Pharmaceutical composition containing trisulfide compound

Abstract

Disclosed is a pharmaceutical composition containing a specific trisulfide compound and a pharmaceutically acceptable carrier, in which the pharmaceutically acceptable carrier is at least one selected from the group consisting of silica gel-based carriers and saccharides.

Description

Technical Field

[0001] This invention relates to pharmaceutical compositions containing trisulfide compounds. Background Technology

[0002] Compounds containing a covalent structure formed by three consecutive sulfur atoms are called trisulfide compounds. Trisulfide compounds possess redox capabilities depending on the valence of the sulfur atoms that constitute them, and therefore are expected to have various physiological activities. For example, Non-Patent Literature 1 describes the reduction of neurodegeneration in a mouse model of Parkinson's disease by administration of polysulfides.

[0003] Patent Document 1 discloses panthionylamine trisulfide as a trisulfide compound. Patent Document 2 discloses trisulfide compounds and their inclusion compounds. Patent Document 3 discloses a method for manufacturing glutathione trisulfide as a trisulfide compound.

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: International Publication No. 2022 / 045052

[0007] Patent Document 2: International Publication No. 2022 / 045212

[0008] Patent Document 3: International Publication No. 2021 / 200487

[0009] Non-patent literature

[0010] Non-patent document 1: Fumiaki Nagashima et al., "Sulfide: quinone oxidoreductaseameliorates neurodegeneration in a murine model of Parkinson's disease", Redox Biology, 59:102562 (2023). Summary of the Invention

[0011] The problem that the invention aims to solve

[0012] In pharmaceutical compositions, the storage stability of the active ingredient can affect the amount of active ingredient administered to a subject after the composition is manufactured, thus affecting the therapeutic effect of the pharmaceutical composition. For example, if the active ingredient has high hygroscopicity (deliquescence), in a pharmaceutical composition where its hygroscopicity has not been improved, the active ingredient will absorb moisture and decompose during storage, resulting in a reduction in the effective concentration of the active ingredient in the administered subject.

[0013] Furthermore, in pharmaceutical compositions, ease of handling, such as fluidity, significantly impacts the convenience for patients to take the composition and the efficiency of dispensing it into appropriate dosages. Particularly when the fluidity of the pharmaceutical composition is low, it becomes difficult to ingest, dispense, or weigh accurately, potentially leading to unwanted dosages or loss of the composition due to adhesion to equipment.

[0014] The object of this invention is to provide a pharmaceutical composition containing a trisulfide compound.

[0015] Methods for solving problems

[0016] The inventors have discovered that pharmaceutical compositions containing trisulfide compounds and specific pharmaceutically acceptable carriers exhibit excellent storage stability and good handling properties.

[0017] This invention relates, for example, to the following:

[0018] [1] A pharmaceutical composition comprising a trisulfide compound and a pharmaceutically acceptable carrier, wherein the trisulfide compound is at least one selected from the group consisting of panthioethylamine trisulfide or a pharmaceutically acceptable salt thereof, a compound or a pharmaceutically acceptable salt of formula (1), and glutathione trisulfide or a pharmaceutically acceptable salt thereof.

[0019] (In the formula, X represents -OR) 1 or -NR 2 R 3 R 1 R represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. 2 and R 3 Each of the above-mentioned alkyl groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups.

[0020] The pharmaceutically acceptable carriers mentioned above are selected from at least one of the groups consisting of silica-based carriers and sugars.

[0021] [2] The pharmaceutical composition according to [1], wherein X in the above formula (1) is -OH.

[0022] [3] The pharmaceutical composition according to [1] or [2], wherein the trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof.

[0023] [4] The pharmaceutical composition according to any one of [1] to [3], wherein the pharmaceutically acceptable carrier is a silica gel carrier.

[0024] [5] The pharmaceutical composition according to any one of [1] to [4], wherein the trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is a silica gel carrier.

[0025] [6] The pharmaceutical composition according to any one of [1] to [5], wherein the above-mentioned silica gel carrier is a hydrophilic silica gel carrier.

[0026] [7] The pharmaceutical composition according to any one of [1] to [5], wherein the above-mentioned silica gel carrier is a hydrophobic silica gel carrier.

[0027] [8] The pharmaceutical composition according to any one of [1] to [7], wherein the mass ratio of the above-mentioned trisulfide compound in the pharmaceutical composition to the above-mentioned pharmaceutically acceptable carrier is 2:1 to 1:50.

[0028] [9] The pharmaceutical composition according to any one of [1] to [8], wherein the pharmaceutical composition is used for oral or transdermal administration.

[0029]

[10] The pharmaceutical composition according to any one of [1] to [9], wherein the pharmaceutical composition is a tablet, capsule, granule, powder, ointment, plaster or gel.

[0030]

[11] The pharmaceutical composition according to any one of [1] to

[10] , wherein the pharmaceutical composition is a tablet, capsule, granule or powder.

[0031]

[12] The pharmaceutical composition according to [1] wherein the pharmaceutically acceptable carrier is a sugar.

[0032]

[13] The pharmaceutical composition according to [1] or

[12] , wherein the pharmaceutically acceptable carrier is lactose.

[0033]

[14] The pharmaceutical composition according to [1],

[12] or

[13] , wherein the trisulfide compound is panthioethylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is lactose.

[0034]

[15] The pharmaceutical composition according to any one of claims [1] and

[12] to

[14] , wherein the mass ratio of the above-mentioned trisulfide compound in the pharmaceutical composition to the above-mentioned pharmaceutically acceptable carrier is 1:1 to 1:20.

[0035]

[16] The pharmaceutical composition according to any one of [1] and

[12] to

[15] , wherein the pharmaceutical composition is used for oral administration, pulmonary administration, nasal administration, oral administration, rectal administration or vaginal administration.

[0036]

[17] The pharmaceutical composition according to any one of [1] and

[12] to

[16] , wherein the pharmaceutical composition is in the form of tablets, capsules, granules, powders, inhaled powders, nasal powders, sublingual tablets, tablets, drops, suppositories or vaginal suppositories.

