Self-emulsifying composition and self-emulsifying drug delivery system.

Description

41 Self-emulsifying composition and self-emulsifying drug delivery system. Technical Field

[001] This disclosure relates to a self-emulsifying composition containing a sulfonamide derivative and a self-emulsifying drug delivery system. Fundamentals

[002] It is known that compounds with molecular weights of 500 or more generally exhibit low water solubility and low membrane permeability at the time of oral administration (Donovan, MD et al. (1990) Absorption of polyethylene glycols 600 through 2000: The molecular weight dependence of gastrointestinal and nasal absorption. Pharm. Res. 7, 863-868). In the case of preparing a pharmaceutical product containing such a compound, there is a problem that absorbability decreases due to low solubility or membrane permeability in the gastrointestinal tract after oral administration. For this reason, to improve the absorption of a compound, various pharmaceutical measures have been taken. For example, a self-emulsifying drug delivery system composed of an oil, a surfactant and the like (hereinafter referred to as “SEDDS”) is also one of these measures.SEDDS is a formulation prepared by uniformly mixing and dissolving or dispersing an active ingredient in a water-free state. When SEDDS is administered orally, it is dispersed or dissolved in an aqueous content in the gastrointestinal tract to form an emulsion, thus improving the solubility, membrane permeability, and absorbability of the contained compound.

[003] It is reported that the possibility of applying SEDDS has been studied in studies to improve membrane permeability or absorbability, for medium molecular weight compounds with low Petition 870250090533, dated 03 / 10 / 2025, p. 13 / 60 2 / 41 membrane permeability in Japanese Patent Application Publication No. 2021-169476, for tetrahydropyrazolopyrimidinone compounds in the Published Japanese Translation of International PCT Application No. 2022-540780 and for ω3 polyunsaturated fatty acids in Japanese Patent Application Publication No. 2021-107433.

[004] It has been reported that a sulfonamide derivative represented by the following formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof has an inhibitory action on integrin a4 and is useful as a pharmaceutical agent for use in the treatment or prevention of inflammatory bowel diseases and similar conditions (International Publication No. WO2017 / 135472). However, findings regarding the membrane permeability or absorbability of this compound, which has a molecular weight of 500 or more, were not satisfactory. Summary of the Invention Problems to be solved by the invention

[005] Even compounds with molecular weights of 500 or more have various physical properties, such as solubility and membrane permeability, and it is unclear whether the use of SEDDS can improve the absorption capacity of a compound. Furthermore, it is unclear which component can be combined with a compound to prepare SEDDS that can Petition 870250090533, dated 03 / 10 / 2025, p. 14 / 60 / 41 to improve membrane solubility and permeability.

[006] With regard to the sulfonamide derivative represented by the above formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof, the present inventors’ studies have revealed that there is room to improve the amount of blood exposure in the case of simple oral administration of a powder or suspension of this compound. That is, a further improvement in membrane permeability and absorption capacity was desired.

[007] The present disclosure was discovered by the present inventors who have seriously studied such situations, and one of the objectives of the present disclosure is to provide a pharmaceutical composition comprising a sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof, and having improved absorbability at the time of oral administration.

[008] The present inventors conducted several studies to solve the above problems and found that the absorbability of the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof or an active metabolite thereof can be improved by preparing a self-emulsifying composition comprising: the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof or an active metabolite thereof; and at least two solubilizers, thus completing the invention.

[009] Non-limiting aspects of this disclosure provide the following technical insights.

[0010] [1] A self-emulsifying composition comprising: a sulfonamide derivative represented by the following formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof; and at least two solubilizers Petition 870250090533, dated 03 / 10 / 2025, page 15 / 60 4 / 41

[0011] [2] The self-emulsifying composition according to [1], wherein the at least two solubilizers comprise at least one surfactant and at least one auxiliary surfactant.

[0012] [3] The self-emulsifying composition according to [1], wherein the solubilizers comprise at least two selected from a cyclodextrin or a derivative thereof, bile acid or a derivative thereof, a fatty alcohol, a fatty acid or derivatives thereof and a tocol derivative.

[0013] [4] The self-emulsifying composition according to [2], wherein the surfactant comprises at least one selected from the group consisting of polyglyceryl-2 dioleate, polyglyceryl-3 dioleate, polyglyceryl-10 trioleate, propylene glycol monolaurate, propylene glycol monocaprylate, glyceryl monocaprylate, glyceryl monolaurate, glyceryl dilaurate and glyceryl monolinoleate.

[0014] [5] The self-emulsifying composition according to [2], wherein the auxiliary surfactant comprises at least one selected from the group consisting of polyoxyl 40 castor oil, polyoxyl 35 castor oil, PEG-25 trioleate, PEG-60 maize glycerides, PEG-60 almond oil, PEG-40 palm kernel oil, PEG-50 castor oil, PEG-50 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-8 caprylic / capric glycerides, polyoxyl-32 lauroyl glycerides, polyoxyl-6 linoleyl glycerides, polyoxyl-6 oleoyl glycerides, polyoxyl-32 stearoyl glycerides, glycerides Petition 870250090533, dated 03 / 10 / 2025, p. 16 / 60 / 41 caprylic / capric PEG-6, polyglyceryl-10 monooleate, polyglyceryl-10 laurate, polyglyceryl-15 hydroxystearate, PEG-400 α-tocopherol succinate, PEG-1000 α-tocopherol succinate, PEG-1000 dl-α-tocopherol succinate and PEG-1000 da-tocopherol succinate.

[0015] [6] The self-emulsifying composition according to any of [2], [4] and [5], wherein the content of the surfactant is 0.1 times or more in relation to the % by mass of the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof, and the content of the auxiliary surfactant is 10 times or less in relation to the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof.

[0016] [7] The self-emulsifying composition according to any one of [2] and [4] to [6], wherein the ratio of surfactant to auxiliary surfactant is from 1:1 to 8:1.

[0017] [8] The self-emulsifying composition according to any one of [2] and [4] to [7], wherein the surfactant comprises propylene glycol monocaprylate.

[0018] [9] The self-emulsifying composition according to any one of [2] and [4] to [8], wherein the auxiliary surfactant comprises polyoxyl 40 castor oil, polyoxyl 35 castor oil or polyoxyethylene castor oil.

[0019]

[10] The self-emulsifying composition according to any one of [1] to [9], further comprising a co-solvent.

[0020]

[11] A self-emulsifying drug delivery system in a formulation form suitable for oral administration, comprising the self-emulsifying composition according to any one of [1] to

[10] .

[0021]

[12] The self-emulsifying drug delivery system according to

[11] , wherein the formulation is a capsule. Petition 870250090533, dated 03 / 10 / 2025, page 17 / 60 / 41

[0022] In addition, as different aspects of the present disclosure, the following technical ideas are also provided.

[0023] [2-1] A treatment or prevention agent for a disease, comprising a self-emulsifying composition comprising: a sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof; and at least two solubilizers.

[0024] [2-2] The treatment agent or prevention agent according to [2-1], wherein the disease is an inflammatory disease for which an α4 integrin-dependent adhesion process is involved in a pathology.

[0025] [2-3] The treatment agent or prevention agent according to [2-1] or [2-2], wherein the disease is rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, multiple sclerosis, Sjogren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular disease, arteriosclerosis, restenosis, tumor growth, tumor metastasis, transplant rejection and / or human immunodeficiency virus infection.

[0026] [2-4] The treatment agent or prevention agent according to [2-3], where the disease is ulcerative colitis or Crohn's disease.

[0027] [2-5] A method for using a self-emulsifying composition comprising: a compound represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof; and at least two solubilizers, for treating or preventing a disease.

[0028] [2-6] The method according to [2-5], wherein the disease is an inflammatory disease for which an α4 integrin-dependent adhesion process is involved in a pathology.

[0029] [2-7] The method according to [2-5] or [2-6], where the disease is rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, multiple sclerosis, Sjogren's syndrome, asthma, psoriasis, allergy, Petition 870250090533, dated 03 / 10 / 2025, page 18 / 60 / 41 diabetes, cardiovascular disease, arteriosclerosis, restenosis, tumor growth, tumor metastasis, transplant rejection and / or human immunodeficiency virus infection.

[0030] [2-8] The method according to [2-7], where the disease is ulcerative colitis or Crohn's disease.

[0031] [2-9] Use of the self-emulsifying composition according to any of [1] to

[10] , to produce a treatment agent or a prevention agent for an inflammatory disease for which an α4 integrin-dependent adhesion process is involved in a pathology.

[0032] [2-10] Use in accordance with [2-9], where the disease is rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, multiple sclerosis, Sjogren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular disease, arteriosclerosis, restenosis, tumor growth, tumor metastasis, transplant rejection and / or human immunodeficiency virus infection.

[0033] [2-11] Use in accordance with [2-10], where the disease is ulcerative colitis or Crohn's disease.

[0034] [2-12] The self-emulsifying composition according to [3], wherein the fatty acid or a derivative thereof is an amide ester of a fatty acid, an ester of a fatty acid and a hydroxy acid, a sugar ester or a sugar ester derivative of a fatty acid, an ester of a fatty acid and a propylene glycol, an ester of a fatty acid and a glycerol, an ester of a fatty acid and a polyglycerol, an ester of a fatty acid and an ethylene glycol, an ester of a fatty acid and a polyethylene glycol, or an ester of a fatty acid and a macrogol glycerin.

