CN110664814A - Application of FG-4592 in preparation of medicines for treating inflammatory bowel diseases - Google Patents

Abstract

The invention relates to the field of biomedicine, in particular to the use of FG-4592 in the preparation of a medicine for treating inflammatory bowel disease.

Description

Use of FG-4592 in the preparation of medicaments for the treatment of inflammatory bowel disease

technical field

The invention relates to the field of biomedicine, in particular to the use of FG-4592 in the preparation of a medicine for treating inflammatory bowel disease.

Background technique

Inflammatory bowel disease (IBD) is a chronic relapsing disease characterized by nonspecific inflammatory damage to the intestine, including ulcerative colitis (UC) and Crohn's disease. Through colonoscopy, intestinal mucosal congestion, edema, granular changes and even ulceration can be observed; histopathologically, extensive ulceration in the lesion area is accompanied by a large number of neutrophil infiltration and intestinal mucosal necrosis. However, the pathogenesis of inflammatory bowel disease has not yet been definitively concluded, and it may be related to genetic susceptibility, external environmental stimuli, autoimmunity, and intestinal flora imbalance.

FG-4592 is a HIFα prolyl hydroxylase inhibitor and stabilizes HIF-2 while inducing EPO production, which has a significant protective effect against TBHP-induced cell death, in addition, in a mouse model of spinal cord injury, Administration of FG-4592 promotes injury repair while increasing neuronal survival at the site of spinal cord lesions. In 2014, the drug was declared for clinical trials in China as a class 1.1 new drug. The Chinese name is Kebomei Capsules. Phase III clinical studies have been carried out in my country.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a new application of FG-4592.

In the first aspect of the present invention, there is provided the use of FG-4592 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of inflammatory bowel disease.

As the pharmaceutically acceptable salts, for example, metal salts, halide salts, salts with organic bases, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids and the like can be mentioned. Non-limiting examples of metal salts include, but are not limited to, alkali metal salts, such as sodium, potassium, and the like; alkaline earth metal salts, such as calcium, magnesium, barium, aluminum, and the like. Non-limiting examples of salts formed with inorganic acids include, but are not limited to, salts formed with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. Non-limiting examples of salts with organic acids include, but are not limited to, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, malic acid, maleic acid, tartaric acid, citric acid, succinic acid, methanesulfonic acid, benzene Salts formed from sulfonic acid, p-toluenesulfonic acid, etc.

FG-4592, as a HIFα prolyl hydroxylase inhibitor, was unexpectedly discovered by the inventors during the screening process, and it has a new use in the treatment of inflammatory bowel disease.

The second aspect of the present invention provides a pharmaceutical composition, which is characterized in that it contains a therapeutic amount of FG-4592 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

The beneficial effect of the present invention lies in finding and confirming for the first time that FG-4592 has a good therapeutic effect on DSS-induced enteritis in mice.

Description of drawings

Fig. 1 is a line chart of the survival period of mice in the control group (n=11) and the treatment group (n=12) after oral administration of DSS drinking water;

Figure 2 is a scatter diagram showing the comparison of the number of erythrocytes in the peripheral blood of mice in the control group (n=6) and the treatment group (n=6) after oral administration of DSS drinking water for 7 days;

Figure 3 is a scatter diagram showing the comparison of hematocrit in peripheral blood of mice in the control group (n=6) and the treatment group (n=6) after 7 days of oral administration of DSS drinking water;

Figure 4 is a comparison of typical colon photographs of mice in the control group (n=6) and the treatment group (n=6) after 7 days of oral administration of DSS drinking water.

Detailed ways

The following examples illustrate the present invention, but do not limit the present invention. In the art, simple replacements or improvements made by a skilled person to the present invention all belong to the technical solutions protected by the present invention.

Materials and Methods:

Mice: Male wild-type C57 mice (6-8 weeks) were purchased from the Chinese Academy of Sciences (Shanghai). All mice were housed in the Special Pathogen Free (SPF) laboratory of the Second Military Medical University (Shanghai) Animal Experiment Center. Mice in the treatment group were given intraperitoneal injection of 25 mg/kg FG-4592 (Medchemexpress, MCE, USA) for 3 consecutive days, and then given 1.5% DSS (40,000 kDa; ICNBiochemicals) drinking water orally for 7 days and then returned to normal drinking water. The mice in the control group and the mice in the treatment group were given 1.5% DSS drinking water orally for 7 days and then changed to normal drinking water.

Survival period experiment: The survival period of mice in the control group (n=11) and the treatment group (n=12) was recorded after oral administration of DSS drinking water.

Analysis of peripheral blood: the mice in the control group (n=6) and the treatment group (n=6) drank 1.5% DSS water. On the 7th day, the mice were under anesthesia. A centrifuge tube (EP tube) with K2-EDTA was placed. Red blood cells and hematocrit were determined by a standard hematology analyzer in the laboratory of the Animal Experiment Center, Second Military Medical University.

Intestinal damage analysis: mice in the control group (n=6) and treatment group (n=6) drank 1.5% DSS water on the 7th day, the mice were killed by cervical dislocation, and the colons of the two groups of mice were collected for comparative analysis.

Results: The survival period of FG-4592 mice was better than that of control mice (Figure 1). Specifically, FG-3592 mice were observed for 15 days, one died at 10 days, 2 died at 12 days, and a total of 3 mice died , the other all alive, the average survival days of the control group was 9.09 days. The anemia symptoms of the control mice were more severe than those of the FG-4592 mice, and the peripheral blood RBC and HCT of the FG-4592 mice were higher than those of the control mice (Figures 2 and 3). The intestinal damage of the control mice was more severe than that of the FG-4592 mice, with shortened intestines and obvious bloody stools (Figure 4). In conclusion, FG-4592 has obvious protective effect on DSS-induced intestinal inflammatory injury in mice.

The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, some modifications and improvements can be made without departing from the inventive concept of the present invention, which belong to the present invention. The scope of protection of the invention.

Claims (2)

1. Use of FG-4592 or a pharmaceutically acceptable salt thereof in the treatment of inflammatory bowel disease. 2. A pharmaceutical composition, characterized in that it contains a therapeutic amount of FG-4592 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable adjuvant.

Images