[0037]

[18] The pharmaceutical composition according to any one of [1] and

[12] to

[17] , wherein the pharmaceutical composition is a tablet, capsule, granule, powder, inhaled powder or nasal powder.

[0038]

[19] The pharmaceutical composition according to any one of [1] to

[18] is a carrier adsorption composition.

[0039]

[20] The pharmaceutical composition according to any one of [1] to

[19] is in the form of a powder.

[0040]

[21] The pharmaceutical composition according to any one of [1] to

[20] has an increase in mass of less than 2.0% when it is left to stand in air at a temperature of 25 ± 1.5 °C and a relative humidity of 43.0 ± 3.5% for 240 hours.

[0041]

[22] The pharmaceutical composition according to any one of [1] to

[21] , wherein the mass ratio of the above-mentioned trisulfide compound to the above-mentioned pharmaceutically acceptable carrier in the pharmaceutical composition is a mass ratio in which the mass increase after standing in air at a temperature of 25 ± 1.5 °C and a relative humidity of 43.0 ± 3.5% for 240 hours reaches 2.0% or less.

[0042]

[23] The pharmaceutical composition according to any one of [1] to

[22] has an increase in mass of 6.0% or less when it is left to stand in air at a temperature of 25 ± 1.5 °C and a relative humidity of 59.0 ± 5.5% for 240 hours.

[0043]

[24] The pharmaceutical composition according to any one of [1] to

[23] , wherein the mass ratio of the above-mentioned trisulfide compound to the above-mentioned pharmaceutically acceptable carrier in the pharmaceutical composition is a mass ratio in which the mass increase reaches 6.0% or less when the composition is left to stand in air at a temperature of 25 ± 1.5 °C and a relative humidity of 59.0 ± 5.5% for 240 hours.

[0044]

[25] The use or application of a pharmaceutically acceptable carrier in improving the preservation stability and ease of handling of a trisulfide compound in a pharmaceutical composition, wherein the trisulfide compound is at least one selected from the group consisting of panthioethylamine trisulfide or a pharmaceutically acceptable salt thereof, a compound or a pharmaceutically acceptable salt of formula (1), and glutathione trisulfide or a pharmaceutically acceptable salt thereof.

[0045] (In the formula, X represents -OR) 1 or -NR 2 R 3 R 1 R represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. 2 and R 3 Each of the above-mentioned alkyl groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups.

[0046] The pharmaceutically acceptable carriers mentioned above are selected from at least one of the groups consisting of silica-based carriers and sugars.

[0047]

[26] The use or application described in

[25] is the use or application in inhibiting the hygroscopicity of trisulfide compounds in a pharmaceutical composition and improving flowability.

[0048]

[27] A method for improving the storage stability and ease of handling of the above-mentioned trisulfide compound in a pharmaceutical composition, comprising combining a trisulfide compound and a pharmaceutically acceptable carrier, wherein the trisulfide compound is at least one selected from the group consisting of panthioethylamine trisulfide or a pharmaceutically acceptable salt thereof, a compound or a pharmaceutically acceptable salt of formula (1), and glutathione trisulfide or a pharmaceutically acceptable salt thereof.

[0049] (In the formula, X represents -OR) 1 or -NR 2 R 3 R 1 R represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. 2 and R 3 Each of the above-mentioned alkyl groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups.

[0050] The pharmaceutically acceptable carriers mentioned above are selected from at least one of the groups consisting of silica-based carriers and sugars.

[0051]

[28] The method according to

[27] is a method for inhibiting the hygroscopicity of trisulfide compounds in a pharmaceutical composition and improving flowability.

[0052]

[29] The use or application as described in

[25] or

[26] , or the method as described in

[27] or

[28] , wherein the trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof.

[0053]

[30] The use or application according to

[25] ,

[26] or

[29] , or the method according to

[27] ,

[28] or

[29] , wherein the pharmaceutically acceptable carrier is a silica gel carrier, comprising making the mass ratio of the trisulfide compound in the pharmaceutical composition to the pharmaceutically acceptable carrier 2:1 to 1:50.

[0054]

[31] The use or application according to

[25] ,

[26] or

[29] , or the method according to

[27] ,

[28] or

[29] , wherein the pharmaceutically acceptable carrier is lactose, comprising making the mass ratio of the trisulfide compound in the pharmaceutical composition to the pharmaceutically acceptable carrier 1:1 to 1:20.

[0055]

[32] The use or application according to any one of

[25] ,

[26] and

[29] to

[31] , or the method according to any one of

[27] to

[31] , wherein the above-mentioned pharmaceutical composition is a carrier adsorption composition.

[0056]

[33] The use or application according to any one of

[25] ,

[26] and

[29] to

[32] , or the method according to any one of

[27] to

[32] , wherein the above pharmaceutical composition is in powder form.

[0057]

[34] The use or application according to any one of

[25] ,

[26] and

[29] to

[33] , or the method according to any one of

[27] to

[33] , wherein the increase in mass of the above pharmaceutical composition when it is left to stand in air at a temperature of 25 ± 1.5 °C and a relative humidity of 43.0 ± 3.5% for 240 hours is less than 2.0%.

[0058]

[35] The use or application according to any one of

[25] ,

[26] and

[29] to

[34] , or the method according to any one of

[27] to

[34] , wherein the method comprises making the mass ratio of the above-mentioned trisulfide compound in the above-mentioned pharmaceutical composition to the above-mentioned pharmaceutically acceptable carrier such that the mass increase after standing in air at a temperature of 25 ± 1.5 °C and a relative humidity of 43.0 ± 3.5% for 240 hours reaches a mass ratio of 2.0% or less.

[0059]

[36] The use or application according to any one of

[25] ,

[26] and

[29] to

[35] , or the method according to any one of

[27] to

[35] , wherein the increase in mass of the above pharmaceutical composition is 6.0% when it is left to stand in air at a temperature of 25 ± 1.5 °C and a relative humidity of 59.0 ± 5.5% for 240 hours.

[0060]

[37] The use or application according to any one of

[25] ,

[26] and

[29] to

[36] , or the method according to any one of

[27] to

[36] , wherein the method comprises making the mass ratio of the above-mentioned trisulfide compound in the above-mentioned pharmaceutical composition to the above-mentioned pharmaceutically acceptable carrier such that the mass increase after standing in air at a temperature of 25 ± 1.5 °C and a relative humidity of 59.0 ± 5.5% for 240 hours reaches a mass ratio of 6.0% or less.