[0035] In addition, as different aspects of the present disclosure, the following technical ideas are also provided.

[0036] [3-1] A self-emulsifying composition comprising: a sulfonamide derivative represented by formula (1), a salt Petition 870250090533, dated 03 / 10 / 2025, page 19 / 60 / 41 pharmaceutically acceptable thereof, or an active metabolite thereof; and at least two solubilizers, wherein the total content of the solubilizers is 10% by mass or more and 90% by mass or less in relation to the total mass of the self-emulsifying composition.

[0037] [3-2] The self-emulsifying composition according to [3-1], wherein the total content of solubilizers is 20% by mass or more and 90% by mass or less in relation to the total mass of the self-emulsifying composition.

[0038] [3-3] The self-emulsifying composition according to [3-1], wherein the total content of solubilizers is 30% by mass or more and 90% by mass or less in relation to the total mass of the self-emulsifying composition.

[0039] [3-4] The self-emulsifying composition according to [3-1], wherein the total content of solubilizers is 40% by mass or more and 90% by mass or less in relation to the total mass of the self-emulsifying composition.

[0040] [3-5] The self-emulsifying composition according to any one of [3-1] to [3-4], wherein the solubilizers comprise at least one surfactant, and the surfactant content is 5% by mass or more and 85% by mass or less relative to the total mass of the self-emulsifying composition.

[0041] [3-6] The self-emulsifying composition according to any one of [3-1] to [3-4], wherein the solubilizers comprise at least one surfactant, and the surfactant content is 10% by mass or more and 80% by mass or less relative to the total mass of the self-emulsifying composition.

[0042] [3-7] The self-emulsifying composition according to any one of [3-1] to [3-5], wherein the solubilizers comprise at least one auxiliary surfactant, and the content of the auxiliary surfactant is 5% by mass or more and 85% by mass or less relative to the total mass of the self-emulsifying composition.

[0043] [3-8] The self-emulsifying composition according to any one of [3-1] to [3-4] and [3-6], wherein the solubilizers comprise at least one auxiliary surfactant, and the content of the auxiliary surfactant is 10% in Petition 870250090533, dated 03 / 10 / 2025, page 20 / 60 / 41 mass or more and 80% by mass or less in relation to the total mass of the self-emulsifying composition.

[0044] [3-9] The self-emulsifying composition according to

[10] , wherein the cosolvent is one selected from the group consisting of acetic acid, sorbitol, mannitol, glycerol, triacetin, triethyl citrate, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, propylene carbonate, ethanol and propylene glycol.

[0045] [3-10] The self-emulsifying composition according to [3-9], wherein the cosolvent is ethanol or propylene glycol.

[0046] [3-11] The self-emulsifying composition according to any one of

[10] , [3-9] and [3-10], wherein the co-solvent content is 10% by mass or less relative to the total mass of the self-emulsifying composition.

[0047] [3-12] The self-emulsifying composition according to [3-11], wherein the co-solvent content is 8% by mass or less in relation to the total mass of the self-emulsifying composition.

[0048] [3-13] The self-emulsifying composition according to [3-12], wherein the co-solvent content is 5% by mass or less in relation to the total mass of the self-emulsifying composition.

[0049] [3-14] The self-emulsifying composition according to any one of [1] to

[10] , further comprising an additive.

[0050] [3-15] The self-emulsifying composition according to [3-14], wherein the additive is at least one selected from the group consisting of an excipient, a lubricant, a binder, a pH adjuster, a flavoring agent, a thickener, a buffering agent, a colorant, a diluent, a preservative and a sweetener.

[0051] [3-16] The self-emulsifying composition according to [2] or [4], a mass ratio of the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof to the Petition 870250090533, dated 03 / 10 / 2025, page 21 / 60 / 41 surfactant is 1:1 to 1:8.

[0052] [3-17] The self-emulsifying composition according to [2] or [5], a mass ratio of the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof to the auxiliary surfactant is 1:1 to 1:8.

[0053] [3-18] A self-emulsifying composition comprising 10 to 1000 mg of a sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof.

[0054] By providing a self-emulsifying composition comprising at least two solubilizers in addition to the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof, the present disclosure is capable of improving the absorbability of this compound, a pharmaceutically acceptable salt thereof, or an active metabolite thereof. Brief Description of the Figures

[0055] Fig. 1 is a graph showing a correlation between logarithmic values ​​(tube method Log(AUC0-2.25)) of the AUC of a tube method and logarithmic values ​​(rat PO / PK Log(AUC)) of the AUC of blood plasma concentrations.

[0056] Fig. 2 is a graph showing a correlation between logarithmic values ​​(tube method Log(AUC0-2.25)) of the tube method AUC and dissolution rates (%) at pH 2.4.

[0057] Fig. 3 is a graph showing a correlation between logarithmic values ​​(tube method Log(AUC0-2,25)) of the tube method AUC and dissolution rates (%) at pH 6.4. Description of the Modalities

[0058] Hereafter, this disclosure will be described in detail. Note that the modalities described below are an aspect of this disclosure. Petition 870250090533, dated 03 / 10 / 2025, page 22 / 60 11 / 41 disclosure and do not intend to limit the scope of this disclosure.

[0059] In the present disclosure, a sulfonamide derivative (sometimes referred to as “compound (1)” in the present Specification) represented by the following formula (1) is a compound that has an inhibitory action on integrin α4 and is also referred to as 2-methylpropyl(2S)-2-{2,5-difluoro-4-[4(2,2-dimethylpropylamide)phenylsulfonamide]benzamide}-3-{2-[1,6-dimethyl-2,4-dioxo-1,4-dihydropyrimidine-3(2H)-yl]pyridine-5-yl}propanoic acid. Those skilled in the art can recognize the scope of the present disclosure regardless of the nomenclature, provided the above compound is indicated. This compound can be obtained by a publicly known method, which is not limited to this one, but includes a method described in International Publication No. WO2017 / 135472 or similar, for example, as a synthesis method.

[0060] In the present disclosure, the “pharmaceutically acceptable salt” needs to be only a pharmaceutically acceptable salt in which the sulfonamide derivative represented by formula (1) above can be in the form of a salt, while retaining pharmacological activity, and includes, for example, an ammonium salt; an alkali metal salt of sodium, potassium or similar; an alkaline earth metal salt of calcium, magnesium or similar; an aluminum salt; a zinc salt; a salt with an organic amine, such as triethylamine, Petition 870250090533, dated 03 / 10 / 2025, page 23 / 60 / 41 ethanolamine, morpholine, piperidine or dicyclohexylamine; a salt with a basic amino acid, such as arginine or lysine, for an acidic group, such as a carboxyl group in the formula. Furthermore, for a basic group in the formula, the pharmaceutically acceptable salt includes a salt with an inorganic acid, such as hydrochloric acid, sulfuric acid or phosphoric acid; a salt with an organic carboxylic acid, such as acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid or succinic acid; and a salt with an organic sulfonic acid, such as methanesulfonic acid or ptoluenesulfonic acid.Furthermore, as a method for forming a salt, a publicly known method may be used as appropriate, and the method includes, for example, mixing the sulfonamide derivative represented by formula (1) with a required acid or base in an appropriate proportion in a solvent or dispersion medium, or the salt may be converted from another form of a salt by a method such as ion exchange.

[0061] In this disclosure, the “active metabolite” refers to a group of compounds with α4 integrin inhibitory action among compounds in which the sulfonamide derivative represented by formula (1) above is converted by an enzyme, a gastrointestinal tract fluid or similar under physiological conditions in vivo. The conversion reaction includes reductions such as oxidation, reduction and hydrolysis. A non-limiting example of the active metabolite includes a compound represented by the following formula (2) (sometimes referred to as a “compound (2)” in this Descriptive Report). Petition 870250090533, dated 03 / 10 / 2025, page 24 / 60 13 / 41

[0062] A “self-emulsifying composition” refers to a composition that has the property of being able to emulsify to form an emulsion in an aqueous medium (self-emulsifying property) and includes a self-nanoemulsifying composition and a self-microemulsifying composition. An emulsion to be formed can have any size and therefore all self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS) and self-nanoemulsifying drug delivery systems (SNEDDS), which are generally distinguished according to the diameter of the emulsion, belong to the scope of the self-emulsifying composition in this disclosure.

[0063] The self-emulsifying composition in this disclosure can be prepared by a publicly known method. Furthermore, the properties of the self-emulsifying composition thus prepared can be evaluated by publicly known methods, as appropriate. In a non-limiting aspect of evaluating the properties of a self-emulsifying composition, particle size and the like are known as indices representing the physical properties of an emulsion, for example. As a method for evaluating particle size, a conventionally known method can be used. For example, dynamic light scattering (DLS) can be used. In addition, as a parameter reflecting particle size, a method can also be used for Petition 870250090533, dated 03 / 10 / 2025, page 25 / 60 / 41 assess turbidity using a turbidimeter.

