CN-121971484-A - Application of tetrathiomolybdate in preparation of medicines for inhibiting inflammatory factor storm

Abstract

The invention provides an application of tetrathiomolybdate in preparing a medicament for inhibiting inflammatory factor storm, belonging to the technical field of medicaments for treating inflammatory factor storm and respiratory diseases. The molecular general formula of the tetrathiomolybdate is X + MoS 4 2‑ Y + , the ionic bond forming positions of 4 sulfide ions of the tetrathiomolybdate are interchangeable, X + and Y + are identical or different cations, and the cations are inorganic cations and/or organic cations which can be dissociated in a solution to generate MoS 4 2‑ or can be enzymatically hydrolyzed in a biological system to generate MoS 4 2‑ . The invention discloses the unique advantages of a single-drug scheme in diseases related to inflammatory factor storm and respiratory system, especially bacterial acute respiratory system inflammation for the first time, and tetrathiomolybdate is used as a single active ingredient for preparing the medicine for treating bacterial pneumonia and non-viral acute lung injury/acute respiratory distress syndrome.

Inventors

• YAN XIQUAN
• HAN XIAOTONG
• LU SIYU
• ZHOU XIANGYI
• ZENG YUTENG
• DAI PEI
• CHEN BAILIN
• LI JUN
• CAO YAN
• Fan Maiying

Assignees

• 湖南省人民医院(湖南师范大学附属第一医院)

Dates

Publication Date

20260505

Application Date

20260305

Claims (10)

1. 1. An application of tetrathiomolybdate in preparing medicines for inhibiting inflammatory factor storm is provided.
2. 2. The use according to claim 1, wherein the inflammatory factor storm is associated with a respiratory disease.
3. 3. The use according to claim 2, wherein the respiratory disease is bacterial acute respiratory inflammation.
4. 4. The use according to claim 1, wherein the tetrathiomolybdate has the general molecular formula X + MoS 4 2- Y + , which has the structural formula: ; The positions of the ionic bonds of 4 sulfide ions of the tetrathiomolybdate can be exchanged, X + and Y + are identical or different cations, and the cations are inorganic cations and/or organic cations which can be dissociated in a solution to generate MoS 4 2- or can be enzymatically hydrolyzed in a biological system to generate MoS 4 2- .
5. 5. The use according to claim 1, wherein the inorganic cations comprise at least one of Na + 、K + or NH 4 + and the organic cations comprise at least one of amine ions or choline ions.
6. 6. The use of claim 1, wherein the tetrathiomolybdate comprises at least one of (NH 4 ) 2 MoS 4 、Na 2 MoS 4 or K 2 MoS 4 .
7. 7. The use according to claim 1, wherein the administration of the medicament comprises oral, inhalation, intravenous injection, intramuscular injection or airway instillation.
8. 8. The use according to claim 1, wherein the pharmaceutical dosage form comprises an oral formulation, an inhaled formulation, an intravenous formulation, an intramuscular formulation or an airway instillation formulation.
9. 9. The use according to claim 8, wherein the oral formulation comprises a capsule, a granule, a tablet, and the inhalant formulation comprises a spray, an aerosol, a dry powder inhalant, or a combination thereof.
10. 10. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier comprising at least one of a propellant, a dispersant, a surfactant, a liquid carrier, and/or a solid carrier.

Description

Application of tetrathiomolybdate in preparation of medicines for inhibiting inflammatory factor storm Technical Field The invention relates to the technical field of medicines for treating inflammatory factor storm and bacterial acute respiratory inflammatory diseases, in particular to application of tetrathiomolybdate in preparation of medicines for inhibiting inflammatory factor storm. Background Acute respiratory inflammatory diseases (e.g., bacterial pneumonia, non-viral acute lung injury/acute respiratory distress syndrome) are clinically common critical conditions, and their core pathological mechanisms involve excessive activation of the immune system, manifested by cascade release of pro-inflammatory cytokines (e.g., TNF- α, IL-1β, IL-6), massive neutrophil infiltration, and oxidative damage to lung tissue. The disease progresses rapidly, which is easy to cause the destruction of alveolar-capillary barrier, pulmonary edema and multiple organ dysfunction, and has high mortality. Current standard treatment regimens rely primarily on broad spectrum antibiotics in combination with glucocorticoids, aimed at controlling infections and inhibiting inflammatory responses. However, the glucocorticoid is easy to cause serious side effects such as immunosuppression, blood glucose metabolic disorder, osteoporosis and the like after long-term use, has limited curative effects on partial severe patients (such as drug-resistant bacteria infection or immunodeficiency patients), and highlights the defects of the existing treatment. Tetrathiomolybdate (Tetrathiomolybdate, TTM) as a sulfur-containing metal complex has been studied in the past with a focus on its copper chelating ability for use in wilson's disease treatment and its protective effect on antioxidant properties in liver fibrosis models. These studies demonstrate that TTM can exert therapeutic potential by modulating metal ion homeostasis and oxidative stress pathways, but its mechanism of action in respiratory disease is not yet defined. Notably, TTM is commonly used in the art for non-inflammatory diseases or in combination with other drugs, e.g., patent CN 116546987A "methods and compositions for treating coronaviruses, influenza and acute respiratory distress syndrome" discloses a combination regimen of TTM with a 5-lipoxygenase inhibitor (e.g., ethanamine) for viral respiratory diseases. However, this regimen is directed against viral pathogens and the combination may increase the risk of drug interactions, and does not involve the applicability of TTM as a single drug for the treatment of bacterial acute respiratory inflammation. At present, although the combined administration scheme can partially relieve inflammation, the problems of large individual difference, superimposed side effects and the like exist. Especially for bacterial inflammation, single-drug treatment has the potential advantages of simplifying the drug administration process, improving the safety and reducing the clinical management cost. However, the role of TTM single agents in modulating lung tissue-specific inflammatory pathways (e.g., inhibiting NF- κb signaling and reducing neutrophil migration) has not been revealed, and their anti-inflammatory effects and mechanisms in bacterial models of pneumonia remain in the open field. Therefore, the feasibility and uniqueness of the TTM as a single drug for treating bacterial acute respiratory inflammation are clear, the blank of the prior art can be filled, and an important direction is provided for developing novel anti-inflammatory drugs. Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides an application of tetrathiomolybdate in preparing medicines for inhibiting inflammatory factor storm. Compared with the prior art, the invention discloses the unique advantages of a single-drug scheme in bacterial acute respiratory inflammation for the first time, and tetrathiomolybdate is used as a single active ingredient for preparing the drug for treating bacterial pneumonia and non-viral acute lung injury/acute respiratory distress syndrome. The technical scheme of the invention is as follows: Use of tetrathiomolybdate in the manufacture of a medicament for inhibiting an inflammatory factor storm, further wherein the inflammatory factor storm is associated with a respiratory disease. Further, the respiratory disease is bacterial acute respiratory inflammation. The molecular general formula of the tetrathiomolybdate is X +MoS42-Y+, and the structural formula is as follows: ; The positions of the ionic bonds of 4 sulfide ions of the tetrathiomolybdate can be exchanged, X + and Y + are identical or different cations, and the cations are inorganic cations and/or organic cations which can be dissociated in a solution to generate MoS 42- or can be enzymatically hydrolyzed in a biological system to generate MoS 42-. Experiments of the inventor show that the active unit of the tetrathiomolybdate is mainl