[0061] Invention Effects

[0062] According to the present invention, pharmaceutical compositions containing trisulfide compounds can be provided. According to the present invention, pharmaceutical compositions containing trisulfide compounds and pharmaceutically acceptable carriers can be provided.

[0063] According to the present invention, a pharmaceutical composition containing a trisulfide compound that exhibits excellent storage stability and ease of handling can be provided. According to the present invention, a pharmaceutical composition containing a trisulfide compound that exhibits excellent storage stability (e.g., deliquility) and ease of handling even without coating to improve moisture resistance and flowability can be provided. Attached Figure Description

[0064] Figure 1 This is a graph showing the results of the moisture absorption test of the pharmaceutical composition containing PTN-SSS under the condition of a relative humidity of about 20% in Test Example 1.

[0065] Figure 2 This is a graph showing the results of the moisture absorption test of the pharmaceutical composition containing PTN-SSS and the pharmaceutical composition containing PTN-SSS under the condition of a relative humidity of about 40% in Test Example 1.

[0066] Figure 3 This is a graph showing the results of the moisture absorption test of the pharmaceutical composition containing PTN-SSS and the pharmaceutical composition containing PTN-SSS under the condition of a relative humidity of about 60% in Test Example 1.

[0067] Figure 4 This is a graph showing the properties of the pharmaceutical composition containing PTN-SSS and the pharmaceutical composition containing PTN-SSS after a moisture absorption test under the condition of a relative humidity of about 60% in Test Example 1.

[0068] Figure 5 This is a graph showing the stability of the pharmaceutical composition containing PTN-SSS, the active pharmaceutical ingredient of PTN-SSS, and the aqueous solution of PTN-SSS in Test Example 2 under high temperature conditions of 40°C.

[0069] Figure 6 This is a graph showing the change over time of the peak area (%) of the PTN-SS source relative to the peak area of ​​the PTN-SSS source in Experimental Example 5 under the same conditions as in Experimental Example 2.

[0070] Figure 7 This is a graph showing the change over time of the peak area (%) of the PTN-SSSS source produced in Experiment 5 under the same conditions as in Experiment 2. Detailed Implementation

[0071] The following describes the methods for implementing the present invention, but the present invention is not limited to the following embodiments.

[0072] One embodiment of the present invention relates to a pharmaceutical composition comprising a trisulfide compound and a pharmaceutically acceptable carrier. One embodiment of the pharmaceutical composition of the present invention uses a trisulfide compound as the active ingredient. One embodiment of the pharmaceutical composition of the present invention contains a therapeutically effective amount of a trisulfide compound.

[0073] <Trisulfide compounds>

[0074] In one embodiment of the present invention, the trisulfide compound is at least one selected from the group consisting of panthioethylamine trisulfide or a pharmaceutically acceptable salt thereof, a compound of formula (1) (hereinafter also referred to as "compound (1)") or a pharmaceutically acceptable salt thereof, and glutathione trisulfide or a pharmaceutically acceptable salt thereof.

[0075] [In the formula, X represents -OR] 1 or -NR 2 R 3 R 1 R represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. 2 and R 3 Each of the above-mentioned alkyl groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups.

[0076] These trisulfide compounds may be contained in pharmaceutical compositions in forms other than free forms or pharmaceutically acceptable salts thereof, for example, in the form of their solvates (e.g., hydrates).

[0077] In this invention, pharmaceutically acceptable salts include, for example, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; salts with organic acids such as acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, lactic acid, stearic acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, and p-toluenesulfonic acid; salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; ammonium salts; and salts with amino acids such as arginine.

[0078] Panthionylamine trisulfide is represented by the following formula (2A). Panthionylamine trisulfide can be prepared, for example, according to the method described in Patent Document 1.

[0079]

[0080] Glutathione trisulfide is represented by the following formula (2). Glutathione trisulfide can be prepared, for example, according to the method described in Patent Document 3.

[0081]

[0082] As a pharmaceutically acceptable salt of glutathione trisulfide and panthioethylamine trisulfide, it is preferably an amino acid salt or an alkali metal salt, more preferably an arginine salt or a sodium salt. As a pharmaceutically acceptable salt of compound (1), it is preferably a salt with an alkali metal, more preferably a sodium salt.

[0083] Compound (1) can be prepared, for example, according to the method described in Patent Document 2.

[0084] In one embodiment, compound (1) is the compound shown in formula (3).

[0085]

[0086] [In the formula, R] 1 This refers to an alkyl group having 1 to 6 hydrogen atoms or carbon atoms.

[0087] R 1 For example, it can be a hydrogen atom, methyl, ethyl, propyl, butyl, pentyl, or hexyl. R is preferred. 1 If the atom is hydrogen, then the compound shown in formula (3) is the thioctic trisulfide shown in formula (4).

[0088]

[0089] In another embodiment, compound (1) is the compound shown in formula (5).

[0090]

[0091] [In the formula, R] 2 and R3 Each of the above-mentioned alkyl groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups.

[0092] R 1 and R 2 It can be an alkyl group such as hydrogen atom, methyl, ethyl, propyl, butyl, pentyl, or hexyl. These alkyl groups can have one or both of the following substituents: amino and carboxyl. R 1 and R 2 For example, it can be a group as shown in formula (6) (where, (representing a bonding bond). As a specific example of the compound shown in formula (5), examples can be given, such as: R 2 and R 3 Compounds consisting entirely of hydrogen atoms, R 2 It is a hydrogen atom and R 3 Compounds of the group shown in formula (6).

[0093]

[0094] In a preferred embodiment, the trisulfide compound of the present invention may be panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, compound (1) or a pharmaceutically acceptable salt thereof, or glutathione trisulfide or a pharmaceutically acceptable salt thereof; in a more preferred embodiment, it may be panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, or glutathione trisulfide or a pharmaceutically acceptable salt thereof; and in a particularly preferred embodiment, it may be panthionylamine trisulfide or a pharmaceutically acceptable salt thereof.