[0064] In the self-emulsifying composition of the present disclosure, the content of the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is not particularly limited, but is preferably 10 mg or more, more preferably 50 mg or more, and even more preferably 100 mg or more, and preferably 1000 mg or less, more preferably 800 mg or more, and even more preferably 400 mg or less. Furthermore, in the self-emulsifying composition of the present disclosure, the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is preferably contained in an amount of 10 to 1000 mg, more preferably contained in an amount of 50 to 800 mg, and even more preferably contained in an amount of 100 to 400 mg.When the total mass of the self-emulsifying composition of the present disclosure is considered to be 100%, the content of the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is preferably 1% by mass or more and more preferably 5% by mass or more, and preferably 50% by mass or less and more preferably 30% by mass or less.

[0065] The self-emulsifying composition of this disclosure contains at least two solubilizers. A “solubilizer” means a suitable means that can increase the solubility of a target solute. Solubilizers are not particularly limited within the scope of this disclosure, provided they are publicly known as solubilizers, but preferably include solubilizers belonging to either a cyclodextrin (e.g., β-cyclodextrin or γ-cyclodextrin), a cyclodextrin derivative (e.g., sulfobutyl or hydroxypropyl ether), bile acid, a bile acid derivative (e.g., cholate, ursodeoxycholate, Petition 870250090533, dated 03 / 10 / 2025, page 26 / 60 / 41 chenodeoxycholate, taurochenodeoxycholate, taurourusodeoxycholate, glucochenodeoxycholate or glucourusodeoxycholate), a fatty acid (for example, capric acid, caprylic acid, lauric acid, sarcosine acid, palmitic acid, myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, ricinoleic acid, arachidonic acid, behenic acid and pharmaceutically acceptable salts thereof), a fatty acid derivative, an alcohol, a fatty alcohol (for example, stearyl alcohol), a fatty alcohol derivative (for example, polyethylene glycol octadecyl ether), as well as a tocol derivative. A preferred fatty acid derivative includes sodium salt of dioctyl sulfosuccinate, sodium lauryl sulfate, an amide ester of a fatty acid (e.g., lauric acid diethanolamide, sodium lauroyl sarcosinate, lauroylcarnitine, palmitoylcarnitine, or myristoylcarnitine).a fatty acid or fatty alcohol ester and a hydroxy acid (e.g., sodium stearoyl lactylate or lauryl lactate), a sugar ester and a sugar ester derivative of a fatty acid (e.g., glucose monocaprylate, diglucose monocaprylate, sucrose laurate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monooleate, sorbitan monostearate, sorbitan tristearate, sucrose myristate or polyoxyethylene (20) sorbitan oleate (Polysorbate 80)), a fatty acid ester of a lower alcohol, an ester of a fatty acid and a propylene glycol, an ester of a fatty acid and a glycerol, an ester of a fatty acid and a polyglycerol, an ester of a fatty acid and an ethylene glycol, an ester of a fatty acid and a polyethylene glycol, an ester of a fatty acid and a macrogol glycerin (also called polyoxyglycerol), a triglyceride (e.g., corn oil, almond oil, coconut oil, castor oil,hydrogenated castor oil or hydrogenated coconut oil), a mixture of a fatty acid ester and a propylene glycol and a fatty acid ester and a macrogol glycerin and a polyglycerized fatty acid.

[0066] As a total content of solubilizers, solubilizers can be Petition 870250090533, dated 03 / 10 / 2025, page 27 / 60 / 41 mixed in a desired proportion, provided that an emulsion is formed and a self-emulsifying property is exhibited. For example, when the total mass of the self-emulsifying composition is considered to be 100%, the total content of the solubilizers may be 10% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, or 50% by mass or more. For example, when the total mass of the self-emulsifying composition is considered to be 100%, the total content of the solubilizers may be 90% by mass or less. Although not limited to this, when the total mass of the self-emulsifying composition is considered to be 100%, the total content of the solubilizers may be 10% by mass or more and 90% by mass or less.The total content of solubilizers is preferably 20% by mass or more and 90% by mass or less, more preferably 30% by mass or more and 90% by mass or less, even more preferably 40% by mass or more and 90% by mass or less, even more preferably 50% by mass or more and 90% by mass or less, and particularly preferably 60% by mass or more and 90% by mass or less.

[0067] In addition, in one aspect of the present disclosure, the solubilizers contain at least one surfactant and at least one auxiliary surfactant.

[0068] The term “surfactant” refers to a group that exhibits lipophilicity among those belonging to the solubilizers above. Although not limited to this, as an index of lipophilicity, the hydrophilic-lipophilic balance (HLB) can be used. The HLB is obtained by the equal division of substances that do not have a hydrophilic group as HLB=0 and substances that do not have a lipophilic group as HLB=20, and can be calculated by a method known to a specialist in the field, such as the Griffin method, for example. In this disclosure, HLB means a value calculated by the Griffin method. In general, the lower the HLB, the greater the lipophilicity. Therefore, in the self-emulsifying composition of the present disclosure, a solubilizer with an HLB Petition 870250090533, dated 10 / 03 / 2025, p. 28 / 60 / 41. A relatively small surfactant may be selected as appropriate. For example, in this disclosure, a solubilizer with an HLB of 7 or less may be selected as the “surfactant”. Specifically, the surfactant is an ester of a fatty acid and propylene glycol, an ester of a fatty acid and glycerol, or an ester of a fatty acid and polyglycerol (HLB<7), and is more specifically, polyglyceryl-2 dioleate, polyglyceryl-3 dioleate, polyglyceryl-10 trioleate, propylene glycol monolaurate, propylene glycol monocaprylate, glyceryl monocaprylate, glyceryl monolaurate, glyceryl dilaurate, glyceryl monolinoleate, or the like. These surfactants can be synthesized by a publicly known method, as appropriate, or they can be obtained commercially.Non-limiting examples of commercial products include commercially available products that have names such as Caprol, Capriol, Capmul, Lauroglycol, and Plurol Oleique in parts of their product names. One of these surfactants may be used alone, or two or more of them may be combined.

[0069] When the total mass of the self-emulsifying composition of the present disclosure is considered to be 100%, the surfactant content is preferably 5% by mass or more and more preferably 10% by mass or more, and preferably 85% by mass or less and more preferably 80% by mass or less. Furthermore, when the content of the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is considered to be 1 in terms of the sulfonamide derivative represented by formula (1), the surfactant content is 0.1 or more, preferably 0.5 or more, and more preferably 1.0 or more, and is 10 or less, preferably 9.5 or less, and more preferably 9 or less. In addition, the surfactant may be added such that a mass ratio between the sulfonamide derivative represented by formula (1), a salt Petition 870250090533, dated 03 / 10 / 2025, p. 29 / 60 / 41 pharmaceutically acceptable of the same, or an active metabolite thereof, and the surfactant is within a range of 1:1 to 1:10, and preferably 1:1 to 1:8.

[0070] The “auxiliary surfactant” refers to a group that exhibits hydrophilicity among those belonging to the solubilizers above. In general, the higher the HLB mentioned above, the greater the hydrophilicity. Therefore, in the self-emulsifying composition of the present disclosure, a solubilizer with a relatively large HLB may be selected as an auxiliary surfactant, as appropriate. For example, in the present disclosure, a solubilizer with an HLB greater than 7 may be selected as the “auxiliary surfactant”. Specifically, the auxiliary surfactant is an ester of a fatty acid and a polyglycerol (HLB>7), an ester of a fatty acid and an ethylene glycol, an ester of a fatty acid and a polyethylene glycol, an ester of a fatty acid and a macrogol glycerin, a fatty alcohol derivative or a tocol derivative and is more specifically, castor oil polyoxyl 40, castor oil polyoxyl 35, PEG-25 trioleate, PEG-60 corn glycerides, PEG-60 almond oil, PEG-40 palm kernel oil,PEG-50 castor oil, PEG-50 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-8 caprylic / capric glycerides, polyoxyl-32 lauroyl glycerides, polyoxyl-6 linoleyl glycerides, polyoxyl-6 oleoyl glycerides, polyoxyl-32 stearoyl glycerides, PEG-6 caprylic / capric glycerides, polyglyceryl-10 monooleate, polyglyceryl-10 laurate, polyglyceryl-15 hydroxystearate or PEG α-tocopherol succinate (e.g., PEG-400 tocopherol succinate, PEG-1000 α-tocopherol succinate, dl-tocopherol succinate) PEG-1000 or PEG-1000 da-tocopherol succinate). In addition, these auxiliary surfactants may be synthesized by a publicly known method, as appropriate, or may be obtained commercially. Non-limiting examples of commercial products include commercially available products that have names such as Kolliphor, Cremophor, Petition 870250090533, dated 03 / 10 / 2025, pages 30 / 60 / 41 Labrafil, Labrasol, Gellucire, and TPGS are parts of their product names. One of these auxiliary surfactants can be used alone, or two or more of them can be combined.

