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Application of interleukin (IL-22) antibody in preparing medicines for treating adenomyosis

Adenomyosis and antibody technology, applied in the field of medicine, can solve problems such as proliferation, invasion, and low pain relief rate

Inactive Publication Date: 2017-08-11
THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies at home and abroad believe that the etiology may be related to the lack of submucosa in the uterus. The lack of submucosa in the uterus may cause endometrial basal layer cells to proliferate and invade into the myometrium, accompanied by compensatory enlargement of surrounding myometrial cells to form a lesions, however, to date, there are still too many unsolved mysteries about the pathogenesis of AD
Medicine and surgical treatment are still the main treatment measures at present, but the pain relief rate after simple lesion resection is low and the recurrence rate is high

Method used

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  • Application of interleukin (IL-22) antibody in preparing medicines for treating adenomyosis
  • Application of interleukin (IL-22) antibody in preparing medicines for treating adenomyosis
  • Application of interleukin (IL-22) antibody in preparing medicines for treating adenomyosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1 in vitro experiment

[0040] 1) IL-22 receptor is expressed in AD ectopic lesions

[0041] First, through immunohistochemical staining (the immunohistochemical kit was purchased from Beijing Zhongshan Jinqiao Co., Ltd.), it was found that the intima of AD lesions highly expressed and the vascular endothelium expressed moderately IL-22 receptors, IL-22R1 and IL-10R2 (IL-22 receptors). The body was purchased from R&D company) (such as figure 1 shown);

[0042] 2) IL-22 antibody significantly inhibited the promoting effect of ESC on the viability and activation of HUVECs

[0043] The intimal tissues of AD patients were collected, digested with IV collagenase (Sigma) and isolated and cultured as primary ESCs. An indirect co-culture (transwell chamber, Corning) of ESCs and HUVECs was established, with or without IL-22 neutralizing antibody (R&D Company) added to the co-culture system, and cultured for 48 hours. CCK8 (Dong Ren Chemical Company) experiments s...

Embodiment 2

[0049] Embodiment 2 constructs AD mouse model

[0050] Healthy newborn female ICR mice (Shanghai Slack Experimental Animal Co., Ltd.), 2-5 days after birth, orally administered tamoxifen (tamoxifen 2.7umol / kg, dissolved in peanut oil / lecithin / concentrated milk mixture, Volume ratio: 2:0.2:3; Fudan Fuhua Co., Ltd., Shanghai), the administration volume is 5ul / g; the control group is treated with solvent (peanut oil / lecithin / concentrated milk mixture); after 90 days, hematoxylin staining detection, the result showed that the muscle layer of AD mice saw intimal tissue infiltration (such as Figure 5 As shown in B, the ectopic lesion shown by the arrow), indicating that the AD mouse model was successfully established, and this phenomenon was not seen in the control group (such as Figure 5 shown in A).

Embodiment 3

[0051] Embodiment 3 animal experiments

[0052] 1) The uterine weight of AD mice in the IL-22 neutralizing antibody treatment group decreased

[0053] After successful modeling, AD mice (90 days) were continued to be treated with tamoxifen, and the experimental group was intraperitoneally injected with anti-mouse IL-22 neutralizing antibody (5ug / ml, total volume 15ul / g), boosted once every 7 days, After a total of 4 times, the control group was given normal saline treatment, about d120, the mice were treated conventionally, and the weight of the uterus of the mice was weighed. The results showed that the weight of the uterus of AD mice in the IL-22 antibody treatment group was significantly reduced, indicating that IL-22 22 antibody significantly reduced the size of AD mouse uterus as shown in Table 1;

[0054] Table 1: Body weight of mice in each group

[0055] group Rat age (days) Uterine weight (mg) control AD ​​group 120±5 221.98±7.03 AD+α-IL-22...

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Abstract

The invention relates to the technical field of medicines, and in particular to an application of an interleukin (IL-22) antibody in preparing medicines for treating adenomyosis (AD). According to the application provided by the invention, on the basis of research experiments that an angiogenesis promoting effect of endometrial ESC (endometrial stromal cell) of the AD can be inhibited by antagonizing the IL-22 and pathogenesis and progress of the AD can be inhibited subsequently, potential values of antagonizing the IL-22 (such as an IL-22 neutralizing antibody) in treating the AD is further assessed. Based upon results of in vitro experiments and in vivo animal tests, it is displayed that the IL-22 neutralizing antibody, which can take an obvious therapeutic effect on the adenomyosis, can be further used for preparing the medicines for treating the adenomyosis.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a new medicinal application of an interleukin (IL-22) antibody, in particular to the application of the interleukin (IL-22) antibody in preparing medicine for treating adenomyosis. It is found through in vitro experiments and in vivo animal experiments that the IL-22 neutralizing antibody can effectively inhibit the angiogenesis and endometrial proliferation of adenomyosis lesions, and can be further used to prepare a drug for treating adenomyosis. Background technique [0002] According to statistics, adenomyosis (adenomyosis, AD) is a common gynecological disease, and the incidence rate in women of childbearing age is about 8-27%. This disease mostly occurs in women aged 30-50, and about 15% have endometriosis at the same time, and about half have uterine fibroids. In recent years, the incidence of AD has a rising and younger trend. The definition of AD is that endometrial gla...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P15/00
Inventor 金莉萍李明清汪清常凯凯周文洁商文庆
Owner THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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