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The use of glp-1 receptor agonist drugs

The technology of a receptor agonist and its application is applied in the field of preparing medicines for increasing the immunity of patients, and can solve the problems of destroying the immune function of patients, inconsistent conclusions of anti-cancer effects, and increasing the proliferation of cancer cells.

Active Publication Date: 2022-04-01
赫兰
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, GLP-1 will be rapidly degraded and inactivated by dipeptidyl peptidase IV (DPP-IV) in vivo, and its half-life is less than 2 minutes, so its clinical application is limited.
The use of conventional anticancer drugs after diabetes patients with cancer often leads to exacerbation of diabetes patients
On the one hand, chemotherapy will seriously damage the blood sugar level of the patient. A single radiotherapy and chemotherapy will inhibit and reduce the immune function of the patient, destroy or even destroy the immune function of the patient, and will accelerate the death of the patient in the middle and advanced stages.
And glucocorticoid drugs, widely used to relieve nausea in cancer patients, promote insulin resistance, which contributes to the exacerbation of diabetes
On the other hand, it is well known that although insulin is an important hormone that regulates blood sugar in the body, an excessively high concentration of insulin in the body may increase the proliferation of cancer cells and reduce the apoptosis of cancer cells, thereby promoting the occurrence of malignant tumors
[0007] There are also studies using drugs for the treatment of diabetes, such as exenatide-4, metformin, etc., to treat cancer, but the conclusions on their anticancer effects are very inconsistent. Some articles report that in vitro experiments and nude mouse models, exenatide Peptide-4 can reduce the growth of bowel, breast and prostate cancers (Nomiyama et al., 2014, Koehler and Drucker, 2006, Koehler et al., 2011)

Method used

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  • The use of glp-1 receptor agonist drugs
  • The use of glp-1 receptor agonist drugs
  • The use of glp-1 receptor agonist drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1, Tumorogenicity of CUP-1 Tumor Cell Line in Diabetic Mice

[0115] In order to study the effect of diabetes on HPV16E7-mediated tumorigenesis, HPV-positive cancer cell line (Cup-1) was subcutaneously injected into the neck region of db / db diabetic mice and db / m+ control mice as described above. Similar to the reaction of nude mice, tumor protrusions visible to the naked eye can appear after 3 days. Interestingly, the growth curves of the cancer cell lines in diabetic and control mice were significantly different. Tumor volume in diabetic mice increased six-fold between days 3 and 7 after cancer cell inoculation. Correspondingly, the tumor volume in non-diabetic control mice only expanded by 1.5 times and began to shrink by the seventh day. On day 29, the Cup-1 tumors in the control mice were completely cleared. On day 14, the tumor volume of db / db mice was almost 4 times that of control mice (1256.9±31.4vs 314.4±22.1mm 3 , Pfigure 1 and Table 1 below.

[...

Embodiment 2

[0120] Example 2, Exenatide-4 inhibits tumor growth, while metformin induces tumor growth

[0121] 1) Exenatide-4-induced tumor regression

[0122] according to figure 2 The treatment scheme shown in I, 10-week-old db / db mice bearing CUP-1 tumors, were treated with different doses of exenatide-4. While subcutaneously injecting tumor cells into male diabetic mice and control mice, different concentrations of Exenatide-4 (10 or 30 nM / kg body weight, respectively) or PBS control were subcutaneously injected for 13 days. Such as figure 2 As shown in A, we subcutaneously injected different doses of exenatide-4 into 10-week-old db / db diabetic tumor-bearing mice. After the 13-day administration period, the mice were sacrificed and the tumors were carefully excised and weighed. Store in a deep freezer for subsequent experiments. The area under the curve of tumor volume in diabetic tumor-bearing mice was used as an index.

[0123] In db / db mice, exenatide-4 showed a dose-depende...

Embodiment 3

[0129] Embodiment 3, exenatide-4 and metformin all alleviate hyperglycemia in db / db mice

[0130] The blood glucose levels of the animals in each group in Example 2 above were further measured. Compared with the experimental group treated with PBS, daily administration of 10nM / kg or 30nM / kg exenatide-4 reduced the blood glucose level of db / db mice in a dose-dependent manner ( image 3 A), the dose of 30nM / kg significantly reduced the blood glucose level of db / db mice. Based on the results of an oral glucose tolerance test (OGTT) performed on day 9, the exenatide-4-treated db / db group lowered blood glucose levels below that of the PBS-treated db / db group. Exenatide-4 treatment reduced blood glucose (BG) concentrations at all time points (0, 30, 60 and 120 min) compared to the PBS-treated experimental group (40407.8±9390.8) ( image 3 B and image 3 C), wherein the experimental group treated with 30nM / kg exenatide-4 had the smallest AUC of BG (22268.0±4751.8), followed by the...

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Abstract

The invention relates to the use of a glucagon-like peptide-1 (GLP-1) receptor agonist in the preparation of medicines for treating or preventing tumors suffered by patients; use in medicines. The present invention relates to GLP-1 receptor agonists, especially Exenatide-4 has a regulatory mechanism that significantly increases cytotoxic T cells, reduces regulatory T cells, and finally increases the ratio of cytotoxic T cells / regulatory T cells, And significantly increased the secretion levels of Th1-type inflammatory cytokines IFN-γ and IL-2. Therefore, it can significantly inhibit tumors in patients with immunodeficiency or low blood pressure, especially in patients with type 2 diabetes mellitus. The present invention also relates to the use of the GLP-1 receptor agonist in the preparation of medicines for increasing the immunity of patients.

Description

technical field [0001] The present invention relates to the use of a glucagon-like peptide 1 (GLP-1) receptor agonist for treating or preventing cancer in patients with immunodeficiency diseases. The glucagon-like peptide-1 receptor agonist is used in The use in the preparation of medicines for treating or preventing diabetes associated with cancer, and the use of glucagon-like peptide-1 receptor agonists in the preparation of medicines for increasing the immunity of patients. Background technique [0002] Diabetes is one of the three major diseases that threaten human health. The incidence rate is extremely high, and it is increasing year by year. Its obvious clinical symptoms are that the glucose content in blood and urine exceeds the normal range, accompanied by "three more and one less", that is, eating more, Polydipsia, polyuria and weight loss. Among them, patients with type II diabetes account for more than 90%. For a long time, people have mainly used drugs such as...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/155A61P35/00A61P37/04A61P3/10A61K38/22
CPCA61K45/00A61K31/155A61K38/22A61K2300/00Y02A50/30
Inventor 赫兰
Owner 赫兰
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