[0095] In one embodiment of the present invention, the pharmaceutically acceptable carrier is at least one selected from the group consisting of silica-based carriers and sugars.

[0096] The silica carrier used in the pharmaceutical composition of the present invention can be any carrier that is pharmaceutically acceptable. For example, the silica carrier of the present invention can be fumed silica or colloidal silica; in a preferred embodiment, it can be fumed silica.

[0097] As the silicone carrier of the present invention, it can be, for example, a hydrophobic (i.e., surface-treated) or hydrophilic (i.e., untreated) silicone carrier. When the silicone carrier of the present invention is hydrophobic, the surface treatment is not particularly limited as long as it is a surface treatment commonly performed by those skilled in the art. For example, it can be modified with dimethylsilyl, trimethylsilyl, octylsilyl, or dimethylpolysiloxane. In a preferred embodiment, it can be modified with dimethylsilyl, which can be implemented by surface treatment using dimethyldichlorosilane.

[0098] The specific surface area of ​​the fumed silica used as the silica carrier in the pharmaceutical composition of the present invention, based on the BET method (Brunauer, Emmett, and Teller methods), can be, for example, 30 to 1000 m². 2 / g, 45~660m 2 / g, 60~500m 2 / g or 90~330m 2 / g, or for example, 30–400m 2 / g, 45~260m 2 / g, 60~200m 2 / g or 90~130m 2 / g.

[0099] The pH of the fumed silica, which serves as the silica carrier of the pharmaceutical composition of the present invention, in a 4% aqueous dispersion can be, for example, 3.0–7.0, 3.3–6.5, 3.6–6.0, or 3.8–5.5.

[0100] The specific gravity of the fumed silica used as the silica carrier in the pharmaceutical composition of the present invention can be, for example, 10–250 g / L, 20–125 g / L, 25–100 g / L, or 40–60 g / L.

[0101] Examples of silica-based carriers used in the pharmaceutical compositions of the present invention include the AEROSIL (registered trademark) series (EVONIK), the SYLOID (registered trademark) series (GRACE), and the CAB-O-SIL (registered trademark) series (CABOT). In a preferred embodiment, the AEROSIL (registered trademark) series can be used; in a more preferred embodiment, AEROSIL (registered trademark) R972, AEROSIL (registered trademark) 300, or AEROSIL (registered trademark) 200 can be used; and in a particularly preferred embodiment, AEROSIL (registered trademark) R972 can be used. AEROSIL (registered trademark) R972 is a hydrophobic fumed silica surface-treated with dimethyldichlorosilane, with a specific surface area of ​​90–130 m² based on the BET method. 2 AEROSIL 300, a hydrophilic fumed silica, has a pH of 4.0–5.5 in a 4% aqueous dispersion and an apparent specific gravity of approximately 50 g / L. The pH is 4.0–5.5. 2 / g, the pH of the 4% aqueous dispersion is 3.8 to 4.3, and the apparent specific gravity is about 50 g / L.

[0102] The sugar used in the pharmaceutical composition of the present invention is not particularly limited as long as it is a pharmaceutically acceptable carrier. For example, it can be a monosaccharide, oligosaccharide, or polysaccharide. In a preferred embodiment, it can be a monosaccharide or oligosaccharide; in a more preferred embodiment, it can be a monosaccharide or disaccharide. In the present invention, oligosaccharides refer to sugars composed of glycosidic bonds of two or more but less than six monosaccharides (disaccharides to hexasaccharides), and polysaccharides refer to sugars composed of glycosidic bonds of seven or more monosaccharides.

[0103] The sugars involved in the pharmaceutical compositions of the present invention may have a molecular weight of less than 10,000, less than 3,000, less than 1,000, less than 500, or less than 350.

[0104] Examples of monosaccharides in the pharmaceutical compositions of the present invention include glucose, fructose, xylitol, D-sorbitol, and D-mannitol. Examples of oligosaccharides in the pharmaceutical compositions of the present invention include lactose, sucrose, maltose, trehalose, and cyclodextrin. Examples of polysaccharides in the pharmaceutical compositions of the present invention include starch, hydroxypropyl methylcellulose, and dextran. In one embodiment of the present invention, the sugars in the pharmaceutical compositions may be sugars other than cyclodextrin.

[0105] The sugar used in the pharmaceutical composition of the present invention may be, for example, lactose, glucose, sucrose, maltose, or trehalose. In a preferred embodiment, it may be lactose or sucrose, and in a more preferred embodiment, it may be lactose.

[0106] In one embodiment of the pharmaceutical composition of the present invention, the trisulfide compound may be panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier may be a silica gel carrier. In another embodiment of the pharmaceutical composition of the present invention, the trisulfide compound may be panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier may be a sugar.

[0107] In one embodiment of the present invention, the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition can be 2:1 to 1:50, 2:1 to 1:20, 2:1 to 1:9, 1.8:1 to 1:6, 1.6:1 to 1:4, 1.4:1 to 1:2, or 1.2:1 to 1:1.2. If the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier is within the above ranges, hygroscopicity in the pharmaceutical composition is suppressed, and operation becomes easier. The mass of the trisulfide compound in the above mass ratios can be the mass converted from free volume.

[0108] In a pharmaceutical composition according to one embodiment of the present invention, when the pharmaceutically acceptable carrier is a silica gel-based carrier, the mass ratio of the trisulfide compound to the silica gel-based carrier can be 2:1 to 1:50, 2:1 to 1:20, 2:1 to 1:9, 1.8:1 to 1:6, 1.6:1 to 1:4, 1.4:1 to 1:2, or 1.2:1 to 1:1.2. If the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier is within the above ranges, hygroscopicity in the pharmaceutical composition is suppressed, and operation becomes easier. The mass of the trisulfide compound in the above mass ratios can be the mass converted from free volume.

[0109] In a pharmaceutical composition according to one embodiment of the present invention, when the pharmaceutically acceptable carrier is a sugar, the mass ratio of the trisulfide compound to the sugar can be 1:1 to 1:20, 1:1 to 1:14, 1:1 to 1:9, 1:1 to 1:6, 1:1 to 1:4, 1:1 to 1:2, or 1:1 to 1:1.2. If the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier is within the above ranges, hygroscopicity in the pharmaceutical composition is significantly suppressed. The mass of the trisulfide compound in the above mass ratios can be the mass converted from free volume.

