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Application of STAT3 agonist Colivelin TFA in treatment of HIES and osteoporosis

An osteoporosis and agonist technology, applied in the field of medical applications, can solve problems such as the unexplained role of the skeletal system, and achieve the effects of increasing bone mass, promoting bone metabolism, and avoiding osteonecrosis of the jaw

Pending Publication Date: 2021-07-30
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

Previous studies have demonstrated that Colivelin TFA can be used in Alzheimer's disease and ischemic brain injury, but its role in the skeletal system has not been elucidated

Method used

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  • Application of STAT3 agonist Colivelin TFA in treatment of HIES and osteoporosis
  • Application of STAT3 agonist Colivelin TFA in treatment of HIES and osteoporosis
  • Application of STAT3 agonist Colivelin TFA in treatment of HIES and osteoporosis

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Experimental program
Comparison scheme
Effect test

Embodiment

[0022] Experimental materials: Colivelin TFA was purchased from MCE Company.

[0023] Experimental steps:

[0024] a) Obtain Stat3 by homologous recombination flox / flox mice. Using Tool Mouse Osx cre with Stat3 flox / flox Specific knockout of Stat3 (Osx Cre ;Stat3 fl / fl ) of C57BL6 mice, the process is as follows figure 1 Shown in A.

[0025] b) Take Day 1Osx Cre and Osx Cre ;Stat3 fl / fl Mouse calvarial bone cells, western detection of STAT3 protein expression level in the calvarial bone, to verify whether the bone precursor cell-specific knockout of Stat3 mice was successfully constructed, the specific results are as follows figure 1 As shown in B, the results show that osteoblast-specific knockout mice for Stat3 were successfully constructed. 8 weeks old Osx cre and Osx cre ;Stat3 fl / fl Overall view of mice figure 1 Shown in C.

[0026] c) Take Day 1Osx Cre and Osx Cre ;Stat3 fl / fl Stain the mice as a whole to study whether there are differences in the bone...

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Abstract

The invention relates to an application of an STAT3 agonist ColivelinTFA in treatment of HIES and osteoporosis. An osteoblast specific Stat3 knockout mouse is constructed through a Cre-loxp system, it is found that the mouse shows HIES-related bone deformity such as maxillofacial bone development deformity, spontaneous fracture and osteoporosis, and the mechanism that STAT3 inactivation causes HIES-related bone development deformity and osteoporosis by regulating osteogenic activity is proved. On the basis, it is proved that the STAT3 agonist ColivelinTFA can be used for treating osteoporosis caused by insufficient single dosage of STAT3 and stress loss. Compared with a diphosphate drug, the ColivelinTFA increases the bone mass by promoting bone metabolism instead of inhibiting bone metabolism, which may avoid a series of complications such as jaw bone necrosis caused by diphosphate to a certain extent.

Description

technical field [0001] The invention relates to the technical field of medical applications, in particular to the application of STAT3 agonist Colivelin TFA in the treatment of HIES and osteoporosis. Background technique [0002] Mutation and inactivation of human STAT3 gene will form a complex primary immunodeficiency disease characterized by elevated serum IgE concentration, known as hyper IgE syndrome (HIES). Spontaneous fracture is a common clinical manifestation of HIES. A cohort study showed that 57% of patients had at least 3 fractures, which could occur in all age groups; further analysis found that the bone mineral density of femur and vertebrae in patients with spontaneous fractures lower than normal. The clinical drug treatment for osteoporosis is divided into two categories, one is antiresorptive drugs, which can slow down the resorption of bone by osteoclasts; the other is anabolic drugs, which can stimulate osteoblasts to form new bone. Bisphosphonates as ant...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61K38/08A61P19/10
CPCA61K38/16A61K38/08A61P19/10
Inventor 江凌勇周巳入代庆刚黄湘如
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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