpm with spindle S25.

13. In claim 1, the active ingredient is Included in an amount of 0.01 to 1 weight part per 100 weight parts of the total weight of the composition, Oral liquid composition.

14. In claim 1, the above-mentioned soluble fire is An oral liquid composition contained in an amount of 0.02 to 0.4 parts by weight per 100 parts by weight of the total weight of the composition.

15. In claim 1, the above composition is A composition comprising 0.01 to 0.25 parts by weight of a pH adjusting agent per 100 parts by weight of the total weight of the composition Oral liquid composition.

16. In claim 1, the above composition is A composition comprising 0.025 to 0.75 parts by weight of a thickening agent per 100 parts by weight of the total weight of the composition Oral liquid composition.

17. Containing tegoprazan or its pharmaceutically acceptable salt as an active ingredient, pH 5 to 11, Oral liquid composition.

18. In Paragraph 17, Comprising one or more pH adjusters selected from dicalcium phosphate, disodium phosphate, dipotassium phosphate, sodium bicarbonate, potassium carbonate, sodium metaphosphate, anhydrous citrate, sodium citrate, sodium citrate hydrate, soliphosphate, pyrophosphate, egg white powder, calcium carbonate, sodium carbonate, calcium sulfate, and malic acid, Oral liquid composition. 【Claim 1 is Comprising oral administration of the liquid composition according to claim 1 Method of oral administration of a liquid composition.

20. Use for oral administration of the liquid composition according to Article 1.

21. Use for manufacturing a pharmaceutical product for oral administration of a liquid composition according to Claim 1.

22. A method for oral administration of a liquid composition comprising administering the liquid composition according to claim 17 orally.

23. Use for oral administration of a liquid composition according to Clause 17. 【claim Paragraph 24 Use for the manufacture of a drug for oral administration of a liquid composition according to Clause 17.

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