[0110] In addition to a trisulfide compound and a pharmaceutically acceptable carrier, the pharmaceutical composition of one embodiment of the present invention may also contain additives as other components. Examples of additives include: amino acids (L-arginine, etc.), water-soluble polymers (HES (hydroxyethyl starch), PVP (polyvinylpyrrolidone), etc.), nonionic surfactants (polysorbate, poloxamer, etc.) and other stabilizers, sodium chloride and other exudants, and glycine and sodium chloride and other excipients.

[0111] In one embodiment of the present invention, the dosage of the trisulfide compound in the pharmaceutical composition is preferably 0.5 to 800 mg per kg body weight per day (0.5 to 800 mg / kg / day), more preferably 1 to 400 mg / kg / day, and even more preferably 2 to 200 mg / kg / day.

[0112] The dosage of the pharmaceutical composition according to one embodiment of the present invention can be set to 1 to 8 times a day or 1 to 4 times a day. It is believed that setting the dosage in this way reduces the burden of medication on patients and improves medication adherence.

[0113] The pharmaceutical composition of one embodiment of the present invention can be used for oral, transdermal, pulmonary, ophthalmic, nasal, oral, rectal, or vaginal administration. In other words, the pharmaceutical composition of one embodiment of the present invention can be in a form suitable for oral, transdermal, pulmonary, ophthalmic, nasal, oral, rectal, or vaginal administration. In the pharmaceutical composition of one embodiment of the present invention, when the pharmaceutically acceptable carrier is a silica gel carrier, the pharmaceutical composition can be used for oral or transdermal administration, and in a preferred embodiment, it can be used for oral administration. In the pharmaceutical composition of one embodiment of the present invention, when the pharmaceutically acceptable carrier is a carbohydrate, the pharmaceutical composition can be used for oral, pulmonary, ophthalmic, nasal, oral, rectal, or vaginal administration, and in a preferred embodiment, it can be used for oral, pulmonary, nasal, or oral administration, and in a more preferred embodiment, it can be used for oral administration.

[0114] The pharmaceutical composition of one embodiment of the present invention may be in the form of tablets, capsules, granules, powders, ointments, patches, gels, inhaled powders, nasal powders, sublingual tablets, lozenges, drops, suppositories, or vaginal suppositories. In one embodiment of the pharmaceutical composition of the present invention, when the pharmaceutically acceptable carrier is a silicone-based carrier, the pharmaceutical composition may be in the form of tablets, capsules, granules, powders, ointments, patches, or gels, and in a preferred embodiment, it may be tablets, capsules, granules, or powders. In one embodiment of the pharmaceutical composition of the present invention, when the pharmaceutically acceptable carrier is a carbohydrate, the pharmaceutical composition may be in the form of tablets, capsules, granules, powders, inhaled powders, nasal powders, sublingual tablets, lozenges, drops, suppositories, or vaginal suppositories, and in a preferred embodiment, it may be tablets, capsules, granules, powders, inhaled powders, or nasal powders, and in a more preferred embodiment, it may be tablets, capsules, granules, or powders. In these cases, tablets, capsules, granules, or powders may be used for oral administration; ointments or patches may be used for transdermal administration; gels may be used for eye drops, nasal drops, oral administration, or vaginal administration; inhaled powders may be used for pulmonary administration; nasal powders may be used for nasal administration; sublingual tablets, lozenges, or drops may be used for oral administration; suppositories may be used for rectal administration; and vaginal suppositories may be used for vaginal administration.

[0115] One embodiment of the pharmaceutical composition of the present invention may be a carrier-adsorbed composition. That is, one embodiment of the pharmaceutical composition of the present invention may be a composition in which a trisulfide compound and additives as other components are adsorbed onto a pharmaceutically acceptable carrier. In the present invention, the carrier-adsorbed composition is distinguished from a solid dispersion using a polymer. One embodiment of the pharmaceutical composition of the present invention may be in powder form.

[0116] The pharmaceutical composition of one embodiment of the present invention inhibits hygroscopicity. In the present invention, inhibiting hygroscopicity can be, for example, defined as a mass increase of less than 2.0%, less than 1.5%, or less than 1.0% after standing for 240 hours in air at a temperature of 25±1.5°C and a relative humidity of 43.0±3.5%, or a mass ratio of the trisulfide compound in the pharmaceutical composition to a pharmaceutically acceptable carrier that achieves the aforementioned mass increase. In the present invention, inhibiting hygroscopicity can be, for example, defined as a mass increase of less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, or less than 20% of the mass increase of the active pharmaceutical ingredient containing the trisulfide compound in the pharmaceutical composition after standing under the same conditions, or a mass ratio of the trisulfide compound in the pharmaceutical composition to a pharmaceutically acceptable carrier that achieves the aforementioned mass increase. In this invention, suppressing hygroscopicity can be, for example, by an increase in mass of less than 6.0%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.0%, less than 2.0%, or less than 1.0% when the mixture is left to stand in air at a temperature of 25±1.5°C and a relative humidity of 59.0±5.5% for 240 hours. Alternatively, the mass ratio of the trisulfide compound in the pharmaceutical composition to a pharmaceutically acceptable carrier may be the same as the mass ratio that achieves the aforementioned increase in mass. In this invention, hygroscopic suppression can, for example, mean that the increase in mass after standing in air at a temperature of 25±1.5°C and a relative humidity of 59.0±5.5% for 240 hours is less than 90%, 80%, 70%, 60%, 50%, 40%, 30%, or 20% of the increase in mass of the active pharmaceutical ingredient containing the trisulfide compound in the pharmaceutical composition after standing under the same conditions, or the mass ratio of the trisulfide compound in the pharmaceutical composition to a pharmaceutically acceptable carrier reaches the aforementioned mass increase ratio. Furthermore, by further encapsulating or otherwise formulating the pharmaceutical composition with hygroscopic suppression by containing a carrier as described above for moisture protection purposes, formulations with even better moisture protection can be obtained.