[0071] Among the auxiliary surfactants listed as described above, the ester of a fatty acid and a macrogol glycerin includes castor oil polyoxyl 40, castor oil polyoxyl 35, PEG-25 trioleate, PEG-60 corn glycerides, PEG-60 almond oil, PEG-8 caprylic / capric glycerides, lauroyl polyoxyl-32 glycerides, linoleyl polyoxyl-6 glycerides, oleoyl polyoxyl-6 glycerides, stearoyl polyoxyl-32 glycerides and PEG-6 caprylic / capric glycerides, the ester of a fatty acid and a polyglycerol includes polyglyceryl-10 monooleate, polyglyceryl-10 laurate and polyglyceryl-15 hydroxystearate, the ester of a fatty acid Polyethylene glycol includes PEG-50 hydrogenated castor oil and PEG-60 hydrogenated castor oil, and tocopherol derivatives include PEG-400 α-tocopherol succinate, PEG-1000 α-tocopherol succinate, PEG-1000 dl-α-tocopherol succinate, and PEG-1000 dα-tocopherol succinate.As an ester of a fatty acid and a macrogol glycerin, the average number of moles of polyethylene glycol added is preferably 20 or more, and more preferably 32 or more. An ester of a fatty acid and a macrogol glycerin with an average number of moles of polyethylene glycol added of 32 or more includes polyoxyl 40 castor oil, polyoxyl 35 castor oil, PEG-60 corn glycerides, PEG-60 almond oil, polyoxyl-32 lauroyl glycerides, and polyoxyl-32 stearoyl glycerides.

[0072] When the total mass of the self-emulsifying composition of the present disclosure is considered to be 100%, the content of the auxiliary surfactant is preferably 5% by mass or more and more preferably 10% by mass or more, and preferably 85% by mass or less and more preferably 80% by mass or less. Furthermore, when the content of the sulfonamide derivative represented by formula (1), a salt Petition 870250090533, dated 03 / 10 / 2025, p. 31 / 60 / 41 pharmaceutically acceptable thereof, or an active metabolite thereof, is considered to be 1 in terms of the sulfonamide derivative represented by formula (1), the content of the auxiliary surfactant is 0.1 or more, preferably 0.5 or more, and more preferably 1.0 or more, and is 10 or less, preferably 9.5 or less, and more preferably 9 or less. Furthermore, the auxiliary surfactant may be added such that a mass ratio between the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof and the auxiliary surfactant is within a range of 1:1 to 1:10, and preferably 1:1 to 1:8.

[0073] The surfactant and the surfactant auxiliary may be mixed in the desired ratio, provided that an emulsion is formed and a self-emulsifying property is exhibited. For example, the ratio between surfactant and surfactant auxiliary may be 1:1 or more, 1:2 or more, or 1:3 or more. For example, the ratio between surfactant and surfactant auxiliary may be 1:10 or less, 1:9 or less, or 1:8 or less. Although not limited to this, the ratio between surfactant and surfactant auxiliary is, for example, 1:1 or more and 1:10 or less, preferably 1:2 or more and 1:9 or less, and more preferably 1:3 or more and 1:8 or less.

[0074] Furthermore, the total content of the surfactant and auxiliary surfactant may be mixed in a desired proportion, provided that an emulsion is formed and a self-emulsifying property is exhibited. For example, when the total mass of the self-emulsifying composition is considered to be 100%, the total content of the surfactant and auxiliary surfactant may be 10% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, or 50% by mass or more. For example, when the total mass of the self-emulsifying composition is considered to be 100%, the total content of the surfactant and auxiliary surfactant may be 90% by mass or less. Although not limited to this, when the total mass of the composition Petition 870250090533, dated 03 / 10 / 2025, p. 32 / 60 / 41 self-emulsifying agent is considered as 100%, the total content of surfactant and auxiliary surfactant may be 10% by mass or more and 90% by mass or less. The total content of surfactant and auxiliary surfactant may preferably be 20% by mass or more and 90% by mass or less, more preferably 30% by mass or more and 90% by mass or less, even more preferably 40% by mass or more and 90% by mass or less, even more preferably 50% by mass or more and 90% by mass or less, and particularly preferably 60% by mass or more and 90% by mass or less.

[0075] The self-emulsifying composition of this disclosure may further comprise a cosolvent. The cosolvent includes acetic acid, sorbitol, mannitol, glycerol, triacetin, triethyl citrate, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, propylene carbonate, ethanol, propylene glycol and the like. These cosolvents may be synthesized by a publicly known method, as appropriate, or may be obtained commercially. One of these cosolvents may be used alone, or two or more of them may be combined.

[0076] In the self-emulsifying composition of the present disclosure, the cosolvent may be mixed in a desired proportion, provided that the self-emulsifying composition forms an emulsion and exhibits a self-emulsifying property. The proportion of the cosolvent is desirably as small as possible from the point of view of the commercial production of a self-emulsifying drug delivery system comprising the self-emulsifying composition of the present disclosure and its use in clinical settings. For example, although not limited to this, when the total mass of the self-emulsifying composition is considered to be 100%, the cosolvent content may be 1% by mass or more and 15% by mass or less. The cosolvent may preferably be 1% by mass or more and 10% by mass or less, more preferably 1% by mass or more and 8% by mass or less. Petition 870250090533, dated 03 / 10 / 2025, p. 33 / 60 / 41 mass or less, even more preferably 1% by mass or more and 5% by mass or less, and particularly preferably 2% by mass.

[0077] In the self-emulsifying composition of the present disclosure, a preferred combination of the surfactant, the auxiliary surfactant and the cosolvent is not particularly limited, provided that the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof or an active metabolite thereof can be dissolved and a self-emulsifying property is exhibited.However, for example, a combination of a fatty acid ester and propylene glycol as a surfactant, a fatty acid ester and a macrogol glycerin or tocopherol derivative as an auxiliary surfactant, and ethanol as a cosolvent is preferred, and a combination of propylene glycol monolaurate or propylene glycol monocaprylate as a surfactant, polyoxyl 40 castor oil, polyoxyl 35 castor oil or PEG-1000 α-tocopherol succinate as an auxiliary surfactant, and ethanol as a cosolvent is more preferable, and a combination of propylene glycol monocaprylate as a surfactant, polyoxyl 35 castor oil as an auxiliary surfactant, and ethanol as a cosolvent is particularly preferred.

[0078] In the self-emulsifying composition of this disclosure, a preferred mixing ratio of the surfactant, auxiliary surfactant and cosolvent is not particularly limited, provided that the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof or an active metabolite thereof can be dissolved and a self-emulsifying property is exhibited, but, for example, the mixing ratio in surfactant:auxiliary surfactant:cosolvent is preferably any one of 45:45:10, 40:50:10, 30:60:10, 22.5:67.5:10, 10:80:10, 11:84:5 or 11:87:2, more preferably any one of 10:80:10, 11:84:5 or 11:87:2 and particularly preferably 11:87:2. Petition 870250090533, dated 03 / 10 / 2025, p. 34 / 60 / 41

[0079] The self-emulsifying composition of this disclosure may further comprise an additive. The additive is not particularly limited, provided it is pharmaceutically acceptable and the self-emulsifying composition exhibits a self-emulsifying property, but the additive includes, for example, an excipient, a lubricant, a binder, a pH adjuster, a flavoring agent, a thickener, a buffering agent, a colorant, a diluent, a preservative and / or a sweetener and the like. As well as these additives, one of the publicly known additives may be used alone, or two or more of them may be used in combination. The amount of mixing of these additives may be in any desired proportion, as appropriate, provided the self-emulsifying composition exhibits self-emulsifying capability.

[0080] The self-emulsifying composition of the present disclosure can be pharmaceutically formulated by a publicly known method as appropriate and used in the treatment or prevention of diseases described herein as a self-emulsifying drug delivery system. Preferably, as a step towards pharmaceutical formulation, various pharmaceutical formulation techniques may be used, provided that the self-emulsifying composition can be used as SEDDS, SMEDDS and / or SNEDDS and exhibits a self-emulsifying property. More preferably, a pharmaceutical formulation technique capable of preparing a formulation suitable for oral administration may be selected.Here, "formulation suitable for oral administration" refers to any form of solution, water- or oil-based suspension, syrup, elixir, emulsion, tablet, pill, pellet, granules, fine granules, powder, capsule containing granules, fine granules or powder, capsule containing a solution or suspension, sustained-release system and the like. More preferably, the formulation suitable for oral administration is a capsule, and may be a capsule containing fine granules or a powder or a... Petition 870250090533, dated 03 / 10 / 2025, page 35 / 60 / 41 capsule containing a solution or a suspension.

[0081] The capsule may be a hard capsule or a soft capsule, but is preferably a soft capsule. The composition of the soft capsule film is not necessarily limited, and its main component includes, for example, gelatin, carrageenan, pectin, pullulan, sodium alginate, starch, hypromellose, hydroxypropylcellulose and the like, as well as various publicly known components, but is preferably gelatin. The gelatin is not particularly limited, provided it is commercially available.

