CN-122003232-A - Pharmaceutical compositions containing trisulfide compounds

Abstract

The invention discloses a pharmaceutical composition which contains a specific trisulfide compound and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is at least one selected from the group consisting of silica gel carriers and saccharides.

Inventors

• Asa Chang Shoichiro
• ISHIMARU HIROAKI
• OHSHIMA ETSUO

Assignees

• 协和医药化工股份有限公司

Dates

Publication Date

20260508

Application Date

20240925

Priority Date

20230928

Claims (13)

1. 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 pantethine trisulfide or a pharmaceutically acceptable salt thereof, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof, and glutathione trisulfide or a pharmaceutically acceptable salt thereof, Wherein X represents-OR 1 OR-NR 2 R 3 ,R 1 represents a hydrogen atom OR an alkyl group having 1 to 6 carbon atoms, R 2 and R 3 each independently represent a hydrogen atom OR an alkyl group having 1 to 6 carbon atoms, the alkyl group may have one OR more substituents selected from the group consisting of an amino group and a carboxyl group, The pharmaceutically acceptable carrier is at least one selected from the group consisting of silica gel type carriers and saccharides.
2. 2. The pharmaceutical composition of claim 1, wherein X in formula (1) is-OH.
3. 3. The pharmaceutical composition of claim 1, wherein the trisulfide compound is pantethine trisulfide or a pharmaceutically acceptable salt thereof.
4. 4. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is a silica gel type carrier.
5. 5. The pharmaceutical composition of claim 1, wherein the trisulfide compound is pantethine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is a silica gel type carrier.
6. 6. The pharmaceutical composition according to any one of claims 1-5, wherein the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition is 2:1-1:50.
7. 7. The pharmaceutical composition according to any one of claims 1 to 5, wherein the pharmaceutical composition is for oral or transdermal administration.
8. 8. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is a saccharide.
9. 9. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is lactose.
10. 10. The pharmaceutical composition of claim 1, wherein the trisulfide compound is pantethine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is lactose.
11. 11. The pharmaceutical composition according to any one of claims 8-10, wherein the mass ratio of the trisulfide compound to the pharmaceutically acceptable carrier in the pharmaceutical composition is 1:1-1:20.
12. 12. The pharmaceutical composition according to any one of claims 8-10, wherein the pharmaceutical composition is for oral administration, pulmonary administration, nasal administration, oral administration, rectal administration or vaginal administration.
13. 13. The pharmaceutical composition according to any one of claims 1 to 5 and 8 to 10, which is a carrier adsorption composition.

Description

Pharmaceutical compositions containing trisulfide compounds Technical Field The present invention relates to pharmaceutical compositions containing trisulfide compounds. Background Compounds containing a covalent structure formed by 3 consecutive sulfur atoms are known as trisulfide compounds. The trisulfide compound has a redox ability according to the valence of the sulfur atom constituting the trisulfide compound, and thus is expected to have various physiologically active functions. For example, non-patent document 1 describes that the administration of polysulfide reduces neurodegeneration in parkinson's disease model mice. Patent document 1 describes pantethine trisulfide as one of trisulfide compounds. Patent document 2 describes a trisulfide compound and its inclusion compound. Patent document 3 describes a method for producing glutathione trisulfide, which is one of trisulfide compounds. Prior art literature Patent literature Patent document 1 International publication No. 2022/045052 Patent document 2 International publication No. 2022/045212 Patent document 3 International publication No. 2021/200487 Non-patent literature Non-patent literature 1：Fumiaki Nagashima et al., "Sulfide：quinone oxidoreductase ameliorates neurodegeneration in a murine model of Parkinson's disease", Redox Biology, 59:102562 (2023). Disclosure of Invention Problems to be solved by the invention In a pharmaceutical composition, the storage stability of the active ingredient in the composition affects the amount of the active ingredient when administered to a subject after the pharmaceutical composition is manufactured, and thus affects the therapeutic effect of the pharmaceutical composition. For example, when the hygroscopicity (deliquescence) of the active ingredient is high, in a pharmaceutical composition whose hygroscopicity is not improved, the active ingredient absorbs moisture and decomposes during storage, and the effective concentration of the active ingredient in the subject to be administered decreases. In addition, in pharmaceutical compositions, the ease of handling represented by fluidity greatly affects the convenience of administration of the composition to patients or the efficiency of packaging the pharmaceutical composition into an amount suitable for administration. Particularly in the case of low flowability of the pharmaceutical composition, it is difficult to ingest, sub-divide or weigh accurate amounts, which in turn may lead to undesired dosing or may cause a loss of a part of the pharmaceutical composition due to adhesion to the device. The object of the present invention is to provide pharmaceutical compositions containing trisulfide compounds. Means for solving the problems The present inventors have found that a pharmaceutical composition containing a trisulfide compound and a specific pharmaceutically acceptable carrier is excellent in storage stability and handling. The present invention relates to the following, for example. [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 pantethine trisulfide or a pharmaceutically acceptable salt thereof, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof, and glutathione trisulfide or a pharmaceutically acceptable salt thereof, (Wherein X represents-OR 1 OR-NR 2R3,R1 represents a hydrogen atom OR an alkyl group having 1 to 6 carbon atoms, R 2 and R 3 each independently represent a hydrogen atom OR an alkyl group having 1 to 6 carbon atoms, and the alkyl group may have one OR more substituents selected from the group consisting of an amino group and a carboxyl group.) The pharmaceutically acceptable carrier is at least one selected from the group consisting of silica gel type carriers and saccharides. [2] The pharmaceutical composition according to [1], wherein X in the above formula (1) is-OH. [3] The pharmaceutical composition according to [1] or [2], wherein the above trisulfide compound is pantethine trisulfide or a pharmaceutically acceptable salt thereof. [4] The pharmaceutical composition according to any one of [1] to [3], wherein the pharmaceutically acceptable carrier is a silica gel carrier. [5] The pharmaceutical composition according to any one of [1] to [4], wherein the trisulfide compound is pantethine trisulfide or a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier is a silica gel type carrier. [6] The pharmaceutical composition according to any one of [1] to [5], wherein the silica gel carrier is a hydrophilic silica gel carrier. [7] The pharmaceutical composition according to any one of [1] to [5], wherein the silica gel carrier is a hydrophobic silica gel carrier. [8] The pharmaceutical composition according to any one of [1] to [7], wherein the mass ratio of the trisulfide compound to the pharmaceutically acceptable carr