Application of sorafenib to preparing medicine for preventing, alleviating and/or treating fatty liver and related diseases

A technology for fatty liver and steatohepatitis, which can be used in drug combinations, antineoplastic drugs, active ingredients of heterocyclic compounds, etc., can solve the problems such as the unreported treatment effect of NAFLD, save time and financial resources, have obvious curative effect, and reduce lipids. The effect of deposition inhibition

Inactive Publication Date: 2018-05-01
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But there is no report about the therapeutic effect

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  • Application of sorafenib to preparing medicine for preventing, alleviating and/or treating fatty liver and related diseases
  • Application of sorafenib to preparing medicine for preventing, alleviating and/or treating fatty liver and related diseases
  • Application of sorafenib to preparing medicine for preventing, alleviating and/or treating fatty liver and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] [Example 1] Effect of Sorafenib Pretreatment on Fat Accumulation in L02 Cells

[0065] The L02 cells were divided into 4 groups, namely DMSO BSA group, DMSO PA / OA group, sorafenib 2 μM PA / OA group and sorafenib 6 μM PA / OA group. After the cells adhered to the wall, they were treated with DMSO, 2 μM sorafenib and 6 μM sorafenib for 3 h, and then treated with 0.2 / 0.4 mM PA / OA for 12 h. BSA treatment was used as a control for oil red O staining. The staining result is as figure 1 : Compared with the control group (DMSO group), the red fat droplets in the cells of the inhibitor pretreatment group were significantly reduced. The results indicated that Sorafenib significantly inhibited lipid accumulation in L02 cells, and significant changes could be seen when the pretreatment concentration of Sorafenib was 2 μmol.

Embodiment 2

[0066] [Example 2] Effect of Sorafenib Pretreatment on Fat Accumulation in Primary Hepatocytes of Mouse

[0067] The mouse primary hepatocytes were divided into 4 groups, namely DMSO BSA group, DMSO PA / OA group, sorafenib 2 μM PA / OA group and sorafenib 6 μM PA / OA group. After the cells adhered to the wall, they were treated with DMSO, 2 μM sorafenib, and 6 μM sorafenib for 3 h, and then treated with 0.2 / 0.4 mM PA / OA for 12 h. BSA treatment was used as a control for oil red O staining. The staining result is as figure 2 : Compared with the DMSO group, the amount of red fat droplets in the inhibitor pretreatment group was significantly reduced. The results indicated that fat accumulation in L02 cells was significantly inhibited after pretreatment with sorafenib inhibitor. When the sofepramine was 6 μmol, the significant inhibitory effect of sofepramine on lipid accumulation could be detected in primary mouse hepatocytes.

Embodiment 3

[0068] [Example 3] Effect of Sorafenib on lipid accumulation in mouse liver

[0069] C57 male mice (20 in total) were fed with high-fat and high-cholesterol (HFHC) for 15 weeks (to establish NASH model) and were divided into two groups (10 in each group, respectively, the administration group and the control group). / kg) and vehicle (DMSO: Solutol: PEG400: water = 5:10:20:65 (v:v:v:v)) (dosing frequency: once every other day), while continuing to feed HFHC for 4 weeks, then take samples. The liver weights of the two groups of mice were measured, and oil red O staining, H&E staining and PSR staining were performed on the livers of the mice.

[0070] The results of the changes in the body weight and liver weight of the two groups of mice were as follows: image 3 As shown, the body weight and liver weight of mice administered with soferanib were significantly lower than those of mice in the control group. pass Figure 4-6 The oil red O staining, H&E staining, and PSR staining...

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Abstract

The invention discloses application of sorafenib to preparing a medicine for preventing, alleviating and/or treating fatty liver and related diseases, and belongs to novel application of the medicineof the sorafenib. The medicine taking the sorafenib as the active ingredient and used for preventing, alleviating and/or treating fatty liver and related diseases has the following advantages: 1, thesorafenib belongs to a medicine approved by U.S.FDA, and therefore, the existing huge toxicity and dosage data of the medicine are utilized, and a large amount of time and a large number of financialresources are saved; and 2, the curative effect is obvious, the sorafenib obviously inhibits the accumulation of lipid in a cell L02, and the obvious change is seen when the pretreatment concentrationof the sorafenib is 2 [mu]mol; when the pretreatment concentration of the sorafenib is 6 [mu]mol, the sorafenib is detected to obviously inhibit the accumulation of the lipid in the primary hepatocyte of a mouse; and in addition, the sorafenib has an obvious effect of inhibiting the accumulation of the lipid caused by the induction of the HFHC (High Fat and High Cholesterol) diet. The sorafenib has a broad application prospect in the medical field.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of a known clinical medicine sorafenib in the preparation of medicines for preventing, alleviating and / or treating fatty liver and related diseases. Background technique [0002] With the development of social economy and the change of residents' diet, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease affecting the world, and the main cause of the disease is obesity. In developed countries, the obesity rate of adults and children is increasing year by year[1,2], and NAFLD has become the most common chronic liver disease in Western countries. In developing countries, the incidence of NAFLD is also increasing year by year, and in local areas, the incidence rate soars to 65% [3,4]. Due to differences in fat and muscle composition, Asians are genetically susceptible [5]. Today, NAFLD is the second most common liver disease in my coun...

Claims

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Application Information

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IPC IPC(8): A61K31/44A61P1/16A61P35/00
Inventor 李红良
Owner WUHAN UNIV
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