[0082] As the self-emulsifying composition of the present disclosure contains the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof, the self-emulsifying composition of the present disclosure can be used as a treatment agent or a prevention agent having an α4 integrin inhibitory action. Herein, “treatment” refers to the improvement of clinical symptoms related to diseases or disorders, i.e., complete cure, reduction in the degree or frequency of clinical symptoms, or the introduction or maintenance of remission conditions, and includes actions conducted on living organisms of the treatment subject for such and similar conditions, and “prevention” refers to the reduction of the risks of developing diseases or disorders, and includes actions conducted on living organisms that have not contracted diseases or living organisms that are not exhibiting clinical symptoms to prevent diseases from developing and similar conditions.

[0083] Diseases that can be effectively treated or prevented using the self-emulsifying composition of the present disclosure or a treatment or prevention agent containing the self-emulsifying composition include inflammatory diseases for which an α4 integrin-dependent adhesion process is involved in the pathologies. Specifically, such diseases are inflammatory diseases in which the integrin Petition 870250090533, of 03 / 10 / 2025, page 36 / 60 / 41 α4 is involved in an adhesion process between epithelial cells of blood vessels and cells related to inflammation and, more specifically, are diseases that can be treated or prevented by the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof, inhibiting integrin α4 to prevent inflammation-related cells from infiltrating from the epithelium of blood vessels into the tissues. Although not limited to these, such diseases include, for example, rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, multiple sclerosis, Sjögren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular disease, arteriosclerosis, restenosis, tumor growth, tumor metastasis, transplant rejection and / or infection with the human immunodeficiency virus and similar conditions.

[0084] When administered orally in an amount effective for treatment or in an amount sufficient for treatments, the self-emulsifying drug delivery system or treatment agent of this disclosure exhibits useful therapeutic effects in the above diseases. Herein, “amount effective for treatment” and “amount sufficient for treatments” have the same meaning and refer to an amount effective or sufficient to exhibit the efficacy of the drug in the case where the pharmaceutical agent is administered to a living organism to treat a disease and may be determined in various ways depending on the gender, age, physical size, disease type, disease grade, lifestyle habits and the like of a living organism.

[0085] The self-emulsifying composition, the self-emulsifying drug delivery system, the treatment agent and / or the prevention agent of the present disclosure have properties of being emulsified when administered orally to a living organism and then mixed with the fluid of the gastrointestinal tract. In addition, emulsification allows the sulfonamide derivative represented by formula (1) or a salt Petition 870250090533, dated 03 / 10 / 2025, page 37 / 60 / 41, pharmaceutically acceptable, the same being dissolved from an emulsion formed by the self-emulsifying drug delivery system. Herein, "gastrointestinal tract fluid" refers to a liquid component secreted by a living organism into the oral cavity, esophagus, stomach, small intestine, large intestine, and the like, or a liquid component present in the gastrointestinal tract, and specifically refers to saliva, gastric acid, bile, pancreatic juice, intestinal juice, and the like. As these gastrointestinal tract fluids have various liquid properties, from an acidic to a neutral condition, the self-emulsifying drug delivery system preferably has properties that allow the compound to be dissolved from an emulsion formed as the self-emulsifying drug delivery system passes within the gastrointestinal tract after oral administration.More preferably, it has properties that allow the compound to be dissolved from an emulsion formed within a pH range from an acidic to a neutral condition exhibited by the gastrointestinal tract fluid; even more preferably, it has properties that allow the compound to be dissolved from an emulsion formed within a wide pH range from an acidic to a neutral condition; and particularly preferably, it has properties that allow the compound to be dissolved from an emulsion formed within a wide pH range from an acidic to a neutral condition and allows the compound to be dissolved more readily in an acidic condition than in a neutral condition. Here, the acidic condition is typically a condition mixed with gastric acid in the stomach and generally refers to a pH between 2.0 and 3.0. The neutral condition is normally a condition mixed with bile.Pancreatic juice, or intestinal juice, is found in the small or large intestine and generally has a pH between 6.0 and 7.5.

[0086] In one aspect of the present disclosure, for example, the Petition 870250090533, dated 03 / 10 / 2025, page 38 / 60 / 41 self-emulsifying drug delivery system has properties that allow the compound to be dissolved more easily under acidic conditions than in the case where the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is dissolved in an aqueous methylcellulose solution. Furthermore, in one aspect of the present disclosure, for example, the self-emulsifying drug delivery system has properties that allow the compound to be dissolved more easily under acidic conditions than in the case where the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is dissolved in a polyethylene glycol solution.

[0087] The absorbability of the self-emulsifying composition, the self-emulsifying drug delivery system, the treatment agent and / or the prevention agent in the gastrointestinal tract can be obtained directly or indirectly through an experimental evaluation. Specifically, absorbability can be evaluated by exposing the self-emulsifying composition to the acidic condition up to the neutral condition and can be evaluated in an in vitro or in vivo experiment. Although not limited to this, as in the in vitro experiment, for example, the Tube method, which will be described later, can be used. In addition, although not limited to this, as in the in vivo experiment, for example, a PO / PK experiment in which blood is collected over time after the self-emulsifying composition is administered orally to rodents or non-rodents and then the blood concentration of an active pharmaceutical ingredient and / or an active metabolite thereof is analyzed.Non-rodents are typically dogs, monkeys, or humans. By plotting the blood concentration thus obtained on the vertical axis and the elapsed time period on the horizontal axis, a curve indicating a change in blood concentration over time can be illustrated, and an area under the curve (AUC) of that curve can also be used for assessment of... Petition 870250090533, dated 03 / 10 / 2025, pp. 39 / 60 / 41 absorbability.

[0088] In one aspect of the present disclosure, for example, the self-emulsifying drug delivery system exhibits a higher AUC than in the case where the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is dissolved in an aqueous methylcellulose solution. Furthermore, in one aspect of the present disclosure, it is preferable that the self-emulsifying drug delivery system exhibits a higher AUC than in the case where the sulfonamide derivative represented by formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof is dissolved in a polyethylene glycol solution.

[0089] From the point of view of facilitating the assessment, it is preferable to use the tube method as an in vitro experiment, for example. The tube method is an experimental method as follows. A solution of a self-emulsifying composition in which a certain amount of a compound is dissolved is prepared and first added to a test liquid mimicking an acidic condition in the stomach, and then a small amount of the test liquid is collected after a lapse of a desired period of time. Subsequently, the test liquid is added in a way that mimics the neutral condition of the small intestine, and the same operation is repeated. Subsequently, the test liquid is added in a way that mimics the neutral condition of the large intestine, and the same operation is repeated.Therefore, absorbability can be assessed indirectly from the dissolution rate under each condition by quantifying the amount of the compound in each test liquid obtained as described above by a known analytical method, such as a high-performance liquid chromatography method, a gas chromatography method, a supercritical fluid chromatography method, or a mass spectrometry method.

[0090] Here, the “dissolution rate” in this Specification is a Petition 870250090533, dated 03 / 10 / 2025, page 40 / 60 / 41, a numerical value such that when the amount of a compound dissolved in a solution of a desired self-emulsifying composition is considered to be 100%, after the solution is mixed with a given test liquid, the numerical value is obtained by expressing the amount of the compound dissolved in an emulsion formed in the test liquid as a percentage. Furthermore, by plotting the concentration of the compound in the test liquid obtained under each experimental condition on the vertical axis and the elapsed time on the horizontal axis, a curve indicating a change in the concentration of the compound in the test liquid over time can be illustrated, and an AUC of this curve can also be used for absorbability assessment. Examples

[0091] Hereafter, the invention of the present disclosure will be described in detail using Examples. (Production Example 1) Preparation of Self-Emulsifying Compositions 1 to 84

