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Use of acetylcholinesterase inhibitor for preparing diabetes medicines

An acetylcholinesterase and diabetes drug technology, applied in the directions of pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of lactic acidosis, loss of reaction, hypoglycemia, etc., and achieve the effect of improving the symptoms of hyperglycemia

Inactive Publication Date: 2005-12-21
CELL STAR BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] But biguanides have problems with gastrointestinal side effects and lactic acidosis
Among the patients whose initial treatment is effective, 5-10% of patients still lose their response to this drug every year; 2. It causes weight gain, and most obese patients cannot use it; 3. Stimulating insulin secretion can lead to hypoglycemia, and insulin in the blood If the level is too high, it may lead to cardiovascular complications; 4. It is metabolized by the liver, excreted by the kidney and bile, and should be used with caution in patients with liver and kidney insufficiency. Severe renal failure and pregnant women are contraindicated

Method used

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  • Use of acetylcholinesterase inhibitor for preparing diabetes medicines
  • Use of acetylcholinesterase inhibitor for preparing diabetes medicines
  • Use of acetylcholinesterase inhibitor for preparing diabetes medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] The preparation of embodiment 1 diabetes model

[0161] C57BL / 6J mice aged 6-8 weeks were reared routinely. Before injection, STZ was dissolved in 0.1M sodium citrate buffer (PH4.5), and 45 mg / kg was injected intraperitoneally continuously for 5 days. Check your blood sugar twice a week with a Roche blood glucose tester. When the blood glucose concentration is greater than 13.9mM (250mg / ml), it is considered that the diabetes model has been established.

Embodiment 2

[0162] EXAMPLE 2 Expression of AChE in the apoptotic β-cell in the diabetes model in vitro

[0163] 1. STZ can induce RIN-5F cell apoptosis in vitro

[0164] Rat insulinoma cell line RIN-5F was incubated with 1640 medium (15% calf serum, 1.0mM sodium pyruvate, 4.5g / l glucose, 10mM HEPES) at 37°C, 5% CO 2 to cultivate. When the cell growth reached 70% density, after induction with 5mMSTZ, 10mM STZ, 15mM STZ for 24h, the apoptosis was detected by MTT method, flow cytometry and DNA ladder.

[0165] Results: MTT method was used to find that different doses of STZ could reduce the activity of insulinoma cell line RIN-5F ( figure 2 A). 16mM STZ can reduce cell viability to 40%. Flow cytometry also found that with the increase of STZ amount, the rate of apoptosis also increased. Normal cells have about 5% apoptosis rate, and after 24h treatment with 15mM STZ, the apoptosis rate can increase to 52% ( figure 2 B). After inducing RIN-5F cells with 5mM STZ for 24h, it can be fou...

Embodiment 3

[0181] Example 3 Expression of AChE in β-cells of diabetic model mice

[0182] After sacrificing the experimental mice, the pancreas was fixed with 4% paraformaldehyde (PFA) solution at 4°C for 24 hours, then soaked in 30% sucrose solution for 12 hours, embedded with OCT, frozen sections at 10 μM, and stained with acetylcholinesterase.

[0183] Results: In STZ-induced diabetic model islet slices, β-cells had obvious AChE activity. There was no positive staining of AChE in pancreas sections of normal mice ( Figure 5 A). In contrast, with the apoptosis of β-cells and the infiltration of lymphocytes (from day 8 to day 29) in the course of diabetes, specific staining of AChE could be found around the islets ( Figure 5 B-E). Especially when the symptoms of diabetes are severe (from the 22nd day to the 29th day), the destruction of β cells is already quite serious, and the staining of AChE is very strong ( Figure 5 D, E).

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Abstract

The present invention relates to an application of acetylcholinesterase inhibitor for curing diabetes. The described inhibitor includes all the compounds which can inhibit acetylcholinesterase activity and have the action for curing diabetes. The invented experimental results show that these inhibitors have the actions of inhibiting beta-cell death and reducing blood sugar concentration of diabetic model mouse, and can effectively cure or improve diabetes symptom.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of an acetylcholinesterase inhibitor in the preparation of medicines for treating diabetes. Background technique [0002] Diabetes is a group of common metabolic endocrine diseases. It is a chronic disease caused by the absolute lack of insulin or the reduction of the biological effect of insulin. The organization lists diabetes as one of the three difficult diseases. There are 125 million diabetic patients in the world, and the number of diabetic patients in my country has reached 40 million. The prevalence increases with the improvement of people's living standards. The total prevalence rate in 13 regions of China is 0.67%, about 1% in big cities, and the prevalence rate increases significantly after the age of 40. The prevalence rate in European and American countries is 3-6%. Its chronic vascular complications have become one of the important causes of death in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00
Inventor 郭礼和余路阳林波张学军杨磊张宝
Owner CELL STAR BIO TECH
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