[0117] The pharmaceutical composition of one embodiment of the present invention exhibits excellent storage stability. In the present invention, excellent storage stability of the pharmaceutical composition may, for example, mean that the aforementioned moisture absorption is inhibited in the pharmaceutical composition. Furthermore, excellent storage stability of the pharmaceutical composition in the present invention may, for example, mean that the proportion of trisulfide compound decomposition after standing in air at 40°C under light-protected conditions for 14 days is 18% or less, 15% or less, 10% or less, 5% or less, 4% or less, 3% or less, or 2% or less.

[0118] The pharmaceutical composition of one embodiment of the present invention exhibits excellent flowability. In the present invention, excellent flowability of the pharmaceutical composition can be, for example, defined as an angle of repose (static angle of repose) of 45° or less, 40° or less, 35° or less, 30° or less, or 25° or less. Furthermore, in the present invention, excellent flowability of the pharmaceutical composition can be, for example, defined as a compressibility of 25% or less, 20% or less, 15% or less, 13% or less, 10% or less, or 9% or less. This angle of repose can be, for example, defined according to "18th Revised Japanese Pharmacopoeia, Reference Information, Flowability of Powders". <g2-3-171>(The 18th edition of the Japanese Pharmacopoeia, reference information, fluidity of powders) <g2-3-171>The value was determined by the method described in ").

[0119] The pharmaceutical composition of one embodiment of the present invention exhibits excellent ease of handling (easy to operate). In the present invention, ease of handling of the pharmaceutical composition may refer, for example, to the aforementioned excellent flowability of the pharmaceutical composition. Furthermore, examples of ease of handling of the pharmaceutical composition in the present invention include: suppression of excessive viscosity and clumping, reduced adhesion to spatulas and dispensing machines, and reduced scattering caused by wind, etc.

[0120] Another aspect of the invention is the use or application of a pharmaceutically acceptable carrier in improving the storage stability of trisulfide compounds in a pharmaceutical composition and enhancing ease of handling. In one embodiment, the aforementioned use or application may be in inhibiting the hygroscopicity of trisulfide compounds in a pharmaceutical composition and improving flowability. As the trisulfide compound, pharmaceutically acceptable carrier, and pharmaceutical composition in these cases, the same substances as those in the pharmaceutical composition of one embodiment of the invention described above can be used.

[0121] Another aspect of the present invention is a method for improving the storage stability and ease of handling of a trisulfide compound in a pharmaceutical composition, comprising combining a trisulfide compound and a pharmaceutically acceptable carrier. In one embodiment, the method may be a method for inhibiting the hygroscopicity of the trisulfide compound in the pharmaceutical composition and improving its flowability. In one embodiment, the method improves the storage stability and ease of handling of the trisulfide compound in a pharmaceutical composition containing a trisulfide compound, wherein at least one carrier selected from the group consisting of silica gel carriers and sugars may be added to the pharmaceutical composition. As the trisulfide compound, the pharmaceutically acceptable carrier, and the pharmaceutical composition in these cases, the same substances as those in the pharmaceutical composition of one embodiment of the present invention described above can be used.

[0122] In one embodiment of these uses, applications, or methods, the pharmaceutically acceptable carrier is a silica gel carrier, comprising having the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition be 2:1 to 1:50, 2:1 to 1:20, 2:1 to 1:9, 1.8:1 to 1:6, 1.6:1 to 1:4, 1.4:1 to 1:2, or 1.2:1 to 1:1.2. If the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier is within the above ranges, hygroscopicity in the pharmaceutical composition is suppressed, and operation becomes easier. The mass of the trisulfide compound in the above mass ratio can be the mass converted from free volume.

[0123] In one embodiment of these uses, applications, or methods, the pharmaceutically acceptable carrier is lactose, comprising having the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition be 1:1 to 1:20, 1:1 to 1:14, 1:1 to 1:9, 1:1 to 1:6, 1:1 to 1:4, 1:1 to 1:2, or 1:1 to 1:1.2. If the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier is within the above ranges, hygroscopicity in the pharmaceutical composition is significantly inhibited. The mass of the trisulfide compound in the above mass ratio can be expressed as the mass of the free volume.

[0124] Example

[0125] The present invention will be described in more detail below using examples, but the present invention is not limited to the following examples.

[0126] In the following examples, panthionylamine trisulfide is also referred to as PTN-SSS. PTN-SS is a compound represented by the following structural formula.

[0127]

[0128] Additionally, in the following examples, panthionylamine tetrasulfide is also referred to as PTN-SSSS. PTN-SSSS is a compound formed by further inserting a sulfur atom in a straight chain at the trisulfide site of PTN-SSS, and is represented by the following structural formula.

[0129]

[0130] The PTN-SSS used in the following examples was prepared according to the method described in Patent Document 1.

[0131] <Preparation Example 1: Preparation of a composition containing PTN-SSS and a silica-based carrier>

[0132] Dissolve 1 g of PTN-SSS in 10 mL of methanol. Add AEROSIL 300 or AEROSIL R972 to the solution at a mass ratio of 2:1, 1:1, 1:4, or 1:9, and stir for 30 minutes. Then, remove the methanol by vacuum distillation and dry under reduced pressure.

[0133] <Preparation Example 2: Preparation of a composition containing PTN-SSS and sugars>

[0134] Dissolve 1 g of PTN-SSS in 10 mL of methanol, then add lactose to the solution to achieve a PTN-SSS to lactose mass ratio of 2:1, 1:1, 1:4, or 1:9, and stir for 30 minutes. Then, remove the methanol by vacuum distillation and dry under reduced pressure.

[0135] <Experimental Example 1: Hygroscopic Test of Compositions Containing PTN-SSS>

[0136] For PTN-SSS and the compositions prepared in Preparation Examples 1 and 2, storage stability (hygroscopicity, deliquescence) was evaluated based on mass changes under conditions of relative humidity of approximately 20%, 40%, and 60%. As an evaluation of hygroscopicity, the samples prepared in Preparation Examples 1 and 2 were stored in a desiccator where humidity was kept constant using the saturated salt method. Weights were measured from the start of storage until 72 hours, and the amount of moisture absorbed was calculated based on the weight change.