[0092] Each surfactant, auxiliary surfactant and cosolvent were weighed and mixed, and an active pharmaceutical ingredient (compound (1)) was added to the mixture thus obtained, followed by treatment using an ultrasonic homogenizer at 50°C to prepare the self-emulsifying compositions 1 to 84 shown in Table 1 to Table 7. Each numerical value in Table 1 to Table 7 represents % by mass. Table 1 No. 1 2 3 4 5 6 7 8 9 10 Active pharmaceutical ingredient 5 5 5 5 5 5 5 5 5 5 Capriol 90 9.5 47.5 42.75 9.5 42.75 9.5 - 42.75 42.75 9.5 Capmul MCM C8 - - - - - - 42.75 - - - Labrasol ALF 85.5 47.5 42.75 76 - - - 42.75 - - Kolliphor EL - - - - 42.75 76 42.75 - 42.75 76 Propylene glycol - - 9.5 9.5 9.5 9.5 9.5 - - - Ethanol - - - - - - - 9.5 9.5 9.5 Petition 870250090533, dated 03 / 10 / 2025, page 41 / 60 / 41 Table 2 No. 11 12 13 14 15 16 17 18 19 20 21 22 Active pharmaceutical ingredient 5 5 5 5 5 5 5 5 5 5 5 5 Capriol 90 42.75 38 28.5 21.37 5 9.5 47.5 47.5 - - 57 66.5 76 Capmul MCM C8 - - - - - - - 47.5 47.5 - - - Kolliphor EL - 38 28.5 21.37 5 9.5 47.5 47.5 28.5 19 9.5 Tween 80 - - - - - - 47.5 - 47.5 - - - TPGS 42.75 9.5 28.5 42.75 66.5 - - - - - - - Ethanol 9.5 9.5 9.5 9.5 9.5 - - - - 9.5 9.5 9.5 Table 3 No. 23 24 25 26 27 28 29 30 31 32 33 34 Active pharmaceutical ingredient 10 10 10 10 10 10 10 10 10 10 10 10 Capriol 90 40.5 36 27 20.25 9 40.5 9 40.5 40.5 - - 40.5 Capmul MCM C8 - - - - - - - - - 40.5 45 - Kolliphor EL - 36 27 20.25 9 40.5 72 40.5 40.5 - - - Kolliphor RH40 - - - - - - - - - 40.5 45 40.5 TPGS 40.5 9 27 40.5 63 - - - - - Propylene Glycol - Propylene Carbonate - Ethanol - Ethanol Table 4 No. 35 36 37 38 39 40 41 42 43 44 45 46 Active pharmaceutical ingredient 10 10 10 10 10 10 10 10 10 10 10 10 Capriol 90 40.5 40.5 40.5 - - - - - - - - Capmul MCM C8 40.5 - - - - - - - - - - - Plurol Oleique CC497 - - - - 40.5 40.5 40.5 40.5 40.5 - - - Lauroglycol 90 - - - - - - - - - 40.5 40.5 40.5 Labrasol ALF - - - - - 40.5 - - - - - - Kolliphor EL 40.5 - - - - - - - - - 40.5 - Kolliphor RH40 - - - - - - - - - - - 40.5 Kolliphor HS15 - - - - - - - - - 40.5 - - Gelucire 44 / 14 - 40.5 - - - - 40.5 - - - - - Gelucire 48 / 16 - - 40.5 - - - - - - - - - Gelucire 50 / 13 - - - 40.5 - - - - - - - - TPGS - - - - - - - 40.5 - - - - Petition 870250090533, dated 03 / 10 / 2025, page 42 / 60 / 41 Tween 80 - - - - 40.5 - - - - - - - BRIJ S10 - - - - - - - - 40.5 - - - Ethanol 9 9 9 9 9 9 9 9 9 9 9 9 Table 5 No. 47 48 49 50 51 52 53 54 55 56 57 58 Active pharmaceutical ingredient 10 10 10 10 10 10 10 10 10 10 10 10 Lauroglycol 90 40.5 40.5 40.5 40.5 40.5 40.5 - - - - - - Lauroglycol FCC - - - - - - 40.5 40.5 40.5 40.5 40.5 40.5 Labrasol ALF - 40.5 - - - - - - - - 40.5 - Kolliphor EL - - - - - - - 40.5 - - - - Kolliphor RH40 - - - - - - - - 40.5 - - - Kolliphor HS15 - - - - - - 40.5 - - - - - Gelucire 44 / 14 - - 40.5 - - - - - - - - 40.5 Gelucire 50 / 13 - - - 40.5 - - - - - - - - TPGS - - - - 40.5 - - - - - - - Tween 80 40.5 - - - - - - - - 40.5 - - BRIJ S10 - - - - - 40.5 - - - - - - Ethanol 9 9 9 9 9 9 9 9 9 9 9 9 Table 6 No. 59 60 61 62 63 64 65 66 67 68 69 70 Active pharmaceutical ingredient 10 10 10 10 10 10 10 10 10 10 10 10 Lauroglycol FCC 40.5 40.5 40.5 - - - - - - - - - Capriol PGMC - - - 40.5 40.5 40.5 40.5 40.5 40.5 40.5 40.5 40.5 Labrasol ALF - - - - - - - 40.5 - - - - Kolliphor EL - - - - 40.5 - - - - - - - Kolliphor RH40 - - - - - 40.5 - - - - - - Kolliphor HS15 - - - 40.5 - - - - - - - - Gelucire 44 / 14 - - - - - - - - 40.5 - - - Gelucire 50 / 13 40.5 - - - - - - - - 40.5 - - TPGS - 40.5 - - - - - - - - 40.5 - Tween 80 - - - - - - 40.5 - - - - - BRIJ S10 - - 40.5 - - - - - - - - 40.5 Ethanol 9 9 9 9 9 9 9 9 9 9 9 9 Petition 870250090533, dated 03 / 10 / 2025, page 43 / 60 / 41 Table 7 No. 71 72 73 74 75 76 77 78 79 80 81 82 83 84 Active pharmaceutical ingredient 10 10 10 10 10 10 10 10 10 10 10 10 10 10 Capriol 90 40.5 40.5 40.5 40.5 40.5 40.5 - 40.5 - - - - - - Capmul MCM C8 - - - - - - 40.5 - 40.5 40.5 40.5 40.5 40.5 Labrasol ALF - - - - - - - 40.5 - 40.5 - - - - Kolliphor HS15 40.5 - - - - - 40.5 - - - - - - - Gelucire 44 / 14 - - - - - - - - - - 40.5 - - - Gelucire 50 / 13 - - - - - - - - - - - 40.5 - - TPGS - - - - - - - - - - - - 40.5 - Tween 80 - - - 40.5 - - - - 40.5 - - - - - BRIJ S10 - - - - 40.5 - - - - - - - - 40.5 LABRAFIL M2125CS - 40.5 - - - - - - - - - - - - LABRAFIL M1944CS - - 40.5 - - - - - - - - - - - Sucrose myristate - - - - - 40.5 - - - - - - - - Ethanol 9 9 9 9 9 9 9 9 9 9 9 9 9 9

[0093] The surfactants shown in Tables 1 to 7 above are as follows.

[0094] • Capriol 90: Propylene glycol monocaprylate (type II) • Capmul MCM C8: Glyceryl monocaprylate • Plurol Oleique CC497: Polyglyceryl-3-dioleate • Lauroglicol 90: Propylene glycol monolaurate (type II) • Lauroglicol FCC: Propylene glycol monolaurate (type I) • Capriol PGMC: Propylene glycol monocaprylate (type I)

[0095] The auxiliary surfactants indicated in Tables 1 to 7 above are as follows.

[0096] • Labrasol ALF: PEG-8 caprylic / capric glycerides • Kolliphor EL: Polyoxyl 35 castor oil • Kolliphor RH40: Polyoxyl 40 castor oil • Kolliphor HS15: Polyglyceryl-15 hydroxystearate • Gelucire 44 / 14: Polyoxyl-32 lauroyl glycerides • Gelucire 48 / 16: Polyoxyl-32 stearoyl glycerides Petition 870250090533, dated 03 / 10 / 2025, pages 44 / 60 / 41 • Gelucire 50 / 13: Stearoyl polyoxyl-32 glycerides • TPGS: PEG-1000 da-Tocopherol succinate • Tween 80: Polysorbate 80 • BRIJ S10: Polyethylene glycol octadecyl ether • LABRAFIL M2125CS: Linoleoyl polyoxyl-6 glycerides • LABRAFIL M1944CS: Oleoyl polyoxyl-6 glycerides • Sucrose myristate

[0097] Among the self-emulsifying compositions in Production Example 1, the correspondences of self-emulsifying compositions that have the same component composition, except for concentrations, and have the same component ratio, except for the active pharmaceutical ingredients, are shown in Table 8. Self-emulsifying compositions 85 to 87 were prepared in accordance with Production Example 1. Self-emulsifying composition 85 contained 1.5% by mass of the active pharmaceutical ingredient, 44.325% by mass of Capriol 90, 44.325% by mass of Labrasol ALF, and 9.85% by mass of ethanol. Self-emulsifying composition 86 contained 1.5% by mass of the active pharmaceutical ingredient, 44.325% by mass of Capriol 90, 44.325% by mass of Kolliphor EL, and 9.85% by mass of ethanol. The self-emulsifying composition 87 contained 1.5% by mass of the active pharmaceutical ingredient, 9.85% by mass of Capriol 90, 78.8% by mass of Kolliphor EL and 9.85% by mass of ethanol. Table 8 Concentration of active pharmaceutical ingredient Proportion of components, except active pharmaceutical ingredient (%) 15 mg / g 50 mg / g 100 mg / g Capriol 90 Labrasol ALF Kolliphor EL TPGS Ethanol Self-emulsifying composition no. 85 8 78 45 45 10 86 9 28 45 45 10 87 10 29 10 80 10 11 23 45 45 10 12 24 40 40 10 10 13 25 30 30 30 10 Petition 870250090533, dated 03 / 10 / 2025, pages 45 / 60 / 41 14 26 22.5 22.5 45 10 15 27 10 10 70 10 (Production Example 2) Preparation of Comparative Example Compositions

[0098] Polyethylene glycol 400 was weighed in a quantity of 1 g, and the active pharmaceutical ingredient was added to it at a specified concentration, followed by treatment using an ultrasonic homogenizer at 50 °C to prepare PEG solutions with active pharmaceutical ingredient concentrations of 15 mg / g (PEG solution 1), 50 mg / g (PEG solution 2), and 100 mg / g (PEG solution 3). Furthermore, to 1 g of 0.5% aqueous methylcellulose solution prepared by adding and dissolving 125 mg of methylcellulose in 400 to 25 mL of purified water, the active pharmaceutical ingredient was added at a specified concentration, followed by treatment using an ultrasonic homogenizer at 50 °C to prepare MC solutions with an active pharmaceutical ingredient concentration of 15 mg / g (MC solution 1), an active pharmaceutical ingredient concentration of 50 mg / g (MC solution 2), and an active pharmaceutical ingredient concentration of 100 mg / g (MC solution 3). (Assessment 1-1) Dissolution test: Tube method

