CN109925316B

CN109925316B - Medicine for treating ulcerative colitis

Info

Publication number: CN109925316B
Application number: CN201910235424.9A
Authority: CN
Inventors: 晏杰; 陶爱林; 张冲; 何巧玲; 罗以琴; 刘帅; 何安东
Original assignee: Second Affiliated Hospital of Guangzhou Medical University
Current assignee: Second Affiliated Hospital of Guangzhou Medical University
Priority date: 2019-03-26
Filing date: 2019-03-26
Publication date: 2021-09-14
Anticipated expiration: 2039-03-26
Also published as: CN109925316A

Abstract

The invention discloses a medicine for treating ulcerative colitis, which has the following structural formula:

Description

Medicine for treating ulcerative colitis

Technical Field

The invention relates to a medicament for treating colitis, in particular to a medicament for treating ulcerative colitis.

Background

The therapeutic means of ulcerative colitis mainly include drug therapy and surgical therapy. The drug treatment comprises: (1) sulfasalazine and salicylic acid preparations are main medicines for treating ulcerative colitis, but the long-term treatment effect is poor; (2) corticosteroids, such as dexamethasone or prednisone, however long-term hormone maintenance does not prevent recurrence of ulcerative colitis; and whether the hormone can be continuously used in the chronic period is different, and has certain side effects (the steroid medicine can increase the risk of infection); (3) immunosuppressive agents, however, have questionable efficacy and may also increase the risk of infection and cancer. In conclusion, none of the current drugs for treating ulcerative colitis can achieve the effect of long-term prevention or treatment; on the other hand, after the ulcerative colitis patient is treated by the total resection of the rectum, the patient still needs to pay special attention to the care in life, and the patient must pay special attention to the combination of labor and ease, so that the patient cannot be tired too much, and particularly some patients with serious illness should be bedridden for rest in time.

Disclosure of Invention

Based on the problems, the invention aims to overcome the defects of the prior art and provide a medicament with remarkable effect on treating ulcerative colitis.

In order to achieve the purpose, the invention adopts the technical scheme that: a medicament for the treatment of ulcerative colitis, wherein the formula of said medicament (LY3009120) is as follows:

as a further optimization of the above protocol, the drug (LY3009120) was used in a dose of 20mg/KG body weight. According to needs, the medicine for treating ulcerative colitis can be prepared into tablets, pills, powder granules and the like by adding corresponding auxiliary materials on the basis of LY 3009120.

As a further optimization of the above protocol, the drug (LY3009120) was administered by intraperitoneal injection.

In conclusion, the beneficial effects of the invention are as follows:

the medicament (LY3009120) has obvious curative effects on treating ulcerative colitis, including remarkably inhibiting the weight loss of mice, remarkably improving the survival rate of the mice, remarkably inhibiting the shortening of the colon of the mice induced by DSS and remarkably inhibiting the damage of the colon epithelial cell barrier of the mice induced by DSS.

Drawings

FIG. 1 is a graph showing the results of the weight change of the mice of each group in example 1;

FIG. 2 is a graph showing the survival rate of each group of mice in example 1;

FIG. 3 is a graph showing the results of colon length in each group of mice in example 2;

FIG. 4 is a graph showing the results of the degree of disruption of the colonic epithelial cell barrier in each group of mice in example 3.

Detailed Description

The invention finds a compound LY3009120 with obvious curative effect on ulcerative colitis from the pathogenesis of the ulcerative colitis, wherein the structural formula of the LY3009120 is as follows:

this compound (LY3009120) is an anticancer drug and has been used in first-phase clinical trials. The inventor of the application finds that the application dose of LY3009120 is 20mg/Kg mouse, and the mouse has obvious curative effect on ulcerative colitis when being injected by an abdominal cavity, and the application dose is specifically embodied in the following aspects: the mouse colon epithelial cell barrier inhibitor can obviously inhibit the weight loss of mice, obviously improve the survival rate of the mice, obviously inhibit the shortening of the mouse colon induced by DSS and obviously inhibit the damage of the mouse colon epithelial cell barrier induced by DSS.

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments. Unless otherwise specified, the experimental methods in the present invention are all conventional methods; unless otherwise specified, the concentrations of the reagents in the present invention are mass concentrations; the materials or agents of the present invention are commercially available or may be obtained from other publicly available sources, unless otherwise specified.

Example 1 study of LY3009120 on the changes in body weight and survival rates of DSS-induced ulcerative colitis mice

The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 2 groups (8 mice per group): vehicle group (PBS containing 10% DMSO and 20% cyclodextin) and LY3009120 group (20mg/Kg mic dissolved in PBS containing 10% DMSO and 20% cyclodextin). 3% DSS (dextran sulfate sodium) was fed daily and Vehicle or LY3009120(20mg/Kg mice) was intraperitoneally injected daily, seven days later, the DSS was withdrawn and the intraperitoneal injection of Vehicle or LY3009120 was continued, 3 days later, no more injections were given. Mice were weighed daily and counted for mortality, and the results are shown in figures 1 and 2.

The experimental results are as follows: figure 1 shows that LY3009120 significantly inhibited the reduction of body weight in mice, P <0.05, > P <0.01, > P < 0.001; fig. 2 shows that LY3009120 can significantly improve the survival rate of mice.

Example 2 Effect of LY3009120 on Colon Length in DSS-induced ulcerative colitis mice

The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 3 groups: control group 4, DMSO group 4, LY3009120 group 4. The control group was fed water daily; the group of Vehicle and LY3009120 was fed 3% DSS daily and Vehicle or LY3009120(20mg/Kg mice) was intraperitoneally injected daily, seven days later, the DSS was removed and the length of the colon of the mice was measured. The experimental result is shown in figure 3, and the result shows that LY3009120 can obviously inhibit DSS-induced colon shortening of mice.

Example 3 Effect of LY3009120 on DSS-induced disruption of the intestinal epithelial cell barrier in ulcerative colitis

The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 3 groups: control group 4, DMSO group 4, LY3009120 group 4. The control group was fed water daily; groups of Vehicle and LY3009120 were fed 3% DSS daily and Vehicle or LY3009120(10mg/Kg mice) were intraperitoneally injected daily, seven days later, the DSS was removed, colon tissue was removed, fixed with 4% paraformaldehyde, and HE stained. The experimental results are shown in fig. 4, and fig. 4 shows that LY3009120 can significantly inhibit DSS-induced disruption of the mouse colonic epithelial cell barrier.

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. Use of a drug LY3009120 in the manufacture of a medicament for the treatment of ulcerative colitis, wherein the drug LY3009120 has the formula shown below:

2. the use according to claim 1, wherein the medicament LY3009120 is used in a dose of 20mg/KG body weight.

3. The use according to claim 1 or 2, wherein the drug LY3009120 is administered by intraperitoneal injection.