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CN-121971452-A - Application of tripterine or pharmaceutical salt thereof in preparation of medicine for treating ketoacidosis or symptoms caused by ketoacidosis

CN121971452ACN 121971452 ACN121971452 ACN 121971452ACN-121971452-A

Abstract

The invention relates to the technical field of biological medicines, in particular to application of tripterine or medicinal salt thereof in preparation of a medicine for treating ketoacidosis or symptoms caused by ketoacidosis. The invention provides an application of tripterine or a pharmaceutically acceptable salt thereof in preparing a medicament for treating ketoacidosis or symptoms caused by ketoacidosis. The results of the specific embodiment show that the tripterine can obviously reduce the serum beta-hydroxybutyric acid level of mice caused by starvation, the tripterine can obviously reduce the HMGCS2 expression of the livers of the mice, the dapagliflozin obviously promotes the beta-hydroxybutyric acid level, and the tripterine obviously reduces the serum beta-hydroxybutyric acid level of the mice caused by dapagliflozin treatment. Thus, tripterine can be used for treating or improving ketoacidosis or symptoms caused by ketoacidosis. The invention provides a new technical scheme for treating and improving ketoacidosis or symptoms caused by ketoacidosis.

Inventors

  • LIU XIAOJUN
  • Zhu Yinghan
  • YAN LI

Assignees

  • 中国医学科学院基础医学研究所

Dates

Publication Date
20260505
Application Date
20260324

Claims (10)

  1. 1. The application of tripterine or the pharmaceutically acceptable salt thereof in preparing medicaments for treating ketoacidosis or symptoms caused by ketoacidosis.
  2. 2. The use according to claim 1, wherein the ketoacidosis comprises one or more of ketoacidosis, alcoholic ketoacidosis and type 1 diabetic ketoacidosis caused by sodium-glucose cotransporter 2 inhibitors.
  3. 3. The use according to claim 1, wherein the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, nitrate, lactate, hydrobromide, hydroiodide, maleate, fumarate, citrate, formate, benzoate, acetate, trifluoroacetate, mesylate, ethanesulfonate, benzenesulfonate, toluenesulfonate, succinate, salicylate and ascorbate.
  4. 4. The use according to claim 3, wherein the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, lactate, fumarate and citrate.
  5. 5. The use of claim 4, wherein the pharmaceutically acceptable salt comprises a hydrochloride salt.
  6. 6. The use according to claim 1, wherein the medicament further comprises pharmaceutically acceptable excipients.
  7. 7. The application of tripterine or the pharmaceutically acceptable salt thereof in preparing medicaments for preventing ketoacidosis or symptoms caused by ketoacidosis.
  8. 8. The use according to claim 7, wherein the ketoacidosis comprises one or more of ketoacidosis, alcoholic ketoacidosis and type 1 diabetic ketoacidosis caused by sodium-glucose cotransporter 2 inhibitors.
  9. 9. The use according to claim 7, wherein the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, nitrate, lactate, hydrobromide, hydroiodide, maleate, fumarate, citrate, formate, benzoate, acetate, trifluoroacetate, mesylate, ethanesulfonate, benzenesulfonate, toluenesulfonate, succinate, salicylate and ascorbate.
  10. 10. The use according to claim 9, wherein the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, lactate, fumarate and citrate.