[0099] To 1.5 mL of an aqueous HCl / saline solution adjusted to pH 2.0, 1.0 mL of a 0.5% aqueous methylcellulose solution was added, followed by stirring at 37°C and 90 rpm to obtain a test liquid. To this test liquid, 100 mg of the self-emulsifying composition 1 to 84 prepared in Production Example 1, of the PEG 2 or 3 solution prepared in Production Example 2, or of the MC 2 solution were added as a test sample and mixed by inversion, followed by stirring at 37°C and 90 rpm. Then, 500 μL of the test liquid were collected 15 minutes after the addition of the test sample, and the solution thus collected was promptly filtered using a filtration flask integrated with a filter (Mini-UniPrep, pore size 45 μm) and centrifuged to obtain a supernatant. At 100 Petition 870250090533, dated 03 / 10 / 2025, page 46 / 60 / 41 μL of the supernatant, 100 μL of acetonitrile and 600 μL of a liquid water / acetonitrile mixture (1:1) were added to obtain a sample from the stomach stage (pH 2.4). After collecting the sample from the stomach stage, 7.5 mL of FaSSIF, which had been previously heated to 37°C, followed by stirring at 37°C and 90 rpm, were added. Then, 500 μL of the test liquid were collected 30 minutes after, or 30 minutes after, 60 minutes after, 90 minutes after, and 120 minutes after the addition of FaSSIF. The solution thus collected was immediately filtered using the filtration flask integrated into the filter (Mini-UniPrep, pore size 45 μm) and centrifuged to obtain a supernatant. To 200 μL of the supernatant, 200 μL of acetonitrile were added to obtain a sample of the small intestine stage (pH 6.4).Each sample was analyzed by high-performance liquid chromatography to measure the rate of drug dissolution in the stomach or small intestine. The analytical conditions for high-performance liquid chromatography were as follows. <hplc>

[00100] Detector: Ultraviolet absorptiometer (measurement wavelength: 264 nm)

[00101] Column: Stainless steel tube with an internal diameter of 3.0 mm and a length of 150 mm filled with octadecylsilyl silica gel for liquid chromatography with a particle size of 2.7 μm.

[00102] Column temperature: Constant temperature around 30°C

[00103] Flow rate: 0.5 mL / min

[00104] Area measurement range: 6 minutes after the sample has been injected

[00105] Mobile phase: 25 mM ammonium acetate solution (pH 5.0) / acetonitrile liquid mixture (13:12)

[00106] Dissolution rates at pH 2.4 or pH 6.4 relating to Petition 870250090533, dated 03 / 10 / 2025, page. The respective self-emulsifying compositions 1 to 84 are shown in Tables 9 to 15. Furthermore, numerical values ​​(tube method AUC0-2.25) of the AUC of the curves obtained by plotting time (0 to 2.25 hours) on the horizontal axis and dissolution rates on the vertical axis, and logarithmic values ​​(tube method Log AUC0-2.25) for self-emulsifying compositions 1 to 38 are shown in Tables 9 to 12. Additionally, the dissolution rates at pH 2.4 or pH 6.4, as well as the numerical values ​​(tube method AUC0-2.25) of the AUC of the curves obtained by plotting time (0 to 2.25 hours) on the horizontal axis and dissolution rates on the vertical axis, and the logarithmic value (tube method Log AUC0-2.25) for the respective self-emulsifying compositions 1 to 84 are shown in Tables 9 to 15. The respective PEG 2 solution, PEG 3 solution, and MC 2 solution are shown in Table 16. Table 9 Dissolution rate (pH 2.4) 10.6 42.0 62.1 6.4 82.7 60.1 0.6 2.8 84.0 59.7 Dissolution rate (pH 6.4) 43.0 7.5 6.8 36.7 81.1 87.6 72.2 8.0 85.4 81.6 Tube method AUC0-2.25 406.4 367.2 518.0 323.3 1219.9 1100.8 534.1 79.9 1258.9 1048.3 Log of tube method (AUC0-2.25) 6.0 5.9 6.3 5.8 7.1 7.0 6.3 4.4 7.1 7.0 Table 10 Dissolution rate (pH 2.4) 42.0 97.9 85.0 80.0 57.1 20.9 20.9 1.1 29.1 50.3 19.3 6.8 Dissolution rate (pH 6.4) 68.9 90.0 80.5 91.9 69.9 34.2 56.9 78.1 79.6 101.6 96.2 30.9 Tube method AUCo-2.25 771.1 1392.0 1222.1 1260.9 938.3 430.3 576.7 573.7 810.9 1126, 8 745.1 250.3 Tube Method Log(AUCo-2.25) 6.6 7.2 7.1 7.1 6.8 6.1 6.4 6.4 6.7 7.0 6.6 5.5 Table 11 Dissolution rate (pH 2.4) 17.0 49.8 32.0 28.2 27.2 56.8 31.5 59.8 62.8 9.2 12.1 35.2 Dissolution rate (pH 6.4) 30.2 43.8 42.1 48.4 57.5 49.9 58.4 44.7 46.8 34.1 38.6 33.6 Tube method AUCo-2.25 705.5 1387.5 1100.8 1137.2 1259.1 1583.4 1328. 2 1540, 8 1622, 3 642,9 757,2 1016, 1 Petition 870250090533, dated 03 / 10 / 2025, pages 48 / 60 / 41 Tube Method Log(AUCo-2.2s) 6.6 7.2 7.0 7.0 7.1 7.4 7.2 7.3 7.4 6.5 6.6 6.9 Table 12 Dissolution rate (pH 2.4) 0.5 11.4 9.4 13.4 1.0 0.8 1.1 0.9 2.1 2.1 41.3 45.0 Dissolution rate (pH 6.4) 41.1 21.4 19.4 25.4 16.2 6.3 15.1 6.8 17.9 21.3 52.9 53.6 Tube method AUC0-2.25 583.5 486.4 424.2 575.5 Log of tube method (AUC0-2.25) 6.4 6.2 6.1 6.4 Table 13 Dissolution rate (pH 2.4) 4.1 13.1 15.3 2.9 8.3 5.1 15.6 29.1 28.9 27.6 1.3 18.5 Dissolution rate (pH 6.4) 30.7 18.1 32.7 21.6 44.6 41.8 44.6 49.6 46.4 48.3 22.0 33.9 Table 14 Dissolution rate (pH 2.4) 6.8 21.7 7.8 28.8 42.8 32.6 22.0 3.0 15.4 20.8 26.9 19.1 Dissolution rate (pH 6.4) 37.2 59.2 43.6 41.9 54.2 46.2 44.6 22.5 32.0 36.8 47.4 43.6 Table 15 Dissolution rate (pH 2.4) 13.5 1.2 1.1 12.5 10.0 1.1 1.1 1.0 7.5 1.1 1.7 4.3 25.3 5.8 Dissolution rate (pH 6.4) 40.0 4.8 4.8 29.1 35.1 11.7 23.9 8.8 33.7 11.1 27.4 26.2 42.7 25.8 Table 16 PEG 2 Solution PEG 3 Solution MC 2 Solution Dissolution Rate (pH 2.4) 1.0 0.6 0.7 Dissolution Rate (pH 6.4) 21.8 12.7 20.5 Tube Method AUC0-2.25 165.8 199.7 156.4 Log of Tube Method (AUC0-2.25) 5.1 5.3 5.1 (Assessment 1-2) Dissolution test: Tube method

[00107] For self-emulsifying compositions 85 to 87 and a self-emulsifying composition (hereinafter referred to as a composition) Petition 870250090533, dated 03 / 10 / 2025, pp. 49 / 60 / 41. Self-emulsifying composition 88) prepared in the same manner as in self-emulsifying composition 30, except that 10% by mass of the active pharmaceutical ingredient, 11% by mass of Capriol 90, 77.2% by mass of Kolliphor EL, and 1.8% by mass of ethanol were contained, as well as MC solution 1 and MC solution 3 prepared in Production Example 2, the above dissolution test was conducted to measure the dissolution rates, and numerical values ​​(AUCo-2.25 of the tube method) of AUC and logarithmic values ​​(AUCo-2.25 of the tube method) thereof were calculated. The results are shown in Table 17. Table 17 Solution MC 1 Solution MC 3 85 86 87 88 Dissolution rate (pH 2.4) 0.9 0.1 17.7 69.4 3.8 31.4 Dissolution rate (pH 6.4) 40.0 8.4 15.4 92.2 68.3 53.3 Tube method AUCo-2.25 85.7 125.9 80.7 356.8 161.3 1245.0 Log of tube method (AUCo-2.25) 4.5 4.8 4.4 5.9 5.1 7.1 (Assessment 2-1) Assessment of blood plasma concentration 1 through the PO / PK experiment using rats