[0137] The results of mass changes under conditions of approximately 20% relative humidity (25.0 ± 2.5%, adjusted by the saturated salt method using a saturated aqueous solution of potassium acetate) are shown below. Figure 1 The results of mass changes under conditions of approximately 40% relative humidity (43.0 ± 3.5%, adjusted for humidity using a saturated salt method with a saturated potassium carbonate aqueous solution) are shown in the figure. Figure 2 The results of mass changes under conditions of approximately 60% relative humidity (59.0 ± 5.5%, adjusted for humidity using the saturated salt method with a saturated potassium iodide aqueous solution) are shown in the figure. Figure 3 In addition, photographs of each composition are shown 72 hours after the start of the experiment under conditions of approximately 60% relative humidity. Figure 4 In the middle. It should be noted that, Figure 4 The report also shows photographs taken before the start of the experiment and 24 and 72 hours after the start of the experiment, under a relative humidity of 60% as a control. According to... Figures 1-3 As a control, PTN-SSS showed a mass increase under relative humidity conditions of approximately 40% and 60%, and continued to absorb moisture after 10 days. Furthermore, PTN-SSS also exhibited deliquescence under relative humidity conditions of approximately 20%, failing to maintain a solid state. In contrast, compositions containing sugars (lactose) at a mass ratio of 1:1 or higher relative to PTN-SSS, and compositions containing silica gel carriers (AEROSIL 300, AEROSIL R972) at a mass ratio of 2:1 or higher relative to PTN-SSS, did not show the same mass increase as PTN-SSS under relative humidity conditions of approximately 40% and 60%, moisture absorption was suppressed, and the powder state was maintained even after 10 days. Specifically, under conditions of approximately 40% relative humidity, the mass increase of the composition after 10 days was suppressed to below 2.0%, and under conditions of approximately 60% relative humidity, the mass increase of the composition after 10 days was suppressed to below 6.0%, 5.0%, and 4.5%, respectively. These results indicate that compositions containing trisulfide compounds and sugars or silica gel carriers as pharmaceutically acceptable carriers exhibit excellent hygroscopicity and storage stability.

[0138] <Experimental Example 2: Stability Test of Compositions Containing PTN-SSS under High Temperature Conditions>

[0139] The stability of PTN-SSS (active drug substance), aqueous solution of PTN-SSS, composition containing PTN-SSS and silica gel, and compositions prepared in Preparation Examples 1 and 2 were tested under high temperature conditions. It should be noted that the aqueous solution of PTN-SSS simulates the hygroscopic properties of the PTN-SSS active drug substance, with PTN-SSS set at a high concentration (80%).

[0140] As the aqueous solution of PTN-SSS used in Example 2, 80% PTN-SSS was prepared by weighing 245 mg of PTN-SSS and adding 61 μL of purified water. Additionally, 50% PTN-SSS (silica gel) was prepared as follows: 1 g of PTN-SSS was dissolved in 10 mL of methanol, and the solution was added to silica gel (Kanto Chemical, silica gel 60N, spherical, neutral) at a mass ratio of 1:1. After stirring for 30 minutes, methanol was removed by vacuum distillation, and the solution was dried under reduced pressure to prepare 50% PTN-SSS (silica gel).

[0141] Weigh each sample into a brown 20 mL spiral-tube bottle and store it in a constant temperature incubator at 40°C. Take appropriate samples from the start of the stability test until 14 days, and determine the HPLC purity using HPLC. The HPLC analytical conditions are shown below.

[0142] Detector: Ultraviolet spectrophotometer (measurement wavelength: 220 nm)

[0143] Column: LiChrosorb RP-18 (Kanto Chemical, 4.0 × 250 mm, 5 μm)

[0144] Column temperature: a constant temperature around 40℃

[0145] Mobile phase A: Aqueous phosphoric acid solution (pH 3)

[0146] Mobile phase B: Methanol

[0147] Liquid delivery of the mobile phase: As shown in Table 1, the mixing ratio of mobile phase A and mobile phase B is changed to control the concentration gradient.

[0148] [Table 1]

[0149] Flow rate: 0.6 mL / min

[0150] Injection volume: 10 μL

[0151] The results are shown in Figure 5 In. Figure 5 In this context, 50% (lactose) indicates a composition with a PTN-SSS to lactose mass ratio of 1:1, 50% (AEROSIL) indicates a composition with a PTN-SSS to AEROSIL300 mass ratio of 1:1, 20% (lactose) indicates a composition with a PTN-SSS to lactose mass ratio of 1:4, and 20% (AEROSIL) indicates a composition with a PTN-SSS to AEROSIL300 mass ratio of 1:4. According to... Figure 5 In aqueous solutions of PTN-SSS, the PTN-SSS content decreased to below 85% after 14 days at 40°C. In contrast, no significant decrease in PTN-SSS content was observed in compositions containing PTN-SSS and pharmaceutically acceptable sugar or silica carriers. This indicates that compositions containing trisulfide compounds and pharmaceutically acceptable sugar or silica carriers are stable under high-temperature conditions and exhibit excellent storage stability.

[0152] <Experimental Example 3: Ease of Handling of Compositions Containing PTN-SSS>

[0153] For the results obtained in Experiment Example 1 Figure 4 The composition shown in the photograph 72 hours later, and with Figure 4 Similarly, after standing for 72 hours under conditions of relative humidity of approximately 20% or 40%, the properties of the powder and handling were visually confirmed.

[0154] The results under conditions of approximately 60% relative humidity (60%RH) are shown in Table 2. The results under conditions of approximately 40% relative humidity (40%RH) and approximately 20% relative humidity (20%RH) are shown in Table 3. In Tables 2 and 3, A indicates excellent handling, B indicates good handling, and C indicates less than good handling. Additionally, in Tables 2 and 3, 1) indicates no powdering and high viscosity; 2) indicates easy handling, but if it absorbs moisture, it forms lumps and adheres to the spatula, etc.; 3) indicates a large amount of carrier, making it slightly difficult to handle due to minor airborne particles. Based on the results in Tables 2 and 3, the compositions containing sugars at a mass ratio of 1:1 to 1:9 relative to PTN-SSS and the compositions containing silica gel carriers at a mass ratio of 2:1 to 1:9 relative to PTN-SSS are the compositions with better handling ease.