Description

Application of tripterine or pharmaceutical salt thereof in preparation of medicine for treating ketoacidosis or symptoms caused by ketoacidosis Technical Field The invention relates to the technical field of biological medicines, in particular to application of tripterine or medicinal salt thereof in preparation of a medicine for treating ketoacidosis or symptoms caused by ketoacidosis. Background Ketogenesis occurs mainly in the mitochondrial matrix of hepatocytes, producing soluble ketone bodies by the breakdown of free fatty acids-acetone (acetone), acetoacetate (AcAc) and β -hydroxybutyrate (β -OHB), which act as energy substrates in extrahepatic tissues. The free fatty acids are activated to acyl-coa under the catalysis of acyl-coa synthetases, then cross the mitochondrial membrane and undergo β -oxidation. The ketogenic rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (3-hydroxy-3-methylglutaryl-CoA synthase 2, hmgcs 2) catalyzes the condensation of acetoacetyl-CoA (acetoacetyl-CoA, acAc-CoA) and acetyl-CoA (acetyl-CoA) to form hydroxymethylglutaryl-CoA. This intermediate is then cleaved by hydroxymethylglutaryl-CoA lyase (hydroxymethylglutaryl-coenzyme A lyase, HMGCL) to release acetyl-CoA and acetoacetate. Acetoacetate may be further reduced to β -hydroxybutyrate or spontaneously decarboxylated to acetone. In the event of depletion of carbohydrate reserves or increased fatty acid supply, ketogenic effects are physiologically enhanced. However, excessive ketone body formation may lead to ketoacidosis, which is characterized by accumulation of acidic ketone bodies. Diabetic ketoacidosis (Diabetic ketoacidosis, DKA) is an acute and life threatening complication of diabetes mellitus characterized by hyperglycemia, metabolic acidosis, and ketosis. Diabetic ketoacidosis (Euglycemic DKA, EDKA) with normoglycemic profile has the same metabolic acidosis and ketosis as DKA, but does not occur with a significant elevation in blood glucose levels (blood glucose <200 mg/dl). EDKA is often not diagnosed or delayed in diagnosis due to its atypical clinical manifestations, thereby delaying treatment. Known EDKA triggers include reduced caloric intake, excessive drinking, chronic liver disease, glycogen storage disease, and recent use of insulin or sodium-glucose cotransporter 2 inhibitors (sodium-glucose cotransporter-2 inhibitors,SGLT2i). SGLT2i is a class of hypoglycemic agents for type 2 diabetes (t 2 d), whose mechanism of action is to inhibit glucose reabsorption by the kidneys. However, SGLT2i increases the risk of diabetic ketoacidosis (including emergency diabetic ketoacidosis). These risks highlight the need for clinically effective prophylactic and therapeutic strategies to address diabetic ketoacidosis caused by SGLT2 i. Disclosure of Invention The invention aims to provide application of tripterine or medicinal salt thereof in preparing medicines for treating ketoacidosis or symptoms caused by ketoacidosis, so as to solve the problems in the prior art. In order to achieve the above object, the present invention provides the following solutions: The invention provides an application of tripterine or a pharmaceutically acceptable salt thereof in preparing a medicament for treating ketoacidosis or symptoms caused by ketoacidosis. Tripterine, also known as celastrol, or Celastrol, or (2R,4aS,6aS,6aR,14aS,14bR)-10-Hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid;(2R,4aS,6aS,12bR,14aS,14bR)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid. In the present invention, the treatment should be given its broadest understanding, including but not limited to improving, alleviating, curing, delaying, preventing recurrence, reducing morbidity. In the present invention, the ketoacidosis or symptoms thereof include exacerbation of diabetes symptoms caused by diseases, gastrointestinal symptoms, respiratory changes, dehydration and shock symptoms and mental changes. Optionally, the ketoacidosis comprises one or more of ketoacidosis, alcoholic ketoacidosis and type 1 diabetic ketoacidosis caused by sodium-glucose cotransporter 2 inhibitors. Optionally, the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, nitrate, lactate, hydrobromide, hydroiodide, maleate, fumarate, citrate (citrate), formate, benzoate, acetate, trifluoroacetate, mesylate, ethanesulfonate, benzenesulfonate, toluenesulfonate, succinate, salicylate and ascorbate. Optionally, the pharmaceutically acceptable salt comprises one or more of hydrochloride, sulfate, phosphate, lactate, fumarate and citrate. Optionally, the pharmaceutically acceptable salt comprises a hydrochloride salt. Optionally, the medicament further comprises pharmaceutically acceptable auxiliary materials. The invention provides an application of tripterine or a pharmaceutically acceptable salt thereof in prepar