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Applications of lesinurad or pharmaceutically acceptable salt thereof in preparation of drugs for treatment or prevention of Cushing's syndrome

A technology for Cushing's syndrome and medicine is applied in the application field of lesinurad or a pharmaceutically acceptable salt thereof in the preparation of medicines for treating or preventing Cushing's syndrome, so as to improve the quality of life, reduce various indicators, and improve the disease condition. Effect

Inactive Publication Date: 2018-05-11
JIANGSU WANBANG BIOPHARMLS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It can be seen that the existing patents do not disclose that lesinurad can treat Cushing's syndrome

Method used

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  • Applications of lesinurad or pharmaceutically acceptable salt thereof in preparation of drugs for treatment or prevention of Cushing's syndrome
  • Applications of lesinurad or pharmaceutically acceptable salt thereof in preparation of drugs for treatment or prevention of Cushing's syndrome
  • Applications of lesinurad or pharmaceutically acceptable salt thereof in preparation of drugs for treatment or prevention of Cushing's syndrome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The therapeutic effect of lesinurad on Cushing's syndrome

[0027] 1. Materials and methods

[0028] 1.1 Experimental objects and grouping

[0029] 22 patients with Cushing's syndrome were randomly hospitalized (Cushing group), including 5 males and 17 females, with an average age of (40.25±10.24) years and a medical history of 6 months to 10 years. Among them, there were 14 cases of Cushing's disease, 6 cases of adrenal sebaceous adenoma, 1 case of ACTH-independent macronodular hyperplasia, and 1 case of ectopic ACTH syndrome. The diagnosis was made based on the patient's clinical manifestations, cortisol, blood ACTH, dexamethasone suppression test, adrenal CT, pituitary MRI and other examinations, and some patients were confirmed by pathological examination after surgery. In the past 3 months, he has not taken drugs that affect blood sugar, blood lipids, and blood uric acid metabolism. There was no statistically significant difference between the two groups in term...

Embodiment 2

[0040] Therapeutic effect of lesinurad combined with drugs that specifically act on pituitary adenomas to inhibit ACTH secretion and rosiglitazone on Cushing's syndrome

[0041] In vitro experiments have confirmed that high concentrations of PPARγ receptor agonists such as rosiglitazone [150mg / (kg·d)] can inhibit the proliferation of mouse AtT20 tumor cells cultured in vitro, and 69% of the tumor-planted mice did not Cushing's syndrome appeared, which also reduced ACTH levels by 65% ​​and cortisol levels by 91%.

[0042] In vitro experiments have confirmed that high concentrations of PPARγ receptor agonists such as rosiglitazone [150mg / (kg·d)] combined with lesinurad [800mg / (kg·d)] can inhibit the proliferation of mouse AtT20 tumor cells cultured in vitro, In mice implanted with tumors, 81 percent were free of Cushing's syndrome, while ACTH levels were reduced by 77 percent and cortisol levels were reduced by 97 percent.

Embodiment 3

[0044] Combination of lesinurad with cortisol synthesis-inhibiting drugs acting on adrenal tumors and trolosteine ​​in the treatment of Cushing's syndrome

[0045] Trilosteine ​​is a competitive inhibitor of the cholesterol synthase 3-beta hydroxysteroid dehydrogenase, which blocks the conversion of pregnenolone to progesterone, ultimately reducing the synthesis of cortisol, aldosterone, and androstenedione. In 7 patients with Cushing's disease, the application of trilosteine ​​can reduce the level of steroids, serum cortisol and 17-hydroxysteroids can be reduced by 50%, and urinary free cortisol can be reduced by 70%. Another 7 patients with Cushing's disease were treated with the combination of trilosteine ​​and lesinurad, and found that serum cortisol and 17 hydroxysteroids could be reduced by 59%, and urinary free cortisol could be reduced by 79%.

[0046] 3 Conclusion

[0047] The pathological basis of metabolic syndrome is central obesity and metabolic disorders, and in...

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Abstract

The present invention relates to new uses of a drug, particularly to applications of lesinurad or a pharmaceutically acceptable salt thereof in preparation of drugs for treatment or prevention of Cushing's syndrome. According to the present invention, the research results show that patients with Cushing's syndrome have insulin resistance, and uric acid is closely related with obesity, hypertension, glucose-lipid metabolism disorder and metabolic syndrome; the research results show that the incidence of metabolic syndrome can be increased along with the increase of the blood uric acid level soas to promote the occurrence of other components of metabolic syndrome; and lesinurad is a uric acid excretion promoting agent, and can inhibit URAT1 and OAT4 so as to reduce the blood uric acid level, such that the treatment effect or the assisted treatment effect is further provided for Cushing's syndrome.

Description

technical field [0001] The present invention relates to a new application of lesinurad, in particular to the application of lesinurad or a pharmaceutically acceptable salt thereof in the preparation of medicaments for treating or preventing Cushing's syndrome. Background technique [0002] Cushing's syndrome (CS) is a syndrome characterized by central obesity, hypertension, hypokalemia, and osteoporosis caused by an increase in endogenous cortisol. The cause may be excessive secretion of adrenocorticotropic hormone (ACTH) by pituitary tumors or ectopic neuroendocrine tumors to stimulate adrenal glands to secrete cortisol, or it may be caused by excessive secretion of cortisol by adrenal tumors or hyperplasia. The former becomes ACTH-dependent Cushing syndrome, the latter became ACTH-independent Cushing's syndrome. The preferred treatment is surgery, but in clinical practice, it is difficult to locate and diagnose ACTH-dependent Cushing's syndrome, and some patients cannot b...

Claims

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Application Information

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IPC IPC(8): A61K31/4196A61K31/4439A61K31/58A61K45/06A61P5/38A61P3/04A61P9/12A61P19/10A61P7/00A61P3/12
CPCA61K31/4196A61K31/4439A61K31/58A61K45/06A61K2300/00
Inventor 李惠珠王伟乔德水
Owner JIANGSU WANBANG BIOPHARMLS
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