[0155] [Table 2]

[0156] [Table 3]

[0157] <Experimental Example 4: Flowability of Compositions Containing PTN-SSS>

[0158] The flowability of the compositions containing PTN-SSS and silica gel, as well as the compositions prepared in Preparation Examples 1 and 2, was evaluated.

[0159] Based on the 18th revised edition of the Japanese Pharmacopoeia, reference information, and powder flowability. <g2-3-171>The angle of repose and compressibility shall be determined according to the measurement method described in the document and the following scheme.

[0160] Determination of the angle of repose

[0161] 1. Place the funnel at a height of about 2cm above the bottom of the powder.

[0162] 2. Allow the powder to fall and measure the height of the resulting powder mound.

[0163] 3. Measure the length of the bottom surface.

[0164] 4. Calculate the angle of repose using the following formula.

[0165]

[0166] Determination of compressibility

[0167] 1. Gently add the powder into a 10mL graduated cylinder.

[0168] 2. Record the loose bulk density (V0).

[0169] 3. Tap the graduated cylinder until the volume no longer changes.

[0170] 4. Record the tap density (V) f ).

[0171] 5. Calculate the compressibility using the following formula.

[0172]

[0173] The results for compositions with a PTN-SSS to carrier (lactose, AEROSIL 300, AEROSIL R972) mass ratio of 1:1 to 1:9, as well as the angle of repose and compressibility of the carrier alone, are shown in Tables 4 and 5, respectively. The general flowability metrics relative to the angle of repose and compressibility, which serve as the benchmark for evaluating flowability in Tables 4 and 5, are shown in Table 6. In Tables 4 and 5, 1) indicates adhesion and cannot be measured. Furthermore, the composition with a PTN-SSS to silica mass ratio of 1:4 has an angle of repose of 23° and a compressibility of 8.5. Based on these results, compositions containing sugars at a mass ratio of 1:4 to 1:9 relative to PTN-SSS, and compositions containing silica-based carriers at a mass ratio of 1:1 to 1:9 relative to PTN-SSS, are compositions with excellent flowability.

[0174] [Table 4]

[0175] [Table 5]

[0176] [Table 6]

[0177] <Experimental Example 5: Inhibition Test of Variation Products of Compositions Containing PTN-SSS under High Temperature Conditions>

[0178] In the stability test under high temperature conditions in Example 2, the types and amounts of the variation products were analyzed by HPLC. The results showed that PTN-SS and PTN-SSSS, as variation products of PTN-SSS, were detected; however, no compounds resulting from the hydrolysis of the amide bond and the release of pantothenic acid were detected.

[0179] Figure 6 This is a graph showing the change over time of the peak area (%) of the PTN-SS source relative to the peak area of ​​the PTN-SS source under the same conditions as in Experimental Example 2. Figure 7 This is a graph showing the time-dependent change in the peak area (%) of the PTN-SSSS source relative to the peak area of ​​the PTN-SSS source, under the same conditions as in Experimental Example 2. According to... Figure 6 and Figure 7 In aqueous solutions of PTN-SSS, PTN-SS and PTN-SSSS were significantly generated over time. On the other hand, no significant generation of these modified products was found in compositions containing sugars or silica gels as pharmaceutically acceptable carriers.

[0180] It is known that in PTN-SS, compounds resulting from the hydrolysis of amide bonds and the release of pantothenic acid are produced as thermal decomposition products. In contrast, no such pantothenic acid-releasing compounds were detected in the thermal decomposition test of PTN-SSS in this experimental example. Moreover, unexpectedly, in compositions containing PTN-SSS and pharmaceutically acceptable sugar or silica-based carriers, the generation of thermochromic products (PTN-SS, PTN-SSSS) with structures and generation mechanisms completely different from those of the thermal decomposition products in PTN-SS was significantly suppressed. As a result, the ability to significantly suppress the generation of thermochromic products in PTN-SSS, which has lower stability than PTN-SS, is even more surprising from this perspective.

Claims

1. A pharmaceutical composition comprising a trisulfide compound and a pharmaceutically acceptable carrier, wherein, The trisulfide compound is selected from at least one of the following groups: panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, the compound or a pharmaceutically acceptable salt of formula (1), and glutathione trisulfide or a pharmaceutically acceptable salt thereof. In the formula, X represents -OR 1 or -NR 2 R 3 R 1 R represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. 2 and R 3 Each of the following groups independently represents an alkyl group having 1 to 6 hydrogen atoms or carbon atoms, and the alkyl group may have one or more substituents selected from the group consisting of amino and carboxyl groups. The pharmaceutically acceptable carrier is selected from at least one of the groups consisting of silica-based carriers and sugars.

2. The pharmaceutical composition according to claim 1, wherein, In the formula (1), X is -OH.

3. The pharmaceutical composition according to claim 1, wherein, The trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof.

4. The pharmaceutical composition according to claim 1, wherein, The pharmaceutically acceptable carrier is a silica-based carrier.

5. The pharmaceutical composition according to claim 1, wherein, The trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is a silica-based carrier.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein, The mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition is 2:1 to 1:

50.

7. The pharmaceutical composition according to any one of claims 1 to 5, wherein, The pharmaceutical composition is intended for oral or transdermal administration.

8. The pharmaceutical composition according to claim 1, wherein, The pharmaceutically acceptable carrier is a carbohydrate.

9. The pharmaceutical composition according to claim 1, wherein, The pharmaceutically acceptable carrier is lactose.

10. The pharmaceutical composition according to claim 1, wherein, The trisulfide compound is panthionylamine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is lactose.

11. The pharmaceutical composition according to any one of claims 8 to 10, wherein, The mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition is 1:1 to 1:

20.

12. The pharmaceutical composition according to any one of claims 8 to 10, wherein, The pharmaceutical composition is intended for oral, pulmonary, nasal, intraoral, rectal, or vaginal administration.

13. The pharmaceutical composition according to any one of claims 1 to 5 and 8 to 10, wherein it is a carrier adsorption composition.

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