[00108] Each of the self-emulsifying compositions 85 to 87 was administered orally to each group of 3 male rats (Crl:CD(SD)) under fasting conditions, and the transition of the blood plasma concentration of the active metabolite of the active pharmaceutical ingredient was evaluated. Note that the fasting conditions were such that fasting was initiated approximately 15 hours or more before administration. Each animal was administered the self-emulsifying composition in an amount equivalent to 3 mg / kg of the active pharmaceutical ingredient. Blood was collected from the subclavian vein 0.25 hours, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 24 hours after administration, and blood plasma was collected by centrifugation. After a deproteinization treatment was conducted on blood plasma using acetonitrile, the concentration of the active metabolite in the blood plasma was measured using LC-MS / MS (API4000, manufactured Petition 870250090533, dated 03 / 10 / 2025, pp. 50 / 60 / 41 by AB SCIEX). Furthermore, as a control group, test animals were used to which the PEG 1 solution or the MC 1 solution prepared in Production Example 2 was administered. Tmax, Cmax and AUC of the concentration of the active metabolite in the blood plasma thus obtained are shown in Table 18. Table 18 Tmax (h) Cmax (ng / mL) AUC (h*ng / mL) PEG Solution 1 2.00 209 896 MC Solution 1 0.25 129 643 85 4.67 91.5 679 86 4.67 276 1645 87 3.33 242 1515 (Assessment 2-2) Assessment of blood plasma concentration 2 using the PO / PK experiment in rats

[00109] The transition of the total concentration of the active pharmaceutical ingredient and its active metabolite in blood plasma was evaluated in the same manner as in Evaluation 2-1, except that the self-emulsifying composition 28 or 29 in an amount equivalent to 100 mg / kg or 300 mg / kg of the active pharmaceutical ingredient was administered to each animal. In addition, as a control group, test animals were used to which the PEG 3 solution prepared in Production Example 2 was administered. The Cmax and AUC of the concentration of the active pharmaceutical ingredient and the active metabolite in blood plasma obtained in the case where the dosage was 100 mg / kg are shown in Table 19. In addition, the Cmax and AUC of the concentration of the active pharmaceutical ingredient and the active metabolite in blood plasma obtained in the case where the dosage was 300 mg / kg are shown in Table 20. Table 19 Cmax (ng / mL) AUC (h*ng / mL) PEG-3 Solution 1731±557 12052±2958 28 5840±2131 30342±8004 Petition 870250090533, dated 03 / 10 / 2025, pages 51 / 60 / 41 19224±5297 82017±26354 Table 20 Cmax (ng / mL) AUC (h*ng / mL) PEG-3 Solution 2943±1301 24041±9053 28 8725±1880 44461±5071 29 30875±13990 122348±43087 (Assessment 3) Evaluation of blood plasma concentration through the PO / PK experiment in dogs

[00110] Each of the self-emulsifying compositions 28 and 88 prepared in Production Example 1 was administered orally to 3 fasted male beagles (10 to 15 months of age), and the transition of the blood plasma concentration of the active pharmaceutical ingredient and the active metabolite was evaluated. Note that the fasting conditions were such that fasting was initiated 16 hours or more before administration. Each animal was given a gelatin capsule filled with the self-emulsifying composition in an amount equivalent to 100 mg / kg of the active ingredient and administered. Blood was collected from the cephalic vein 0.25 hours, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 24 hours after administration, and blood plasma was collected and treated. The total concentration of the active pharmaceutical ingredient and the active metabolite in blood plasma was measured using LC-MS / MS (API4000, manufactured by AB SCIEX).In addition, as a control group, test animals were used to which the PEG 3 solution prepared in Production Example 2 was administered. Tmax, Cmax and AUC of the concentration of the active pharmaceutical ingredient and the active metabolite in the blood plasma thus obtained are shown in Table 21. Table 21 Tmax (h) Cmax (nmol / l) AUC (h*nmol / L) PEG Solution 3 1 1924 8593 28 0.67 5050 21852 88 1.67 6671 26274 (Assessment 4) Correlation of the tube method and the PO / PK experiment Petition 870250090533, dated 03 / 10 / 2025, pages 52 / 60 / 41

[00111] Results obtained by plotting the logarithmic values ​​(tube method Log AUC0-2.25) of the AUC in the tube method obtained in Assessment 1 on the horizontal axis and the logarithmic values ​​(rat PO / PK Log AUC) of the blood plasma concentration AUC obtained in Assessment 2 on the vertical axis are shown in Fig. 1. Furthermore, the results obtained by plotting the logarithmic values ​​(Tube method Log AUC0-2.25) of the AUC in the tube method obtained in Assessment 1 on the horizontal axis and the dissolution rates (%) at pH 2.4 or pH 6.4 on the vertical axis are shown in Fig. 2 or Fig. 3. In addition, the respective correlation coefficients in Fig. 1 to Fig. 3 are shown in Table 22. The AUC0-2.25 of the tube method and the AUC of rat PO / PK have a strong positive correlation, and AUC0-2.25 The tube method and the dissolution rates at pH 2.4 and pH 6.4 have a positive correlation.It is possible to estimate the pharmacokinetics (AUC) in the in vivo evaluation from the results of AUC0-2.25 from the tube method or the dissolution rate at pH 2.4 or pH 6.4. Table 22 Correlation coefficient Log tube method (AUCo-2.25) vs Log PO / PK of rat (AUC) 0.961 Dissolution rate (pH 2.4) vs tube method Log (AUCo-2.25) 0.708 Dissolution rate (pH 6.4) vs tube method Log (AUCo-2.25) 0.640

[00112] The self-emulsifying composition of the present disclosure may improve the absorption capacity of the sulfonamide derivative represented by formula (1) after oral administration. Petition 870250090533, dated 03 / 10 / 2025, pp. 53 / 60< / hplc>

Claims

1 / 3 CLAIMS 1. Self-emulsifying composition, characterized in that it comprises: a sulfonamide derivative represented by the following formula (1), a pharmaceutically acceptable salt thereof, or an active metabolite thereof; and at least two solubilizers 2. Self-emulsifying composition according to claim 1, characterized in that at least two solubilizers comprise at least one surfactant and at least one auxiliary surfactant.

3. Self-emulsifying composition according to claim 1, characterized in that the solubilizers comprise at least two selected from a cyclodextrin or a derivative thereof, bile acid or a derivative thereof, a fatty alcohol, a fatty acid or derivatives thereof, and a tocopherol derivative.

4. Self-emulsifying composition according to claim 2, characterized in that the surfactant comprises at least one selected from the group consisting of polyglyceryl-2 dioleate, polyglyceryl-3 dioleate, polyglyceryl-10 trioleate, propylene glycol monolaurate, propylene glycol monocaprylate, glyceryl monocaprylate, glyceryl monolaurate, glyceryl dilaurate and glyceryl monolinoleate. Petition 870250090533, dated 03 / 10 / 2025, page 54 / 60 2 / 3 5. Self-emulsifying composition according to claim 2, characterized in that the auxiliary surfactant comprises at least one selected from the group consisting of castor oil polyoxyl 40, castor oil polyoxyl 35, PEG-25 trioleate, PEG-60 corn glycerides, PEG-60 almond oil, PEG-40 palm kernel oil, PEG-50 castor oil, PEG-50 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-8 caprylic / capric glycerides, lauroyl polyoxyl-32 glycerides, linoleoyl polyoxyl-6 glycerides, oleoyl polyoxyl-6 glycerides, stearoyl polyoxyl-32 glycerides, PEG-6 caprylic / capric glycerides, monooleate of polyglyceryl-10, polyglyceryl-10 laurate, polyglyceryl-15 hydroxystearate, PEG-400 α-tocopherol succinate, PEG-1000 α-tocopherol succinate, PEG-1000 dl-α-tocopherol succinate, and PEG-1000 d-tocopherol succinate.

6. Self-emulsifying composition according to any one of claims 2, 4 and 5, characterized in that the surfactant content is 0.1 times or more in relation to the % by mass of the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof, and the auxiliary surfactant content is 10 times or less in relation to the sulfonamide derivative represented by formula (1) or a pharmaceutically acceptable salt thereof.

7. Self-emulsifying composition according to any one of claims 2, 4 and 5, characterized in that the ratio of surfactant to auxiliary surfactant is from 1:1 to 8:

1.

8. Self-emulsifying composition according to claim 2 or 4, characterized in that the surfactant comprises propylene glycol monocaprylate.

9. Self-emulsifying composition according to claim 2 or 5, characterized in that the auxiliary surfactant Petition 870250090533, dated 03 / 10 / 2025, page 55 / 60 3 / 3 comprises polyoxyl 40 castor oil, polyoxyl 35 castor oil or polyoxyethylene castor oil.

10. Self-emulsifying composition according to claim 1 or 2, characterized in that it further comprises a co-solvent.

11. Self-emulsifying drug delivery system in a formulation form suitable for oral administration, characterized in that it comprises the self-emulsifying composition according to claim 1 or 2.

12. Self-emulsifying drug delivery system according to claim 11, characterized in that the formulation is a capsule. Petition 870250090533, dated 03 / 10 / 2025, pp. 56 / 60

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