Application of rapamycin and structural analogues thereof in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression

A technology similar to rapamycin and its structure is applied in drug combination, drug delivery, antineoplastic drugs, etc. It can solve the problems of no good treatment methods and achieve the effect of alleviating the disease and slowing down the disease phenotype

Active Publication Date: 2020-02-07
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is no good treatment method at home and abroad for the treatment of Paget's disease outside the mammary gland. Once it is diagnosed, it needs to be treated by surgical resection.

Method used

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  • Application of rapamycin and structural analogues thereof in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression
  • Application of rapamycin and structural analogues thereof in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression
  • Application of rapamycin and structural analogues thereof in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Application of Rapamycin in the treatment of Paget disease outside the breast caused by overexpression of Msi1 gene

[0048] (1) Preparation of extramammary mouse Paget disease model (inducible mouse model)

[0049] In this example, a transgenic mouse model (DTG mouse) in which Musashi1 expression was controlled by Doxycyline (Dox) was prepared. By feeding Dox to mice, the overexpression of the foreign gene Musashi1 was induced. After Musashi1 overexpression 48h (ie Dox administration 48h), the initial symptoms of extramammary paget disease can appear.

[0050] The specific preparation method of DTG mice is as follows:

[0051] Mate K14rtta transgenic mice with TRE-Msi1 transgenic mice (see Wang S, Li N, Yousefi M, Nakauka-Ddamba A, Li F, Parada K, et al. (2015) for the construction methods of two transgenic mice. Transformation of the intestinal epithelium by the MSI2 RNA-bindingprotein.Nat Commun 6:6517) to produce offspring mice. When the offspring mice grow to 6...

Embodiment 2

[0171] Example 2 Preparation of Rapamycin cream and its application in the treatment of Paget disease outside the breast caused by overexpression of Msi1 gene

[0172] (1) Preparation method of Rapamycin cream

[0173] 1. The formula of Rapamycin cream:

[0174] Per 100g of distilled water, Rapamycin 0.5g, white petrolatum 6g, ethyl paraben 0.17g, glycerol monostearate 2g, stearic acid 2g, Tween-80 2.8g, stearyl alcohol 13g, glycerol 33g, twelve Sodium alkyl sulfate 0.04g.

[0175] 2. Preparation method:

[0176] Rapamycin cream belongs to O / W type (oil-in-water type).

[0177] (1) Oil phase: each substance (white petrolatum: 6g, ethyl paraben: 0.17g, glyceryl monostearate 2g, stearic acid 2g, Tween-80 2.8g,) is added to the oil pan, and the heating device is turned on Heat and melt, adjust the temperature at 80℃, and keep it warm.

[0178] (2) Water phase: each substance (13g stearyl alcohol, 33g glycerin, add distilled water, heat and melt by heating device, adjust the temperature at ...

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Abstract

The invention discloses an application of rapamycin in preparation of a drug for treating diseases caused by Msi1 gene ectopic overexpression. According to the invention, the inhibitor rapamycin of the m-TOR pathway is used for treating the skin abnormal Paget-like disease caused by Msi1 gene ectopic overexpression for the first time. A rapamycin drug is applied to a mouse model, so that the phenotype of the disease can be well relieved, and the effect of relieving the disease is achieved. Besides, the researched and developed drug is applied to EMPD patients, and a relatively good clinical effect is achieved. The invention provides the new drug for treating the extramammary Paget disease of mice and people.

Description

Technical field [0001] The invention relates to the field of biomedicine, in particular to the application of rapamycin and its structural analogs in the preparation of medicines for treating diseases caused by the ectopic overexpression of Msi1 gene. Background technique [0002] The target protein of rapamycin (Rapamycin) is an atypical serine / threonine protein kinase, which was extracted from the fermentation broth of Streptomyces hygroscopicus in 1975. It was originally used as an antifungal drug. Previous studies have reported that many human genetic diseases, such as tumors, diabetes and other diseases, are related to the abnormal activation of the m-TOR pathway. The molecular weight of m-TOR protein is 289KD, which is essential for the growth and development of mammals (Inoki K , 2005, Nat Genet, 37(1):19-24). Studies have found that m-TOR and Rictor can bind to each other to form a protein complex, which can phosphorylate the amino acids of AKT protein and activate AKT....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/436A61K9/06A61P35/00
CPCA61K31/436A61K9/06A61K9/0041A61K47/26A61K9/0014A61P35/00
Inventor 于政权宋永利
Owner CHINA AGRI UNIV
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